I've only seen this mentioned off handedly or in relations to the Angiotensin II issues, but not addressed in and of itself.

Natriuretic peptides: a new lipolytic pathway in human adipocytes.Sengenès C, Berlan M, De Glisezinski I, Lafontan M, Galitzky J.
INSERM U 317 and Laboratoire de Pharmacologie Médicale et Clinique, Faculté de Médecine, Toulouse Cedex, France.

Atrial natriuretic peptide (ANP) receptors have been described on rodent adipocytes and expression of their mRNA is found in human adipose tissue. However, no biological effects associated with the stimulation of these receptors have been reported in this tissue. A putative lipolytic effect of natriuretic peptides was investigated in human adipose tissue. On isolated fat cells, ANP and brain natriuretic peptide (BNP) stimulated lipolysis as much as isoproterenol, a nonselective beta-adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. In situ microdialysis experiments confirmed the potent lipolytic effect of ANP in abdominal s.c. adipose tissue of healthy subjects. A high level of ANP binding sites was identified in human adipocytes. The potency order defined in lipolysis (ANP > BNP > CNP) and the ANP-induced cGMP production sustained the presence of type A natriuretic peptide receptor in human fat cells. Activation or inhibition of cGMP-inhibited phosphodiesterase (PDE-3B) (using insulin and OPC 3911, respectively) did not modify ANP-induced lipolysis whereas the isoproterenol effect was decreased or increased. Moreover, inhibition of adenylyl cyclase activity (using a mixture of alpha(2)-adrenergic and adenosine A1 agonists receptors) did not change ANP- but suppressed isoproterenol-induced lipolysis. The noninvolvement of the PDE-3B was finally confirmed by measuring its activity under ANP stimulation. Thus, we demonstrate that natriuretic peptides are a new pathway controlling human adipose tissue lipolysis operating via a cGMP-dependent pathway that does not involve PDE-3B inhibition and cAMP production.

PMID: 10877827 [PubMed - indexed for MEDLINE]


I looks to me like a whole new pathway that isn't being utilized...


Wiki has a couple of interesting things to say about the subject:





This causes me to wonder what fluid retention or lack thereof would be if we manipulated both angiotensin and ANP dually...



this also makes me wonder if this system will go virtually unutilized even at a normal physological perspective if a ARB is being used...

Colin - if you are still in the habit of caring about not killing yourself this could be a nice little tid bit for you:



Right now it looks as though we have to wait on a modulator unless we can discovery one naturally...





http://en.wikipedia.org/wiki/Atrial_natriuretic_peptide

research continues... Still working on getting up to date

: Nutr Metab Cardiovasc Dis. 2003 Aug;13(4):244-9.Links
Role of the natriuretic peptide system in lipogenesis/lipolysis.Dessì-Fulgheri P, Sarzani R, Rappelli A.
Clinica di Medicina Interna, Azienda Ospedaliera Umberto I, Via Conca, 60020 Ancona, Italy. dessi@unian.it

AIM: There is recent evidence that the natriuretic peptide (NP) system promotes adipose tissue lipolysis in primates. This effect is mediated by the interaction of NP with its active receptors through guanylyl cyclase activation and cGMP production. This review will briefly focus on the new aspects of NP pathophysiology in man. DATA SYNTHESIS: NP receptors have been described in rodent adipocytes, and the expression of their mRNA is found in human adipose tissue together with high level of ANP binding sites. In isolated fat cells, atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) were able to stimulate lipolysis as much as isoproterenol, a non-selective beta-adrenergic receptor agonist, whereas C-type natriuretic peptide (CNP) had the lowest lipolytic effect. The potent lipolytic effect of NP has also been confirmed in samples of abdominal adipose tissue from healthy subjects. The potency order of the lipolytic effect (ANP > BNP > CNP) and ANP-induced cGMP production supported the presence of type A natriuretic peptide receptor in human fat cells. The effect of NP on lipid metabolism is confirmed by the fact that intravenous ANP infusion is followed by plasma NEFA and glycerol concentration increase (reflecting lipid mobilisation). CONCLUSIONS: The NP system seems to play an important role in lipid metabolism, possibly affecting the pathophysiology of obesity and obesity-related disorders, such hypertension. Further studies, however, are needed to completely establish the mechanisms involved in NP-induced lipolysis and the real relevance of this new pathway specific of primates.
PMID: 14650358 [PubMed - indexed for MEDLINE]

