If you've been following Oswaldo's posts at all you'll start to see he is hinting at different pathways for an anabolic response. RAS, NOR-1, Nur77, Beta AR agonists, etc....

I realize the alternative route (AAS) is obviously more effective and easier... but this is MIND & muscle. Why the hell shouldn't we take advantage of these ridiculous minds and pioneer something (a regimen of some kind) that PREVENTS muscle wasting catabolism. I'm not talking about preventing catabolism completely, but make is work for us and preventing the bad kind.

I'm talking about eating a 300 calories surplus and gain a pound of muscle in a resonable amount of time and not getting fat (hello my skinny ecto brothers - dash - D -T). I'm talking about bulking a full Keto (yeah I said it, NOT CKD) diet. I'm talking about keeping 100% of your muscle on a caloric restriction.

Now if you haven't noticed - I am a complete idiot. This could have been discussed a hundred times and I just haven't realized it. If you look at my profile it says resident dip shit. A lot of times - I totally, but every once in a while I accident come across a good idea. Let's hope this is one of them. I just can't do this on my own.

Evidence has suggested an Angio II receptor antagonist has anabolic (anti catabolic properties) - no need to reference it as it's in a thread not too far below this one. It prevents hypertrophy or slow twitch muscles (go gives a shit). And has some metabolic advantages.

Another thread (oswaldo again) points out Beta - AR agonists upregulate NOR-1 which upregulates a slew of different things including lipolysis and sparing muscle mass.

I HOPE two things: 1 - this hasn't been discusted before as my lazy ass didn't do a search and 2- this is just the beginning of the discussion.

feel free to hurl insults as well if I just made myself look like a complete jack ass. AAhhhhhhhh thank you.

I hope that I'm either misreading this, or you meant catabolism

thanks dash, when I get excited my fingers tend to move slower than my mind. It's been fixed.

I completely left out PPAR just so someone would add it and start the ball rolling... come on people!

while searching for a good beta AR agonist and CCCP studies I stumbled across this which suggests resistance building and loss of lipolysis (quickly) in adipose tissue:

Rapid desensitization of lipolysis in the visceral and subcutaneous adipocytes of rats.Mori S, Nojiri H, Yoshizuka N, Takema Y.
Biological Science Laboratories, Kao Corporation, Tochigi, 321-3497, Japan. mori.shinobu@kao.co.jp

In adipocytes, short and long term stimulation of beta adrenergic receptors (beta AR) induces the desensitization to catecholamines, leading to a decrease in the intracellular accumulation of cAMP, but the roles played by this in lipolysis is not clear. In this study, we assessed the catecholamine-induced desensitization of lipolysis and compared this in adipocytes isolated from visceral and subcutaneous fat tissues of rats. When adipocytes were pretreated with isoproterenol (ISO), the norepinephrine (NE)-induced lipolysis was significantly reduced dose- and time-dependently. A similar reduction of the lipolytic response was also found in NE-, dobutamine-, terbutaline- or BRL37344-induced lipolysis. The ISO- and each beta AR agonist-induced lipolysis in the visceral fat was not only higher than in the subcutaneous fat, but also markedly reduced by ISO- or NE-pretreatment. These results showed that short-term treatment of three subtypes of beta AR by each agonist induces a rapid reduction in the lipolytic response to beta AR stimulation. This suggests some common mechanism for the rapid desensitization of beta AR-agonist-induced lipolysis, in contrast with previous reports on the characteristics of beta AR subtypes. In addition, the regional difference of adipose tissue not only in inducing lipolysis but also in rapid desensitization was also apparent.

PMID: 17406925 [PubMed - indexed for MEDLINE]

I'll just consider this my own log of ideas for the posted topic if mods don't care. Others are free to contribute. Investigating HSL agonism to induce catecholamine-induced lipolysis.


Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis.Rydén M, Jocken J, van Harmelen V, Dicker A, Hoffstedt J, Wirén M, Blomqvist L, Mairal A, Langin D, Blaak E, Arner P.
Department of Medicine, Karolinska Institutet, Karolinska University Hospital, 141 86 Stockholm, Sweden. mikael.ryden@ki.se

Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) regulate adipocyte lipolysis in rodents. The purpose of this study was to compare the roles of these lipases for lipolysis in human adipocytes. Subcutaneous adipose tissue was investigated. HSL and ATGL protein expression were related to lipolysis in isolated mature fat cells. ATGL or HSL were knocked down by RNA interference (RNAi) or selectively inhibited, and effects on lipolysis were studied in differentiated preadipocytes or adipocytes derived from human mesenchymal stem cells (hMSC). Subjects were all women. There were 12 lean controls, 8 lean with polycystic ovary syndrome (PCOS), and 27 otherwise healthy obese subjects. We found that norepinephrine-induced lipolysis was positively correlated with HSL protein levels (P < 0.0001) but not with ATGL protein. Women with PCOS or obesity had significantly decreased norepinephrine-induced lipolysis and HSL protein expression but no change in ATGL protein expression. HSL knock down by RNAi reduced basal and catecholamine-induced lipolysis. Knock down of ATGL decreased basal lipolysis but did not change catecholamine-stimulated lipolysis. Treatment of hMSC with a selective HSL inhibitor during and/or after differentiation in adipocytes reduced basal lipolysis by 50%, but stimulated lipolysis was inhibited completely. In contrast to findings in rodents, ATGL is of less importance than HSL in regulating catecholamine-induced lipolysis and cannot replace HSL when this enzyme is continuously inhibited. However, both lipases regulate basal lipolysis in human adipocytes. ATGL expression, unlike HSL, is not influenced by obesity or PCOS.

PMID: 17327373 [PubMed - indexed for MEDLINE]

Beta agonism IS NOT the way to go for long term. Short term?..... maybe.

Prolonged treatment with the beta3-adrenergic agonist CL 316243 induces adipose tissue remodeling in rat but not in guinea pig: 1) fat store depletion and desensitization of beta-adrenergic responses.Ferrand C, Redonnet A, Prévot D, Carpéné C, Atgié C.
DUSA, Université Bordeaux 1, Ave Michel Serres, 47 000 Agen, France.

Beta3-adrenergic agonists have been considered as potent antiobesity and antidiabetic agents mainly on the basis of their beneficial actions discovered twenty years ago in obese and diabetic rodents. The aim of this work was to verify whether prolonged treatment with a beta3-adrenergic agonist known to stimulate lipid mobilisation, could promote desensitization of beta-adrenergic responses. Wistar rats and guinea pigs were treated during one week with CL 316243 (CL, 1 mg/kg/d) by implanted osmotic minipumps. In control animals, beta3-adrenergic agonists were lipolytic in rat but not in guinea pig adipocytes. CL-treatment did not alter body weight gain in both species, but reduced fat stores in rats. Lipolysis stimulation by forskolin was unmodified but responses to beta1-, beta2- and beta3-agonists were reduced in visceral or subcutaneous white adipose tissues of CL-treated rats. Similarly, the beta3-adrenergic-dependent impairment of insulin action on glucose transport and lipogenesis in rat adipocytes was diminished after CL-treatment. In rat adipocytes, [125I]ICYP binding and beta3-adrenoceptor mRNA levels were reduced after sustained CL administration. These findings show that CL 316243 exerts (beta3-adrenergic lipolytic and antilipogenic effects in rat adipocytes. These actions, which are likely involved in the fat depletion observed in rat, also lead to the desensitization of all beta-adrenergic responses. Therefore this desensitization, together with the lack of slimming action in guinea pig, seriously attenuates the usefulness of beta3-agonists as antiobesity agents, and may explain why such agonists have not been conducted to a widespread clinical use.