: Int J Obes Relat Metab Disord. 2002 Jan;26(1):24-32. Links
Increased lipolysis in adipose tissue and lipid mobilization to natriuretic peptides during low-calorie diet in obese women.Sengenes C, Stich V, Berlan M, Hejnova J, Lafontan M, Pariskova Z, Galitzky J.
INSERM Unité 317, Laboratory of Medical and Clinical Pharmacology, Faculty of Medicine, Toulouse, France.

OBJECTIVE: We recently demonstrated that natriuretic peptides (NP) are involved in a pathway inducing lipolysis in human adipose tissue. Atrial NP (ANP) and brain NP (BNP) operate via a cGMP-dependent pathway which does not involve phosphodiesterase-3B inhibition or cAMP. The study was performed to evaluate the effect of ANP on lipid mobilization in obese women and secondly to examine the possible effect of a low-calorie diet (LCD) on the lipolytic response of subcutaneous abdominal fat cells to NP and on the lipid mobilization induced by ANP infusion (1 microg/m(2) min for 60 min). SUBJECTS: Ten obese women from 40.5+/-3.4 y old were selected for this study. Their body weight was 96.4+/-5.7 kg and their BMI was 35.3+/-1.7 kg/m(2). They received a 2.5-2.9 MJ/day formula diet for 28 days. DESIGN: Before and during the LCD, an adipose tissue biospy was performed for in vitro studies and, moreover, ANP was perfused i.v. to evaluate its lipid mobilizing action in toto and in situ in subcutaneous abdominal adipose tissue (SCAAT) using microdialysis. RESULTS: The lipolytic effects of isoproterenol, ANP, BNP and bromo-cGMP (an analogue of cGMP) on fat cells increased by about 80-100% during LCD. The lipid mobilization during i.v. ANP infusion, assessed by plasma non-esterified fatty acids (NEFA) increase was enhanced during the LCD. However, during LCD, ANP infusion induced a biphasic effect on glycerol concentration in plasma and interstitial fluid of SCAAT; a significant increase was observed in glycerol levels during the first 30 min infusion period, followed by a steady decrease. The concentration of glycerol was lower during the post-infusion period than during the baseline period. This effect was stronger in obese subjects submitted to the LCD with a low-carbohydrate composition. Other plasma parameters were weakly increased (noradrenaline) or not modified (insulin, glucose) by ANP infusion and no difference was found before and during LCD treatment. CONCLUSION: The present study shows that NP are powerful lipolytic agents in subcutaneous fat cells and that both isoproterenol- and NP-induced lipolysis increase during LCD, in obese women. These changes seem to be associated with an improvement of the lipolytic pathway at a post-receptor level. Moreover, i.v. administration of ANP induced a lipid mobilizing effect which was enhanced by a LCD in these objects.

PMID: 11791143 [PubMed - indexed for MEDLINE]

Low calorie diet raised 100% on it's own in obese women... This is the second study that showed good results in abdominal subQ adipocytes.

: Med Sci (Paris). 2005 Dec;21 Spec No:29-33.Links
[Natriuretic peptides: a new lipolytic pathway in human fat cells][Article in French]


Sengenes C, Moro C, Galitzky J, Berlan M, Lafontan M.
Unité de recherches sur les obésités, Inserm U.586, Institut Louis Bugnard, CHU de Toulouse, TSA50032, 31059 Toulouse Cedex 9, France.

Human fat cell lipolysis was considered until recently to be an exclusive cAMP/protein-kinase A (PKA)-regulated metabolic pathway under the control of catecholamines and insulin. Moreover, exercise-induced lipid mobilization in humans was considered to mainly depend on catecholamine action and interplay between fat cell beta- and alpha2-adrenergic receptors controlling adenylyl cyclase activity and cAMP production. We have recently demonstrated that natriuretic peptides stimulate lipolysis and contribute to the regulation of lipid mobilization in humans. Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) stimulate lipolysis in human isolated fat cells. Activation of the adipocyte plasma membrane type A guanylyl cyclase receptor (NPR-A), increase in intracellular guanosine 3',5'-cyclic monophosphate (cyclic GMP) levels and activation of hormone-sensitive lipase mediate the action of ANP. ANP does not modulate cAMP production and PKA activity. Increment of cGMP induces the phosphorylation of hormone-sensitive lipase and perilipin A via the activation of a cGMP dependent protein kinase-I (cGK-I). Plasma concentrations of glycerol and nonesterified fatty acids are increased by i.v. infusion of ANP in humans. Physiological relevance of the ANP-dependent pathway was demonstrated in young subjects performing physical exercise. ANP plays a role in conjunction with catecholamines in the control of exercise-induced lipid mobilization. This pathway becomes of major importance when subjects are submitted to chronic treatment with a beta-blocker. Oral beta-adrenoceptor blockade suppresses the beta-adrenergic component of catecholamine action in fat cells and potentiates exercise-induced ANP release by the heart. These findings may have several implications whenever natriuretic peptide secretion is altered such as in subjects with left ventricular dysfunction, congestive heart failure and obesity.

PMID: 16598902 [PubMed - indexed for MEDLINE]

this study just paraphrases what we already know, but in young subjects which suggests it's safe. It's independant of cAMP and doesn't modulate cGMP it also isn't modulated by catecholamine production.... So far we only see injecting ANP to be an effective modulator... In the text above it mentions some modulation going on, but it was slightly over my head so I could be missing something.

: Am J Physiol Regul Integr Comp Physiol. 2007 Aug;293(2):R612-7. Epub 2007 Jun 6. Links
Atrial natriuretic peptide contribution to lipid mobilization and utilization during head-down bed rest in humans.Moro C, Pillard F, de Glisezinski I, Crampes F, Thalamas C, Harant I, Marques MA, Lafontan M, Berlan M.
Institut National de la Santé et de la Recherche Médicale, U858, Laboratoire de Recherche sur les Obésités, Toulouse, France.

Head-down bed rest (HDBR) increases plasma levels of atrial natriuretic peptide (ANP) and decreases norepinephrine levels. We previously demonstrated that ANP promotes lipid mobilization and utilization, an effect independent of sympathetic nervous system activation, when infused into lean healthy men at pharmacological doses. The purpose of the present study was to demonstrate that a physiological increase in ANP contributes to lipid mobilization and oxidation in healthy young men. Eight men were positioned for 4 h in a sitting (control) or in a HDBR position. Indexes of lipid mobilization and hormonal changes were measured in plasma. Extracellular glycerol, an index of lipolysis, was determined in subcutaneous adipose tissue (SCAT) with a microdialysis technique. A twofold increase in plasma ANP concentration was observed after 60 min of HDBR, and a plateau was maintained thereafter. Plasma norepinephrine decreased by 30-40% during HDBR, while plasma insulin and glucose levels did not change. The level of plasma nonesterified fatty acids was higher during HDBR. SCAT lipolysis, as reflected by interstitial glycerol, as well as interstitial cGMP, the second messenger of the ANP pathway, increased during HDBR. This was associated with an increase in blood flow observed throughout HDBR. Significant changes in respiratory exchange ratio and percent use of lipid and carbohydrate were seen only after 3 h of HDBR. Thus the proportion of lipid oxidized increased by 40% after 3 h of HDBR. The rise in plasma ANP during HDBR was associated with increased lipolysis in SCAT and whole body lipid oxidation. In this physiological setting, independent of increasing catecholamines, our study suggests that ANP contributes to lipid mobilization and oxidation in healthy young men.
PMID: 17553844 [PubMed - indexed for MEDLINE]

LCD + watching Brave Heart laying flat on your back = 200% increase in ANP... Could this seriously get any easier? Holy shit... We need a natural ANP agonist immediately.

The double edge of this blade... Could utilizing this pathway shut down our leptin secreation?