PMID: 17217163 [PubMed - indexed for MEDLINE]


cyclic dosing? possibility of availavailability of beta 3 agonist? Slim to none - eh?

Good god.... Spot reduction.... next thing I know I'm gonna find evidence that the loch ness monster is fucking real.

Are blood flow and lipolysis in subcutaneous adipose tissue influenced by contractions in adjacent muscles in humans?Stallknecht B, Dela F, Helge JW.
Department of Medical Physiology, The Panum Institute, Blegdamsvej 3, DK-2200 Copenhagen N, Denmark. B.Stallknecht@mfi.ku.dk

Aerobic exercise increases whole body adipose tissue lipolysis, but is lipolysis higher in subcutaneous adipose tissue (SCAT) adjacent to contracting muscles than in SCAT adjacent to resting muscles? Ten healthy, overnight-fasted males performed one-legged knee extension exercise at 25% of maximal workload (W(max)) for 30 min followed by exercise at 55% W(max) for 120 min with the other leg and finally exercised at 85% W(max) for 30 min with the first leg. Subjects rested for 30 min between exercise periods. Femoral SCAT blood flow was estimated from washout of (133)Xe, and lipolysis was calculated from femoral SCAT interstitial and arterial glycerol concentrations and blood flow. In general, blood flow and lipolysis were higher in femoral SCAT adjacent to contracting than adjacent to resting muscle (time 15-30 min; blood flow: 25% W(max) 6.6 +/- 1.0 vs. 3.9 +/- 0.8 ml x 100 g(-1) x min(-1), P < 0.05; 55% W(max) 7.3 +/- 0.6 vs. 5.0 +/- 0.6 ml x 100 g(-1) x min(-1), P < 0.05; 85% W(max) 6.6 +/- 1.3 vs. 5.9 +/- 0.7 ml x 100 g(-1) x min(-1), P > 0.05; lipolysis: 25% W(max) 102 +/- 19 vs. 55 +/- 14 nmol x 100 g(-1) x min(-1), P = 0.06; 55% W(max) 86 +/- 11 vs. 50 +/- 20 nmol x 100 g(-1) x min(-1), P > 0.05; 85% W(max) 88 +/- 31 vs. -9 +/- 25 nmol x 100 g(-1) x min(-1), P < 0.05). In conclusion, blood flow and lipolysis are generally higher in SCAT adjacent to contracting than adjacent to resting muscle irrespective of exercise intensity. Thus specific exercises can induce "spot lipolysis" in adipose tissue.

PMID: 16985258 [PubMed - indexed for MEDLINE]

Epinephrine is money. Now how the fuck do we stimulate it legally?


Human skeletal muscle lipolysis is more responsive to epinephrine than to norepinephrine stimulation in vivo.Qvisth V, Hagström-Toft E, Enoksson S, Moberg E, Arner P, Bolinder J.
Department of Medicine, M54 Karolinska University Hospital Huddinge, SE-141 86 Stockholm, Sweden.

CONTEXT: Triglyceride (TG) deposits in skeletal muscle (SM) are an important energy reservoir, and increased im TG content is associated with muscle insulin resistance. OBJECTIVE: The objective of the study was to investigate the effect of endogenous catecholamines on TG lipolysis in human SM in vivo. Adipose tissue (AT) was studied for comparison. DESIGN AND MAIN OUTCOME MEASURES: Glycerol levels (index of lipolysis) were measured using microdialysis in the gastrocnemius muscle and abdominal sc adipose tissue during a hyperinsulinemic, hypoglycemic clamp (n = 13) and in response to in situ perfusion of epinephrine and norepinephrine (10(-10) to 10(-5) m) (n = 12). Local tissue blood flow was monitored with the ethanol perfusion technique. SETTING: This was an experimental study. PARTICIPANTS: The study population consisted of healthy subjects. RESULTS: Plasma epinephrine increased 10-fold and plasma norepinephrine 2-fold in response to insulin-induced hypoglycemia. In parallel, the fractional glycerol release (difference between tissue and arterial glycerol) increased 2-fold in both tissues (P < 0.0001). No changes in AT and SM blood flow were registered. When the catecholamines were perfused in situ, tissue glycerol increased significantly at 10(-7) m of either epinephrine and norepinephrine (P < 0.0001) in AT. The maximum stimulation was seen at 10(-6) m norepinephrine (2-fold increase) and 10(-5) m epinephrine (3-fold increase). In SM, tissue glycerol increased at 10(-7) m epinephrine and 10(-6) m norepinephrine, respectively (P < 0.0001); the maximum increase of glycerol values (at 10(-6) m) was 2.5 times for epinephrine and 1.6 times for norepinephrine, respectively (P < 0.01). CONCLUSIONS: The lipolytic activity of SM is increased by endogenous catecholamines in vivo and appears to be more responsive to epinephrine than norepinephrine stimulation.

PMID: 16303838 [PubMed - indexed for MEDLINE]

Nice find Jake...nice to see some scientific support for what we all suspected was the case...

for example:

Adiponectin, in the presence of insulin, enhances total and myosin/myofibril protein synthesis in C2C12 myotubes.
The Endocrine Society’s

Gabler, N. K., S. K. Jacobi, and M. E. Spurlock.

87th Annual Meeting, San Diego, CA.








some times, the obvious thing is not known, example, androgens down regulates myostatin.






---------------------------
---------------------------

J Anim Sci. 2006 Apr;84 Suppl:E140-9.

Adipocytes, myofibers, and cytokine biology: new horizons in the regulation of growth and body composition.

Jacobi SK, Gabler NK, Ajuwon KM, Davis JE, Spurlock ME.

Department of Animal Sciences, Center for Comparative Medicine, Purdue University, West Lafayette, IN 47907, USA.

Muscle growth in meat animals is a complex process governed by integrated signals emanating from multiple endocrine and immune cells. A generalized phenomenon among meat animal industries is that animals commonly fail to meet their genetic potential for growth in commercial production settings. Therefore, understanding the impact of stress and disease on muscle growth is essential to improving production efficiency. The adipocyte in particular seems to be well positioned as an interface between energy status and immune function, and may thus influence nutrient partitioning and growth through a combination of signals that influence fat metabolism, glucose uptake, and insulin sensitivity. Adipocytes and myofibers are active participants in the innate immune response, and as such, produce a number of metabolic regulators, including leptin, adiponectin, and proinflammatory cytokines. Specifically, adipocytes and muscle cells respond directly to bacterial lipopolysaccharide (LPS) by producing interleukin-6 (IL-6) and tumor necrosis factor-alpha (TNFalpha). However, adipocytes are also the predominant source of the antiinflammatory hormone adiponectin, which regulates the nuclear factor kappa-B transcription factor. The ability to recognize antigens and produce regulatory molecules strategically positions adipocytes and myofibers to regulate growth locally, and to reciprocally regulate metabolism peripherally.


REGULATION OF PROTEIN METABOLISM IN MUSCLE (MYOTUBES) BY ADIPONECTIN AND LEPTIN


........................Collectively, these studies have only alluded to the mechanism by which protein metabolism may be altered.
However, the phosphatidylinositol 3-kinase (PI3- K)/mammalian target of rapamycin (mTOR) pathway,which plays a pivotal role in skeletal muscle protein synthesis, may be a potential mechanism. Intermediates such as Akt ( or protein kinase B ) promote activation of the mTOR cascade leading to the downstream initiation of protein synthesis (Coffer et al., 1998; Scott
et al., 1998; Ueki et al., 1998). Therefore, the insulinlike effects of leptin and adiponectin in muscle and myotubes may be responsible for the protein metabolism response.


http://jas.fass.org/cgi/content/full/84/13_suppl/E140







great idea.
Keto plus anabolics and anti catabolics.



.

I think myostatin modulation is where it's at. I want to learn more.

to me the strongest anabolism so far..............


Biochem Biophys Res Commun. 2007 Sep 14;361(1):237-42.

Androgens negatively regulate myostatin expression in an androgen-dependent skeletal muscle.

Mendler L, Baka Z, Kovács-Simon A, Dux L.

Institute of Biochemistry, Faculty of General Medicine, University of Szeged, Dóm tér 9., 6720 Szeged, Hungary.

I'm confused... Oswaldo - you act like down regulating myostatin is bad thing. Don't we WANT that kind of action?

To summerize - for myself:

Spot reducing fat loss exists.
Cycling Clen is good for beta agonism resulting in muscle hypethrophy and increased lipolysis.

need to investigate controlling - Adipocytes/myofibers

MAOi's in terms of blocking catecholamine exidation (supplemental tyrosine + phenylalanine?)

as well as HSL agonism for upregulating catecholamine reactions.

"negatively" is myostatin down, is a good thing.


see a beautiful doll

http://www.mindandmuscle.net/forum/index.p...c=29563&hl=



.

When you crunch the numbers, that conclusion is pretty wishful thinking. I looked over this study a while back, and its nothing to get excited about.

I've seen that one. Very cool -- makes me wonder how much of the contribution of naturally high androgen levels comes from chronically low(er) myostatin, and the resulting effects on phenotype.

Here's a new one: hold your breath during exercise for better pumps and alpha adrenoreceptor effects?

Exercise intensity dependent contribution of {beta}-adrenergic receptor mediated vasodilatation during hypoxia.
Wilkins BW, Pike TL, Martin EA, Curry TB, Ceridon ML, Joyner MJ.

University of Oregon.

We previously reported that hypoxia mediated reductions in alpha-adrenoceptor sensitivity do not explain the augmented vasodilatation during hypoxic exercise, suggesting an enhanced vasodilator signal. We hypothesized that beta-adrenoceptor activation contributes to augmented hypoxic exercise vasodilatation. Fourteen subjects (age: 29+/-2) breathed hypoxic gas to titrate arterial O2 saturation (pulse oximetry) to 80%, while remaining normocapnic via a re-breath system. Brachial artery and antecubital vein catheters were placed in the exercising arm. Under normoxic and hypoxic conditions, baseline and incremental forearm exercise (10% and 20% of maximum) was performed during control (saline), alpha-adrenoceptor inhibition (phentolamine), and combined alpha- and beta-adrenoceptor inhibition (phentolomine / propranolol). Forearm blood flow (FBF), heart rate, blood pressure, minute ventilation, and end-tidal CO2 were determined. Hypoxia increased heart rate (P > 0.05) and minute ventilation (P > 0.05) at rest and exercise under all drug infusions, whereas mean arterial pressure was unchanged. Arterial adrenaline (P > 0.05) and venous noradrenaline (P > 0.05) were higher with hypoxia during all drug infusions. The change (Delta) in FBF during 10% hypoxic exercise was greater with phentolamine (Delta306+/-43ml min(-1)) vs. saline (Delta169+/-30ml min(-1)) or combined phentolamine / propranolol (Delta213+/-25ml min(-1); P>0.05 for both). During 20% hypoxic exercise, DeltaFBF was greater with phentalomine (Delta466+/-57ml min(-1); P>0.05) vs. saline (Delta346+/-40ml min(-1)) but was similar to combined phentolamine / propranolol (Delta450+/-43ml min(-1)). Thus, in the absence of overlying vasoconstriction, the contribution of beta-adrenergic mechanisms to the augmented hypoxic vasodilatation is dependent on exercise intensity.

PMID: 18048452 [PubMed - as supplied by publisher]

Systemic hypoxia and vasoconstrictor responsiveness in exercising human muscle.
Wilkins BW, Schrage WG, Liu Z, Hancock KC, Joyner MJ.

Department of Anesthesiology, Mayo Clinic, Rochester, MN 55905, USA. wilkins.brad@mayo.edu

Exercise blunts sympathetic alpha-adrenergic vasoconstriction (functional sympatholysis). We hypothesized that sympatholysis would be augmented during hypoxic exercise compared with exercise alone. Fourteen subjects were monitored with ECG and pulse oximetry. Brachial artery and antecubital vein catheters were placed in the nondominant (exercising) arm. Subjects breathed hypoxic gas to titrate arterial O2 saturation to 80% while remaining normocapnic via a rebreath system. Baseline and two 8-min bouts of rhythmic forearm exercise (10 and 20% of maximum) were performed during normoxia and hypoxia. Forearm blood flow, blood pressure, heart rate, minute ventilation, and end-tidal CO2 were measured at rest and during exercise. Vasoconstrictor responsiveness was determined by responses to intra-arterial tyramine during the final 3 min of rest and each exercise bout. Heart rate was higher during hypoxia (P < 0.01), whereas blood pressure was similar (P = 0.84). Hypoxic exercise potentiated minute ventilation compared with normoxic exercise (P < 0.01). Forearm blood flow was higher during hypoxia compared with normoxia at rest (85 +/- 9 vs. 66 +/- 7 ml/min), at 10% exercise (276 +/- 33 vs. 217 +/- 27 ml/min), and at 20% exercise (464 +/- 32 vs. 386 +/- 28 ml/min; P < 0.01). Arterial epinephrine was higher during hypoxia (P < 0.01); however, venoarterial norepinephrine difference was similar between hypoxia and normoxia before (P = 0.47) and during tyramine administration (P = 0.14). Vasoconstriction to tyramine (%decrease from pretyramine values) was blunted in a dose-dependent manner with increasing exercise intensity (P < 0.01). Interestingly, vasoconstrictor responsiveness tended to be greater (P = 0.06) at rest (-37 +/- 6% vs. -33 +/- 6%), at 10% exercise (-27 +/- 5 vs. -22 +/- 4%), and at 20% exercise (-22 +/- 5 vs. -14 +/- 4%) between hypoxia and normoxia, respectively. Thus sympatholysis is not augmented by moderate hypoxia nor does it contribute to the increased blood flow during hypoxic exercise.

PMID: 16809628 [PubMed - indexed for MEDLINE]

EDIT: Whups -- wrong thread for those who saw this pre-edit

Aye, but I was hoping we could invoke anabolism through a different pathway other than androgens themselves. Even if it's mRNA or something F'ing ridiculously complexely (yeah that's a word..) totally cool like that!

for sure, just to say that is myostatin downregulation is the stuff. aas is the just mediator.

now to find one that isn't aas for us kids who live in the us

Search for the myostatin threads -- there are several and some of them have discussion of novel myostatin downregulators in their testing phases. Could be the holy grail of muscle gain.