Diabetologia. 2007 May;50(5):1038-47. Epub 2007 Feb 23. Links
Atrial natriuretic peptide inhibits the production of adipokines and cytokines linked to inflammation and insulin resistance in human subcutaneous adipose tissue.Moro C, Klimcakova E, Lolmède K, Berlan M, Lafontan M, Stich V, Bouloumié A, Galitzky J, Arner P, Langin D.
INSERM, U586, Obesity Research Unit, Toulouse, France.

AIMS/HYPOTHESIS: Increased adipose tissue secretion of adipokines and cytokines has been implicated in the chronic low-grade inflammation state and insulin resistance associated with obesity. We tested here whether the cardiovascular and metabolic hormone atrial natriuretic peptide (ANP) was able to modulate adipose tissue secretion of several adipokines (derived from adipocytes) and cytokines (derived from adipose tissue macrophages). SUBJECTS AND METHODS: We used protein array to measure the secretion of adipokines and cytokines after a 24-h culture of human subcutaneous adipose tissue pieces treated or not with a physiological concentration of ANP. The effect of ANP on protein secretion was also directly studied on isolated adipocytes and macrophages. Gene expression was measured by real-time RT-quantitative PCR. RESULTS: ANP decreased the secretion of the pro-inflammatory cytokines IL-6 and TNF-alpha, of several chemokines, and of the adipokines leptin and retinol-binding protein-4 (RBP-4). The secretion of the anti-inflammatory molecules IL-10 and adiponectin remained unaffected. The cytokines were mainly expressed in macrophages that expressed all components of the ANP-dependent signalling pathway. The adipokines, leptin, adiponectin and RBP-4 were specifically expressed in mature adipocytes. ANP directly inhibited the secretion of IL-6 and monocyte chemoattractant protein-1 by macrophages. The inhibitory effects of ANP on leptin and growth-related oncogene-alpha secretions were not seen under selective hormone-sensitive lipase inhibition. CONCLUSIONS/INTERPRETATION: We suggest that ANP, either by direct action on adipocytes and macrophages or through activation of adipocyte hormone-sensitive lipase, inhibits the secretion of factors involved in inflammation and insulin resistance.

PMID: 17318625 [PubMed - indexed for MEDLINE]


couple factors come to mind - A. this changes nothing about leptin's expression. B. Right now we're just talking about temporarily enducing ANP increases... so it would only be effecting these things negatively in short periods.

Note on titty fat - IL-6 inhibition is good - see a study I posted in oswaldo's 'cell pool' thread.

work calls.... hopefully this generates some discussion. Come on Heavy - let's see what you got!

Found one:

Urinary responses to acute moxonidine are inhibited by natriuretic peptide receptor antagonist
Rouwayda El-Ayoubi,1 Ahmed Menaouar,1 Jolanta Gutkowska,1 and Suhayla Mukaddam-Daher1*
1Laboratory of Cardiovascular Biochemistry, Centre hospitalier de l'Université de Montréal-Hotel-Dieu, and Department of Medicine, Université de Montréal, Montreal (Quebec), Canada
*Author for correspondence: Email: suhayla.mukaddam-daher@umontreal.ca
Received September 13, 2004; Revised November 26, 2004; Accepted December 9, 2004.




looks extremely safe sirs -

wiki: http://en.wikipedia.org/wiki/Moxonidine

that's what I'm talking about.

Always noticed waist looked smaller after a few hours of HDBR.

Very interesting topic. I'll bring a full text or two to track meet this evening.

HDBR seems easier than exercise, although one need not exercise too strenuously. Nearly 3x increase at 55% VO2 MAX, at least as effective as 75% VO2 MAX.

"An exercise lasting 90 min at a work level averaging 55% VO2 MAX when heart rate was kept almost
constant (124 bpm), led also to a significant and rapid increase in plasma ANP. ANP did
not reach a constant level (Fig. 3), but an ascending trend was observed till the end of the exercise
despite a constant heart rate."