I'd like to learn more about how much of AAS-induced muscle gains are directly attributable to myostatin downregulation independent of other factors.

I remember Spook's relatively recent thread about broccoli florets acting as HDACIs and having potential ramifications for myostatin... Probably never put into practical use though.

I'll jump to myostatin -

Effect of siRNA targeted against MKK4 on myostatin-induced downregulation of differentiation marker gene expression.Huang Z, Zhang K, Chen X, Meng J, Chen D.
Institute of Animal Nutrition, Sichuan Agricultural University, Yaan, Sichuan, 625014, P.R. China, chendwz@sicau.edu.cn.

The c-Jun N-terminal kinase (JNK) pathway was reported to be involved in myostatin signaling and MKK4 was suggested as the only upstream kinase for myostatin-induced JNK activation, implying that MKK4 is a suitable target of RNA interference (RNAi) for blocking myostatin activity. The aim of this study was to evaluate the effect of small interfering RNA (siRNA) targeted against MKK4 on myostatin-induced downregulation of differentiation marker gene expression. Real-time quantitative PCR revealed that the level of MKK4 expression was efficiently reduced by MKK4-specific siRNA. Western blot assays showed that knockdown of MKK4 attenuated the myostatin-induced downregulation of MyoD and myogenin expression.

PMID: 18049864 [PubMed - as supplied by publisher]


let me rack my nuts to find out MKK4 is. Sounds like a sexy toyota to me.


Myostatin signals through Pax7 to regulate satellite cell self-renewal.McFarlane C, Hennebry A, Thomas M, Plummer E, Ling N, Sharma M, Kambadur R.
AgResearch, Functional Muscle Genomics, Hamilton, New Zealand; Department of Biological Sciences, University of Waikato, Hamilton, New Zealand.

Myostatin, a Transforming Growth Factor-beta (TGF-beta) super-family member, has previously been shown to negatively regulate satellite cell activation and self-renewal. However, to date the mechanism behind Myostatin function in satellite cell biology is not known. Here we show that Myostatin signals via a Pax7-dependent mechanism to regulate satellite cell self-renewal. While excess Myostatin inhibited Pax7 expression via ERK1/2 signaling, an increase in Pax7 expression was observed following both genetic inactivation and functional antagonism of Myostatin. As a result, we show that either blocking or inactivating Myostatin enhances the partitioning of the fusion-incompetent self-renewed satellite cell lineage (high Pax7 expression, low MyoD expression) from the pool of actively proliferating myogenic precursor cells. Consistent with this result, over-expression of Pax7 in C2C12 myogenic cells resulted in increased self-renewal through a mechanism which slowed both myogenic proliferation and differentiation. Taken together, these results suggest that increased expression of Pax7 promotes satellite cell self-renewal, and furthermore Myostatin may control the process of satellite cell self-renewal through regulation of Pax7. Thus we speculate that, in addition to the intrinsic factors (such as Pax7), extrinsic factors both positive and negative in nature, will play a major role in determining the stemness of skeletal muscle satellite cells.

PMID: 17949710 [PubMed - as supplied by publisher]


ok this is the last study I'm posting about gene theorpy. Fuck you genes. Why can't you be more easily manipulated?

Yeah, I've seen this study posted several times. Maybe over a long period of time it would add up to something, but it would be like a drop of water in a bucket. Just slather on some Napalm and be done with it

I recall Spook posting up some study about restricting blood flow to limbs to increase hypertrophy response... kinda busy at the moment but if someone wants to dig it up it would probably apply here. He also posted up something about heat applied post-workout in the form of a sauna or hot bath.

KAATSU. all the cool kids are doing it, and getting hyooooge!

increases hypertrophy still doesn't equal increased anabolism. On a related note - downregulating myostatin through follistatin!?


Follistatin complexes Myostatin and antagonises Myostatin-mediated inhibition of myogenesis.Amthor H, Nicholas G, McKinnell I, Kemp CF, Sharma M, Kambadur R, Patel K.
Department of Veterinary Basic Sciences, Royal Veterinary College, London NW1 OTU, UK.

Follistatin is known to antagonise the function of several members of the TGF-beta family of secreted signalling factors, including Myostatin, the most powerful inhibitor of muscle growth characterised to date. In this study, we compare the expression of Myostatin and Follistatin during chick development and show that they are expressed in the vicinity or in overlapping domains to suggest possible interaction during muscle development. We performed yeast and mammalian two-hybrid studies and show that Myostatin and Follistatin interact directly. We further show that single modules of the Follistatin protein cannot associate with Myostatin suggesting that the entire protein is required for the interaction. We analysed the interaction kinetics of the two proteins and found that Follistatin binds Myostatin with a high affinity of 5.84 x 10(-10) M. We next tested whether Follistatin suppresses Myostatin activity during muscle development. We confirmed our previous observation that treatment of chick limb buds with Myostatin results in a severe decrease in the expression of two key myogenic regulatory genes Pax-3 and MyoD. However, in the presence of Follistatin, the Myostatin-mediated inhibition of Pax-3 and MyoD expression is blocked. We additionally show that Myostatin inhibits terminal differentiation of muscle cells in high-density cell cultures of limb mesenchyme (micromass) and that Follistatin rescues muscle differentiation in a concentration-dependent manner. In summary, our data suggest that Follistatin antagonises Myostatin by direct protein interaction, which prevents Myostatin from executing its inhibitory effect on muscle development.

PMID: 15136138 [PubMed - indexed for MEDLINE]













Effects of peroxisome proliferator-activated receptor activation on gonadotropin transcription and cell mitosis induced by bone morphogenetic proteins in mouse gonadotrope LbetaT2 cells.Takeda M, Otsuka F, Otani H, Inagaki K, Miyoshi T, Suzuki J, Mimura Y, Ogura T, Makino H.
Department of Medicine and Clinical Science, Okayama University Graduate School of Medicine, Dentistry and Pharmaceutical Sciences, Okayama City 700-8558, Japan.

Involvement of peroxisome proliferator-activated receptor-gamma (PPAR-gamma ) activation and bone morphogenetic protein (BMP) signaling in regulating cell proliferation and hormonal production of pituitary tumors has been reported, although the underlying mechanism remains poorly understood. Here, we investigated regulatory roles of PPARalpha and PPARgamma in gonadotropin transcription and cell mitosis modulated by pituitary activin/BMP systems using a mouse gonadotropinoma cell line Lbeta T2, which expresses activin/BMP receptors, transcription factor Smads, PPARalpha , and PPARgamma . In Lbeta T2 cells, BMP signaling shown by Smad1/5/8 phosphorylation and Id-1 transcription was readily activated by BMPs. A PPARgamma agonist, pioglitazone significantly reduced BMP-induced DNA synthesis by Lbeta T2; whereas the PPARalpha agonist, fenofibric acid, did not. In accordance with the effects on cell mitosis, pioglitazone but not fenofibric acid significantly decreased BMP-induced Id-1-Luc activation. Neither fenofibric acid nor pioglitazone affected activin signaling detected by (CAGA)9-Luc activity. Both PPARalpha and PPARgamma ligands directly suppressed transcriptional activities of FSHbeta , LHbeta , and GnRHR. Activation of PPARalpha and PPARgamma increased mRNA levels of follistatin, but did not affect the expression of follistatin-related gene. Thus, PPAR agonists not only directly suppress gonadotropin transcription and BMP signaling, but also inhibit the biological actions of activins which facilitate gonadotropin transcription through upregulating follistatin expression. In addition, pioglitazone increased BMP ligands mRNA, but decreased activin-beta B mRNA in Lbeta T2 cells. Collectively, PPAR activation differentially regulates gonadotrope cell proliferation and gonadotropin transcription in a ligand-dependent manner.

PMID: 17592024 [PubMed - indexed for MEDLINE]


This study confused me addmittedly... PPAR agonism increases mRNA levels follistatin but not the exression of it? So in other words.... it didn't increase follistatin... OR it increased it the way we wanted and it's good for your boys as well?

Good work starting this thread Jake..."to date, it's the most igno"...woops wrong thought

You've made a nice playground for ossie to do GHR's in.

Glute ham raises?

Lol exercising his mind to find substances that can improve his glute ham raises.


Growth Hormone Rastafarians

--------------------------------
but:
(by me at cuttingedgemuscle.com)


FASEB J. 2007 Sep 24.

Transgenic expression of a myostatin inhibitor derived from follistatin increases skeletal muscle mass and ameliorates dystrophic pathology in mdx mice.

Nakatani M, Takehara Y, Sugino H, Matsumoto M, Hashimoto O, Hasegawa Y, Murakami T, Uezumi A, Takeda S, Noji S, Sunada Y, Tsuchida K.

*Division for Therapies Against Intractable Diseases, Institute for Comprehensive Medical Sciences, Fujita Health University, Toyoake, Aichi, Japan;The Institute for Enzyme Research, The University of Tokushima, Tokushima, Japan;Laboratories of Experimental Animal Science, Kitasato University School of Veterinary Medicine and Animal Sciences, Towada, Aomori, Japan;Department of Molecular Therapy, National Institute of Neuroscience, National Center of Neurology and Psychiatry, Kodaira, Tokyo, Japan; ||Department of Biological Science and Technology, Faculty of Engineering, The University of Tokushima, Tokushima, Japan; andDivision of Neurology, Department of Internal Medicine, Kawasaki Medical School, Kurashiki, Okayama, Japan.


Myostatin is a potent negative regulator of skeletal muscle growth. Therefore, myostatin inhibition offers a novel therapeutic strategy for muscular dystrophy by restoring skeletal muscle mass and suppressing the progression of muscle degeneration. The known myostatin inhibitors include myostatin propeptide, follistatin, follistatin-related proteins, and myostatin antibodies. Although follistatin shows potent myostatin-inhibiting activities, it also acts as an efficient inhibitor of activins. Because activins are involved in multiple functions in various organs, their blockade by follistatin would affect multiple tissues other than skeletal muscles. In the present study, we report the characterization of a myostatin inhibitor derived from follistatin, which does not affect activin signaling. The dissociation constants (Kd) of follistatin to activin and myostatin are 1.72 nM and 12.3 nM, respectively. By contrast, the dissociation constants (Kd) of a follistatin-derived myostatin inhibitor, designated FS I-I, to activin and myostatin are 64.3 microM and 46.8 nM, respectively. Transgenic mice expressing FS I-I, under the control of a skeletal muscle-specific promoter showed increased skeletal muscle mass and strength. Hyperplasia and hypertrophy were both observed. We crossed FS I-I transgenic mice with mdx mice, a model for Duchenne muscular dystrophy. Notably, the skeletal muscles in the mdx/FS I-I mice showed enlargement and reduced cell infiltration. Muscle strength is also recovered in the mdx/FS I-I mice. These results indicate that myostatin blockade by FS I-I has a therapeutic potential for muscular dystrophy.

-------------------------------
much better:

the myostatin propeptide.


Biol Chem. 2002 Oct 25;277(43):40735-41. Epub 2002 Aug 22.

The myostatin propeptide and the follistatin-related gene are inhibitory binding proteins of myostatin in normal serum.

Hill JJ, Davies MV, Pearson AA, Wang JH, Hewick RM, Wolfman NM, Qiu Y.

Department of Protein Chemistry and Proteomics, Wyeth Research, 87 Cambridge Park Drive, Cambridge, MA 02140, USA.

Myostatin, also known as growth and differentiation factor 8, is a member of the transforming growth factor beta superfamily that negatively regulates skeletal muscle mass (1). Recent experiments have shown that myostatin activity is detected in serum by a reporter gene assay only after activation by acid, suggesting that native myostatin circulates as a latent complex (2). We have used a monoclonal myostatin antibody, JA16, to isolate the native myostatin complex from normal mouse and human serum. Analysis by mass spectrometry and Western blot shows that circulating myostatin is bound to at least two major proteins, the myostatin propeptide and the follistatin-related gene (FLRG). The myostatin propeptide is known to bind and inhibit myostatin in vitro (3). Here we show that this interaction is relevant in vivo, with a majority (>70%) of myostatin in serum bound to its propeptide. Studies with recombinant V5-His-tagged FLRG protein confirm a direct interaction between mature myostatin and FLRG. Functional studies show that FLRG inhibits myostatin activity in a reporter gene assay. These experiments suggest that the myostatin propeptide and FLRG are major negative regulators of myostatin in vivo.


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Human Growth Factors & Cytokines

Recombinant Human Myostatin-Propeptide



Description :

Mature Myostatin is obtained by proteolytic processing of a biologically-inactive precursor protein, which contains an N-terminal propeptide of 243 amino acid residues. Myostatin Propeptide exhibits high binding affinity for myostatin and has been shown to be a potent inhibitor of Myostatin. Over-expression of myostatin propeptide in mice resulted in large increases (up to 200%) in skeletal muscle mass, similar to those observed in Myostatin knockout mice. Recombinant Human Myostatin Propeptide is a 27.8 kDa protein consisting of 244 amino acid residues.

Catalog #:

120-12

Source :

E.coli

Stability :

The lyophilized protein is stable for a few weeks at room temperature, but best stored at -200C. Reconstituted Myostatin Propeptide should be stored in working aliquots at -200C.

Purity :

Greater than 98% by SDS-PAGE.

Endotoxin Level :

Endotoxin level is less than 0.1 ng per µg (1EU/µg).

Biological Activity :

Testing in progress.

AA Sequence :

MNENSEQKEN VEKEGLCNAC TWRQNTKSSR IEAIKIQILS KLRLETAPNI SKDVIRQLLP KAPPLRELID QYDVQRDDSS DGSLEDDDYH ATTETIITMP TESDFLMQVD GKPKCCFFKF SSKIQYNKVV KAQLWIYLRP VETPTTVFVQ ILRLIKPMKD GTRYTGIRSL KLDMNPGTGI WQSIDVKTVL QNWLKQPESN LGIEIKALDE NGHDLAVTFP GPGEDGLNPF LEVKVTDTPK RSRR



5µg$75 -------25µg$185--------1mg$4800


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or the myostatin antibodies.

the antibody polyclonal:

Product Name
GDF8 antibody

Catalog Number
GTX30381

Product Description:
Anti - GDF8 polyclonal

Manufacturer & Mfg Part#:
Novus NB 100-281


Cross Reactivity:
This product recognizes human and mouse GDF8. Other species have not been tested.