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

Increase in atrial natriuretic peptide in response to physical exercise

Summary. Circulating atrial natriuretic peptide (ANP) level was determined during physical exercise
to investigate the correlation between changes in ANP level and heart rate increases. Six subjects exercised at a work level of 75% VO2 max for 30 min, two also performed two successive exercises at 75% VO2 MAX while two more exercised
for longer at 55% VO2 MAX 9 Plasma ANP levels and heart rate increased in all the exercising subjects. At the end of the exercise, the ANP level fell immediately, suggesting an immediate reduction in ANP secretion by the heart. Pre-exercise
values were reached after 30 min. Successive exercises gave the same heart rate related ANP patterns without previous secretory episodes having any effect. These results lead to the conclusion that ANP intervenes in the cardiovascular adjustments
to exercise.

ruminations on renin, angiotensin, aldosterone, cortisol and anp.


Obesity (Silver Spring). 2007 Sep;15(9):2200-8.

High dietary sodium intake increases white adipose tissue mass and plasma leptin in rats.

Fonseca-Alaniz MH, Brito LC, Borges-Silva CN, Takada J, Andreotti S, Lima FB.

Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of Sao Paulo, 1524 Prof Lineu Prestes Ave., 05508-900, Sao Paulo, SP, Brazil.

OBJECTIVE: Salt restriction has been reported to increase white adipose tissue (WAT) mass in rodents. The objective of this study was to investigate the effect of different sodium content diets on the lipogenic and lipolytic activities of WAT. RESEARCH METHODS AND PROCEDURES: Male Wistar rats were fed on normal-sodium (NS; 0.5% Na(+)), high-sodium (HS; 3.12% Na(+)), or low-sodium (LS; 0.06% Na(+)) diets for 3, 6, and 9 weeks after weaning. Blood pressure (BP) was measured using a computerized tail-cuff system. At the end of each period, rats were killed and blood samples were collected for leptin determinations. The WAT from abdominal and inguinal subcutaneous (SC), periepididymal (PE) and retroperitoneal (RP) depots was weighed and processed for adipocyte isolation, rate measurement of lipolysis and d-[U-(14)C]-glucose incorporation into lipids, glucose-6-phosphate dehydrogenase (G6PDH) and malic enzyme activity evaluation, and determination of G6PDH and leptin mRNA expression. RESULTS: After 6 weeks, HS diet significantly increased BP; SC, PE, and RP WAT masses; PE adipocyte size; plasma leptin concentration; G6PDH activity in SC WAT; and PE depots and malic activity only in SC WAT. The leptin levels correlated positively with WAT masses and adipocyte size. An increase in the basal and isoproterenol-stimulated lipolysis and in the ability to incorporate glucose into lipids was observed in isolated adipocytes from HS rats. DISCUSSION: HS diet induced higher adiposity characterized by high plasma leptin concentration and adipocyte hypertrophy, probably due to an increased lipogenic capacity of WAT.




.

Will Moxonidine give us the same effects?

J Int Med Res. 2008 Jan-Feb;36(1):80-7.Links
Effects of sympatholytic therapy with moxonidine on serum adiponectin levels in hypertensive women.Ebinç H, Ozkurt ZN, Ebinç FA, Ucardag D, Caglayan O, Yilmaz M.
Department of Cardiology, School of Medicine, University of Kirikkale, Kirikkale, Turkey.

We examined whether moxonidine influences lipid profile, insulin resistance, adiponectin levels, renal function and microalbuminuria in women with essential hypertension in a study of 55 non-diabetic hypertensive patients and 53 normotensive women. Hypertensive patients received moxonidine for 12 weeks. At baseline the hypertensive group had significantly higher mean blood pressure, low-density lipoprotein cholesterol, triglycerides, total cholesterol, fasting glucose, urinary albumin excretion and homeostasis model assessment of insulin resistance (HOMA-IR), together with significantly lower mean high-density lipoprotein cholesterol, creatinine clearance and serum adiponectin than the normotensive group. Moxonidine significantly decreased blood pressure, fasting glucose, triglycerides, total cholesterol, HOMA-IR and albumin excretion, but significantly increased serum adiponectin. The change in adiponectin level was negatively correlated with the change in HOMA-IR. Moxonidine treatment may improve unfavourable metabolic status related to insulin resistance by increasing adiponectin levels in patients with essential hypertension. Since it can improve adiponectin levels, it may be used in the antihypertensive treatment of patients at high risk of diabetes and cardiovascular disease.
PMID: 18230271 [PubMed - in process]


Ok cool... How do we know it's because of ANP? First, because I said so and next because:


Eur J Pharmacol. 2006 Jul 10;541(1-2):73-9. Epub 2006 May 12. Links
Receptors involved in moxonidine-stimulated atrial natriuretic peptide release from isolated normotensive rat hearts.Mukaddam-Daher S, Menaouar A, Gutkowska J.
Centre Hospitalier de L'Université de Montréal Research Center, Campus Hotel-Dieu, Montréal, Quebec, Canada.