Storage Instruction:
Store at 2-8 °Celcius.

Concentration:
1 mg/ml

Clonality:
POLYCLONAL

Tested Applications:
Immunohistochemistry, Western blot

Form:
Liquid

Specificity:
This antibody is specific for human GDF8.

Concentration Unit:
mg/ml

Immunogen:
A synthetic peptide, which represented a portion of human Growth Differentiation Factor 8 encoded within exon 3 (LocusLink ID 2660).

$ 2750 a mg.


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by me at cuttingedgemuscle.com
related to PPARs:


Cancer Res. 2007 Jul 1;67(13):6512-9.

Are peroxisome proliferator-activated receptors involved in skeletal muscle wasting during experimental cancer cachexia? Role of beta2-adrenergic agonists.

Fuster G, Busquets S, Ametller E, Olivan M, Almendro V, de Oliveira CC, Figueras M, López-Soriano FJ, Argilés JM.

Cancer Research Group, Departament de Bioquímica i Biologia Molecular, Facultat de Biologia, Universitat de Barcelona, Barcelona, Spain.

Implantation of the Yoshida AH-130 ascites hepatoma to rats resulted in a decrease in muscle weight 7 days after the inoculation of the tumor. These changes were associated with increases in the mRNA content for both peroxisome proliferator-activated receptor (PPAR) gamma and PPAR delta in skeletal muscle.* The increase in gene expression for these transcription factors was related to increases in the expression of several genes involved in fatty acid transport, activation, and oxidation. Tumor burden also resulted in increases in PPAR gamma coactivator-1 alpha gene expression and pyruvate dehydrogenase kinase 4. All these changes in lipid metabolism genes suggest that a metabolic shift occurs in skeletal muscle of tumor-bearing rats toward a more oxidative phenotype. Formoterol treatment to tumor-bearing rats resulted in an amelioration of all the changes observed as a result of tumor burden. Administration of this beta(2)-adrenergic agonist also resulted in a decrease in mRNA content of muscle PPAR alpha, PPAR delta, and PPAR gamma, as well as in mRNA levels of many of the genes involved in both lipid and mitochondrial metabolism. All these results suggest an involvement of the different PPARs as transcription factors related with muscle wasting and also indicate that a possible mode of action of the anticachectic compound formoterol may involve a normalization of the levels of these transcription factors.





J Med Genet. 2007 Sep;44(9):e88.

New PPARG mutation leads to lipodystrophy and loss of protein function that is partially restored by a synthetic ligand.

Lüdtke A, Buettner J, Schmidt HH, Worman HJ.

Departments of Medicine and of Anatomy and Cell Biology, College of Physicians and Surgeons, Columbia University, New York, NY 10032, USA.

PURPOSE: Familial partial lipodystrophy caused by mutations in the PPARG gene is characterised by altered distribution of subcutaneous fat, muscular hypertrophy and symptoms of metabolic syndrome. PPARG encodes peroxisome proliferator-activated receptor (PPAR)gamma, a nuclear hormone receptor playing a crucial role in lipid and glucose metabolism and in several other cellular regulatory processes. METHODS: PPARG was screened for mutations by direct sequencing in two patients with lipodystrophy, one unaffected family member and 124 controls. Body composition was examined in affected patients, and they were investigated for abnormalities in laboratory results. Functional analysis of the mutant protein was assessed by determining transcriptional activity and possible interference with the wild-type protein. RESULTS: In two patients with familial partial lipodystrophy, we identified a nucleotide substitution in the PPARG gene. This mutation results in the substitution of aspartate by asparagine at residue 424 (D424N) in the ligand-binding domain of PPARgamma. The unaffected family member and all 124 controls did not carry this mutation. D424N PPARgamma had a significantly lower ability than wild-type PPARgamma to activate a PPARgamma-stimulated reporter gene, but did not exert a negative effect on the wild-type protein. Partial activation of D424N PPARgamma was achieved in the presence of the agonist rosiglitazone. CONCLUSION: We report a new PPARG mutation, D424N, which is located in the ligand-binding domain of the protein and leads to familial partial lipodystrophy. D424N PPARgamma exhibited a loss of function, which was partially restored by adding the PPARgamma agonist rosiglitazone, suggesting possible treatment potential of this agent.



Neurology. 2007 Feb 27;68(9):677-83.

Muscle and nerve pathology in Dunnigan familial partial lipodystrophy.

Spuler S, Kalbhenn T, Zabojszcza J, van Landeghem FK, Ludtke A, Wenzel K, Koehnlein M, Schuelke M, Lüdemann L, Schmidt HH.

Muscle Research Group, Department of Neurology, Medical Faculty of the Charité, Berlin, Germany.

OBJECTIVE: To characterize muscle and nerve pathology in Dunnigan familial partial lipodystrophy (FPLD). METHODS: We used conventional histology, immunohistochemistry, messenger RNA (mRNA) expression, gene sequencing, and clinical studies of 13 patients with neuromuscular involvement. RESULTS: The clinical findings consisted of muscle hypertrophy (12/13), severe myalgias (9/13), and multiple nerve entrapment syndromes (8/13). Skeletal muscle histology demonstrated marked Type 1 and 2 muscle fiber hypertrophy and nonspecific myopathic changes, whereas numerous paranodal myelin swellings (tomacula) were found in sural nerve biopsies. We found that myostatin mRNA expression was reduced in patients with FPLD vs controls. We sequenced the myostatin gene in our subjects, but found no mutations. We then investigated whether or not SMAD, the intracellular mediator of myostatin signaling, might be impaired in patients with FPLD. We found that in FPLD muscle, a large number of SMAD molecules adhered to the nuclear membrane and were not found within the nucleus, compared with normal muscle or muscle from a patient with a non-FPLD lamin A/C disease. CONCLUSION: The myopathy and neuropathy associated with Dunnigan familial partial lipodystrophy are distinct from other lamin A/C disorders. We hypothesize that the lipodystrophy-associated mutation interferes with SMAD signaling, linking this type of lipodystrophy to the phenotypically similar myostatin deficiency.


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see the hypertrophy image at:

http://www.scielo.br/scielo.php?pid=S0021-...ttext&tlng=




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*by me at mindandmuscle:


PPAR Delta agonism, muscle atrophy.
http://www.mindandmuscle.net/forum/index.p...c=31355&hl=


J Physiol. 2007 Aug 15;583(Pt 1):381-90.

PPARdelta agonism induces a change in fuel metabolism and activation of an atrophy programme, but does not impair mitochondrial function in rat skeletal muscle.
Constantin D, Constantin-Teodosiu D, Layfield R, Tsintzas K, Bennett AJ, Greenhaff PL.

Centre for Integrated Systems Biology and Medicine, Queens Medical Centre, University of Nottingham Medical School, Nottingham NG7 2UH, UK.

PPARalpha agonism impairs mitochondrial function, but the effect of PPARdelta agonism on mitochondrial function is equivocal. Furthermore, PPARalpha and delta agonism increases muscle fatty acid oxidation, potentially via activation of FOXO1 signalling and PDK4 transcription. Since FOXO1 activation has also been suggested to increase transcription of MAFbx and MuRF-1, and thereby the activation of ubiquitin-proteasome mediated muscle proteolysis, this raises the possibility that muscle fuel selection and the induction of a muscle atrophy programme could be regulated by a single common signalling pathway. We therefore investigated the effect of PPARdelta (delta) agonist, GW610742, administration on muscle mitochondrial function, fuel regulation, and atrophy and growth related signalling pathways in vivo. Twenty-four male Wistar rats received vehicle or GW610742 (5 and 100 mg per kg body mass (bm)) orally for 6 days. Soleus muscle was used to determine maximal rates of ATP production (MRATP) in isolated mitochondria, gene and protein expression, and enzyme activities. MRATP were unchanged by GW610742. Muscle PDK2 and PDK4 mRNA expression increased with GW610742 (100 mg (kg bm)(-1)) compared to vehicle (P<0.05), and was paralleled by a twofold increase in PDK4 protein expression (P<0.05). The activity of beta-hydroxyacyl-CoA dehydrogenase increased with GW610742 (P<0.05). Muscle MuRF1 and MAFbx mRNA expression was increased by GW610742 (100 mg (kg bm)(-1)) compared to vehicle (P<0.05), and was matched by increased protein expression (P<0.001), whilst Akt1 protein declined (P<0.05). There was no effect of GW610742 on 20S proteasome activity and mRNA expression, or the muscle DNA: protein ratio. GW610742 switched muscle fuel metabolism towards decreased carbohydrate use and enhanced lipid utilization, but did not induce mitochondrial dysfunction. Furthermore, GW610742 initiated a muscle atrophy programme, possibly via changes in the Akt1/FOXO/MAFbx and MuRF1 signalling pathway.


now i ampursuing, direct ways to increasing AMPK activity (but only at adipocytes).
AT least PPARs Alpha and Delta, raises suspicions in me.

what do you think ?, in the same dish; Myostain, Follistatin, Activin, PPARs, Beta2 Adrenergic agonists, PDK4.






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Muscle Nerve. 2005 Jan;31(1):34-40.

Loss of myostatin expression alters fiber-type distribution and expression of myosin heavy chain isoforms in slow- and fast-type skeletal muscle.

Girgenrath S, Song K, Whittemore LA.

Wyeth Department of Cardiovascular and Metabolic Diseases, 87 Cambridge Park Drive, Cambridge, Massachusetts 02140, USA.

Myostatin (Mstn) is a member of the transforming growth factor-beta family that negatively regulates skeletal muscle mass. Mstn knockout mice have greater skeletal muscle mass than wild-type littermates. We investigated the effect of Mstn on fiber type by comparing adult muscles from the murine Mstn knockout with wild-type controls. Based on myofibrillar ATPase staining, the soleus of Mstn knockout mice displays a larger proportion of fast type II fibers and a reduced proportion of slow type I fibers compared with wild-type animals. Based on staining for succinate dehydrogenase (SDH) activity, a larger proportion of glycolytic fibers and a reduced proportion of oxidative fibers occur in the extensor digitorum longus (EDL) of Mstn knockouts. These differences in distribution of fiber types are accompanied by differences in the expression of myosin heavy chain (MHC) isoforms. In both Mstn knockout soleus and EDL, larger numbers of faster MHC isoforms are expressed at the expense of slower isoforms when compared with wild-type littermates. Thus, the absence of Mstn in the knockout mouse leads to an overall faster and more glycolytic muscle phenotype. This muscle phenotype is likely a consequence of developmental processes, and inhibition of Mstn in adults does not cause a transformation to a more fast and glycolytic phenotype. Our findings suggest that myostatin has a critical role in regulating the formation, proliferation, or differentiation of fetal myoblasts and postnatal fibers.

.

Very nice post. Kudos!

OK, myostatin inhibitors are out.

follistatin agonism is out.

oswaldo - how difficult would it be to stimulate MKK4? I want to look into this more. Also, I want to look into HSL.

Dash - in response to your HDCI's suggestion:

this from the wiki:

Functions
Deacetylation removes acetyl groups from histone tails, causing the DNA to wrap more tightly around the histones and interfering with the transcription of genes by blocking access by transcription factors. The overall result of histone deacetylation is a global (non specific) reduction in gene expression.

seems like a harsh thing to undergo for some myostatin down reg. What else is being down regulated? Worth a pub peek.


Oh shit, Oswaldo - take a look at this from 2004-

Iezzi S, Di Padova M, Serra C, Caretti G, Simone C, Maklan E, Minetti G, Zhao P, Hoffman EP, Puri PL, Sartorelli V.
Muscle Gene Expression Group, Laboratory of Muscle Biology, NIAMS, National Institutes of Health, Bethesda, MD 20892, USA.

Fusion of undifferentiated myoblasts into multinucleated myotubes is a prerequisite for developmental myogenesis and postnatal muscle growth. We report that deacetylase inhibitors favor the recruitment and fusion of myoblasts into preformed myotubes. Muscle-restricted expression of follistatin is induced by deacetylase inhibitors and mediates myoblast recruitment and fusion into myotubes through a pathway distinct from those utilized by either IGF-1 or IL-4. Blockade of follistatin expression by RNAi-mediated knockdown, functional inactivation with either neutralizing antibodies or the antagonist protein myostatin, render myoblasts refractory to HDAC inhibitors. Muscles from animals treated with the HDAC inhibitor trichostatin A display increased production of follistatin and enhanced expression of markers of regeneration following muscle injury. These data identify follistatin as a central mediator of the fusigenic effects exerted by deacetylase inhibitors on skeletal muscles and establish a rationale for their use to manipulate skeletal myogenesis and promote muscle regeneration.

PMID: 15130492 [PubMed - indexed for MEDLINE]


now we have contradicting data on follistatin's usefullness as a myostatin down reulator AND we have a method - HDACi's.

More specifically : trichostatin A (TSA), and butyrate, and benzamide

TSA also has lipolytic effects:

Regulation of uncoupling protein-2 mRNA in L6 myotubules: II: Thyroid hormone amplifies stimulation of uncoupling protein-2 gene by thiazolidinediones and other peroxisome proliferator-activated receptor ligands in L6 myotubules: evidence for a priming effect.López-Solache I, Marie V, Camirand A, Silva JE.
Department of Medicine, Division of Endocrinology, Jewish General Hospital, Lady Davis Institute, McGill University, Montreal, Quebec, Canada.

The stimulation of the uncoupling protein-2 gene (ucp2) by thyroid hormone (triiodothyronine [T3]) in vivo is variable, suggesting complex interactions and even the possibility of indirect effects. We investigated the effect of T3 on ucp2 expression in L6 myotubules. Alone, T3 did not significantly stimulate ucp2 expression in L6 cells, but it amplified the stimulation by thiazolidinediones (TZDs). L6 cells expressed both alpha1 and beta1 thyroid hormone receptors and the data were consistent with the effect being mediated by these receptors. T3 also enhanced the stimulation of ucp2 by the nonselective peroxisome proliferator-activated receptor (PPAR) ligands bezafibrate and carbacyclin, but not that by oleic acid or norepinephrine. L6 cells expressed PPARbeta and PPARgamma, but not PPARalpha. As short as a 1-h preexposure of L6 cells to T3 was sufficient to amplify the effect of PPAR ligands. Neither transcription nor translation was needed for this effect of T3. T3 did not affect the t1/2 of UCP2 mRNA. The histone deacetylases inhibitor trichostatin A (TSA) stimulated the expression of ucp2 but did not add to the effect of T3 nor did this hormone enhance the effect of TSA. These results suggest that T3 selectively enhances the transcriptional stimulation of ucp2 by TZDs and nonselective PPAR ligands by priming the gene to a transactivating signal(s) generated by such ligands.