Imidazoline I1-receptors are present in the heart and may be involved in atrial natriuretic peptide (ANP) release. The following studies investigated whether moxonidine (an antihypertensive imidazoline I1-receptor and alpha2-adrenoceptor agonist) acts directly on the heart to stimulate ANP release, and to characterize the receptor type involved in this action. Perfusion of rat (200-225 g) isolated hearts with moxonidine (10(-6) and 10(-5) M), for 30 min, resulted in ANP release (83+/-29 and 277+/-70 ng/30 min, above basal, respectively), significantly (P<0.01) different from perfusion with buffer (-6+/-31 ng/30 min). ANP release stimulated by moxonidine (10(-6) M) was inhibited by co-perfusion with the antagonists, AGN192403 (imidazoline I1-receptor), phenoxybenzamine (alpha2>alpha1-adrenoceptors), and prazosin (alpha1>alpha2-adrenoceptors), but increased by rauwolscine (alpha2-adrenoceptors). Perfusion with 10(-5) M brimonidine (full alpha2-adrenoceptor agonist) inhibited moxonidine-stimulated ANP release. Similarly, moxonidine (10(-6) M) tended to reduce coronary flow, but significantly increased coronary flow in the presence of brimonidine, which was vasoconstrictive when perfused alone. Coronary flow was reduced by 10(-5) M each, brimonidine>clonidine>moxonidine; while similar bradycardia was observed with clonidine and moxonidine, but not with brimonidine. In conclusion, these results argue in favor of moxonidine acting primarily on imidazoline I1-receptors to release ANP, with both alpha2-adrenoceptor and imidazoline I1-receptors exerting inhibitory inter-relation. In contrast, the coronary vasodilatory effect of moxonidine requires full activation of alpha2-adrenoceptor. The sympatholytic and ANP-releasing effects of moxonidine appear to be mediated by cardiac imidazoline receptors that may be differentially localized. Most importantly, moxonidine can stimulate ANP release from the heart without contribution of the central nervous system.

PMID: 16774751 [PubMed - indexed for MEDLINE]


yeah folks... We have winna of a chicken dinna

1. Interesting Jake, Moxonidine was FDA aproved in 2000, and given it's apparent beneficial properties

'significantly decreased blood pressure, fasting glucose, triglycerides, total cholesterol, HOMA-IR and albumin excretion, but significantly increased serum adiponectin"

I can't imagine why this stuff isn't being pushed like statins.

2. I wasn 't familiar with the head down bed rest info, but there are numerous inversions in yoga which are reported to have various benefits (Roger Cole is an authority on physiology yoga and talks about this) including decreasing catecholamines. So if head down bed rest is good, is being inverted better? Pg 6 IIIB the great restorer advanced version is a a powerful inversion, easily done by anyone, no training required (unlike head and shoulderstand):

http://www.mindandmuscle.net/articles/scot...on-2?page=0%2C5

All these lipolysis mechanisms are great... now when are we going to fix the oxidation stuff (which is the rate-limiting step here)?

http://www.freepatentsonline.com/6066643.html

Tonight I'm placing wooden blocks under one end of bed to create a 6% incline. Sweet ANP dreams.

On further consideration, HDBR is not very effective.

-ANP was significantly higher after 60 minutes of HDBR vs. sitting control. Norepinephrine, however, was significantly lower after 60 minutes.

-Markers of increased lipolysis (plasma NEFA and glycerol) were significantly elevated only at 30 - 90 minutes and 30 minutes, respectively. Moreover, the oxidation referred to in the abstract is a change in substrate utilization (towards lipids in HDBR), not an increased over-all energy expenditure.

-Resting energy expenditure progressively decreased in HDBR, while sitting RER remained constant. The difference did not reach the level of significance. (It might after 4 hours though).

So:

ANP elevation with SNS depression is good for changing substrate utilization, but not increasing total energy expenditure.

Is there some reason to elevate cGMP? cGMP was significantly elevated from 60 minutes onward. Now, cGMP elevation will increase the activity of HSL, but this was clearly already accounted for by measurement of substrate oxidation rates.

.



Arterioscler Thromb Vasc Biol. 2005 Oct;25(10):2032-42.

An unsuspected metabolic role for atrial natriuretic peptides: the control of lipolysis, lipid mobilization, and systemic nonesterified fatty acids levels in humans.

Lafontan M, Moro C, Sengenes C, Galitzky J, Crampes F, Berlan M.

IFR-31, Institut Louis Bugnard, Hôpital Rangueil, Institut National de la Santé et de la Recherche Médicale, Inserm U586, 31432 Toulouse cedex 4, France. Max.Lafontan@toulouse.inserm.fr

In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. NPs have recently been found to exert potent lipolytic effects (ie, activating the breakdown of stored triacylglycerols) in isolated human fat cells and to promote lipid mobilization in vivo. Atrial natriuretic peptide increases the intracellular 3', 5'-cyclic guanosine monophosphate (cGMP) concentration which activates cGMP-dependent protein kinase leading to perilipin and hormone-sensitive lipase phosphorylation and lipolysis. NPs promote lipid mobilization when administered intravenously. NPs are also responsible for the residual lipid-mobilizing action observed under oral beta-blockade in subjects performing physical exercise. NPs are therefore novel factors which may open promising research pathways to explain the control of lipid mobilization in physiological and pathological conditions. The metabolic impact of altered production and circulation of NPs remains to be established. The potential influence of NPs on the development of lipid disorders, obesity-related cardiovascular events, and cardiac cachexia will be discussed in this review.



FASEB J. 2004 May;18(7):908-10.

Atrial natriuretic peptide contributes to physiological control of lipid mobilization in humans.

Moro C, Crampes F, Sengenes C, De Glisezinski I, Galitzky J, Thalamas C, Lafontan M, Berlan M.

Unité de recherches sur les Obésités, Institut National de la Santé et de la Recherche Médicale U586 ,Toulouse, France.

In humans, lipid mobilization is considered to depend mainly on sympathetic nervous system activation and catecholamine action. A contribution of ANP was hypothesized because we have previously shown that atrial natriuretic peptide (ANP) is a lipolytic agent on isolated human fat cells. Control of lipid-mobilizing mechanisms was investigated using in situ microdialysis in subcutaneous adipose tissue (SCAT) in healthy young men during two successive exercise bouts performed at 35% and 60% peak oxygen consumption (VO2max) after placebo or acute oral tertatolol (nonselective beta-antagonist) treatment. In placebo-treated subjects, infusion of propranolol in the probe (100 micromol/l) only partially reduced (40%) the increment in extracellular glycerol concentration (EGC) promoted by exercise. Moreover, oral beta-adrenergic receptor blockade did not prevent exercise-induced lipid mobilization in SCAT while exerting fat cell beta-adrenergic receptor blockade. Exercise-induced increase in plasma ANP was potently amplified by oral tertatolol. A positive correlation was found between EGC and plasma ANP levels but also between extracellular cGMP (i.e., index of ANP-mediated lipolysis) and EGC. Thus, we demonstrate that exercise-induced lipid mobilization resistant to local propranolol and lipid-mobilizing action observed under oral beta-blockade is related to the action of ANP. Oral beta-adrenergic receptor blockade, which potentiates exercise-induced ANP release by the heart, may contribute to lipid mobilization in SCAT. The potential relevance of an ANP-related lipid-mobilizing pathway is discussed.



Am J Physiol Endocrinol Metab. 2006 May;290(5):E864-9.

Atrial natriuretic peptide stimulates lipid mobilization during repeated bouts of endurance exercise.

Moro C, Polak J, Hejnova J, Klimcakova E, Crampes F, Stich V, Lafontan M, Berlan M.