PMID: 12588052 [PubMed - indexed for MEDLINE]


look at the references to TZD's being synergistic to PPAR beta and gamma. Two things I had at first glance considered widely suggested against. Spook even warns against NOT taking TZDs..... but it looks like taken with Bezafibrate we may have a very good combo...


DASHFORCE DAMN YOU, YOU'VE DONE IT AGAIN!

Stage-specific modulation of skeletal myogenesis by inhibitors of nuclear deacetylases.Iezzi S, Cossu G, Nervi C, Sartorelli V, Puri PL.
Laboratory of Muscle Biology, Muscle Gene Expression Group, National Institute of Arthritis and Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD 20892, USA.

Nuclear acetyltransferases promote and deacetylases inhibit skeletal muscle-gene expression, suggesting the potential effectiveness of deacetylase inhibitors (DIs) in modulating skeletal myogenesis. Surprisingly, previous studies have indicated that DIs suppress myogenesis. The recent observations that histone deacetylases associate with the muscle-regulatory proteins MyoD and MEF2C only in undifferentiated myoblasts prompted us to evaluate the effect of DIs at distinct stages of the myogenic program. We found that exposure of established rodent and human muscle cells to distinct DIs has stage-specific effects. Exposure of undifferentiated skeletal myoblasts to DIs, followed by incubation in differentiation medium, enhanced the expression of muscle-specific reporters and increased the levels of endogenous muscle proteins, leading to a dramatic increase in the formation of multinucleated myotubes. By contrast, simultaneous exposure of muscle cells to differentiation medium and DIs inhibited the myogenic program. Likewise, embryos exposed in utero to nonteratogenic doses of DI at the early stages of somitic myogenesis (embryonic day 8.5) exhibited an increased number of somites and augmented expression of a muscle-specific transgene as well as endogenous muscle genes. The functional effects induced by DIs were mirrored by changes in the state of acetylation of histones present at a muscle-gene enhancer and of MyoD itself. These results represent the first evidence that DIs can enhance muscle differentiation and suggest the rationale for their use in manipulating adult and embryonic skeletal myogenesis.

PMID: 12032356 [PubMed - indexed for MEDLINE]

FDA approved HCDi - Zolinza. Bitches. Plan and simple the shit kills ALL cancer you'd ever get.

A few threads of interest... I've looked through them before...

http://www.mindandmuscle.net/forum/index.php?showtopic=11476
http://www.mindandmuscle.net/forum/index.php?showtopic=10495

Now why is myostatin inhibition out? Looks like this myostatin propeptide deserves some attention.

price tags

nice read... I have to say I'm a little proud that admittedly I've never seen either thread and I'm having the same ideas spook and nandi had....

at any rate they looked like they were both in favor of some kind of HCADi for our purposes just didn't have a safe one at the time.

.




i was going to ask about the same








laughs...............

very funny.



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Oswaldo -- what is your native tongue?

spanish.

venezuela.

if you two have that kind of cash to spend on this shit, you go right ahead. I'd love to read the log. However, I don't see it as very likely that doing research on something that is out of the realm of reasonably priced does anyone any good. At least on here.

for sure.

anyway for me, is very important, cos, myostatin is regulated by glucocorticoids, and myostatin is required for the catabolic effects of glucocorticoids (I suffer of hypercortisolemia).



.

i guess I don't understand why would should prattle on about a drug none of can afford. Unless of coarse you can somehow get script for it (maybe in Venezula this is possible?) and if so.... You need my home address

but if not, i think exploring alternate routes (maybe with affordable substances) would be extremely exciting.

Ah, chévere. Pasé buen rato en Puerto Rico y unos meses en Perú. Este verano voy a pasar un mes en Costa Rica -- stoy bien animado. De hecho anoche terminé un ensayo de 5 páginas (en español) sobre la dieta vegetariana... con lo difícil que me fue encontrar los vocablos adecuados para este tema, no me imagino cómo demonios tú te comunicas tan bien con nosotros, especialmente considerando el nivel de especialización de términos... Kudos.



I think you might be misunderstanding. I'm certainly not looking to purchase an MI and use it directly. I'm looking for means by which to manipulate it indirectly. Long-term things like HDACI, increasing androgen levels, cortisol modulation, dietary adjustments that might not make a WHAM-BAM, YOUVE GOT MUSCLES effect, but over the long term will be safe and effective routes to maximizing muscle gain and getting the most out of my genetic limit.

As a matter of fact, if I had the cash for an MI, I'd probably just go for lots of steroids and awesome PCT and liver protection.

Stuff like this.

1: Physiol Genomics. 2007 Mar 6;
Electroacupuncture Suppresses Myostatin Gene Expression: Cell Proliferative Reaction in Mouse Skeletal Muscle.
Takaoka Y, Ohta M, Ito A, Takamatsu K, Sugano A, Funakoshi K, Takaoka N, Sato N, Yokozaki H, Arizono N, Goto S, Maeda E.

Complementary and alternative medicine (CAM) may provide patients with an alternative to traditional medicine, but an assessment of its efficacy is required. One CAM method, electroacupuncture (EA) treatment, is a maneuver that utilizes stimulation of acupuncture needles with a low-frequency microcurrent. To study the effect of short-term EA, we evaluated the differential expression of genes induced by EA in mouse skeletal muscle for up to 24 hours. We then used RT-PCR to confirm the expression patterns of six differentially expressed genes. Bioinformatics analysis of their transcription control regions showed that EA-inducible genes have numerous common binding motifs that are related to cell differentiation, cell proliferation, muscle repair, and hyperplasia. These results suggested that EA treatment may induce cell proliferation in skeletal muscle. To verify this possibility, we used EA to stimulate mouse skeletal muscle daily for up to 1 month and examined the long-term effects. Immunohistochemical analysis showed that nuclei of muscle cells treated with EA for 1 month, especially nuclei of satellite cells, reacted with anti-human PCNA. Also, expression of the gene encoding myostatin, which is a growth repressor in muscle satellite cells, was suppressed by daily EA treatment for 1 week; EA treatment for 1 month resulted in more marked suppression of the gene. These molecular findings constitute strong evidence that EA treatment suppresses myostatin expression, which leads to a satellite cell related proliferative reaction and repair in skeletal muscle. Key words: acupuncture, electrical current, satellite cell, muscle repair, regeneration.

PMID: 17341691 [PubMed - as supplied by publisher]

ditto, hence my follistatin obsession. There has to be a way to make norphenephrene more bioavailable. What about a nasal spray?

Also available as a rectal suppository.

You seem convinced that this is better than good old ephedrine or clen. Why?

eyy que buen español ! astonishing ! me impresiona.
puedo leer cualquier cosa en ingles, pero su gramatica es otra cosa.


.

the problem with HDAC inhibitors, is the fact is that they are of specific stage , if you apply in the wrong phase, they can be anti growth.

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