Franco-Czech Laboratory for Clinical Research on Obesity, French Institute of Health and Medical Research (INSERM U586), Toulouse,

Atrial natriuretic peptide (ANP) controls lipolysis in human adipocytes. Lipid mobilization is increased during repeated bouts of exercise, but the underlying mechanisms involved in this process have not yet been delineated. The relative involvement of catecholamine- and ANP-dependent pathways in the control of lipid mobilization during repeated bouts of exercise was thus investigated in subcutaneous adipose tissue (SCAT) by microdialysis. The study was performed in healthy males. Subjects performed two 45-min exercise bouts (E1 and E2) at 50% of their maximal oxygen uptake separated by a 60-min rest period. Extracellular glycerol concentration (EGC), reflecting SCAT lipolysis, was measured in a control probe perfused with Ringer solution and in two other probes perfused with either Ringer plus phentolamine (alpha(1/2)-AR antagonist) or Ringer plus both phentolamine and propranolol (beta-AR antagonist). Plasma epinephrine, plasma glycerol, and EGC were 1.7-, 1.6-, and 1.2-fold higher in E2 than in E1, respectively. Phentolamine potentiated exercise-induced EGC increase during E2 only. Propranolol reduced the lipolytic rate during both E1 and E2 compared with the probe with phentolamine. Plasma ANP concentration increased more during E2 than during E1 and was correlated with the increase in EGC in the probe containing phentolamine plus propranolol. The results suggest that ANP is involved in the control of lipolysis during exercise and that it contributes to stimulation of lipolysis during repeated bouts of exercise.



Pharmacol Res. 2006 Jun;53(6):482-91.

Adipose tissue lipolysis as a metabolic pathway to define pharmacological strategies against obesity and the metabolic syndrome.

Langin D.

Obesity Research Unit Inserm UPS U586, Institut Louis Bugnard, Université Paul Sabatier, CHU Rangueil, Toulouse, France.

Adipose tissue lipolysis is the catabolic process leading to the breakdown of triglycerides stored in fat cells and release of fatty acids and glycerol. Recent work has revealed that lipolysis is not a simple metabolic pathway stimulated by catecholamines and inhibited by insulin. There have been new discoveries on the endocrine and paracrine regulation of lipolysis and on the molecular mechanisms of triglyceride hydrolysis. Catecholamines modulate lipolysis through lipolytic beta-adrenoceptor and antilipolytic alpha2-adrenoceptor. Recent studies have allowed a better understanding of the relative contribution of the two types of receptors and provided evidence for the in vivo involvement of alpha2-adrenoceptors in the physiological control of subcutaneous adipose tissue lipolysis. A puzzling observation is the characterization of a residual catecholamine-induced lipolysis in mice deficient in beta-adrenoceptors. A novel lipolytic system has been characterized in human fat cells. Natriuretic peptides stimulate lipolysis through a cGMP-dependent pathway. There are other lipolytic pathways active in human fat cells which importance is not fully understood. Forty years after the description of the antilipolytic effect of nicotinic acid, the receptors have been identified. Adrenomedullin which is produced by adipocytes exert an antilipolytic effect through an indirect mechanism involving nitric oxide. The molecular details of the lipolytic reaction are not fully understood. The role of the lipases has been re-evaluated with the cloning of adipose triglyceride lipase. Hormone-sensitive lipase appears as the major lipase for catecholamine and natriuretic peptide-stimulated lipolysis whereas adipose triglyceride lipase mediates the hydrolysis of triglycerides during basal lipolysis. Translocation of hormone-sensitive lipase bound to the adipocyte lipid binding protein to the lipid droplet seems to be an important step during lipolytic activation. Re-organization of the lipid droplet coating by perilipins facilitates the access of the enzyme. The role of other lipid-interacting proteins in lipolysis is still unclear. The proteins involved in the lipolytic process constitute drug targets for the treatment of obesity and the metabolic syndrome. The oldest example is nicotinic acid (niacin) used as a hypolipidaemic drug. A first approach consists in molecules stimulating lipolysis and oxidation of the released fatty acids to decrease fat stores. A second approach is a chronic inhibition of lipolysis to diminish plasma fatty acid level which is a central feature of the metabolic syndrome.



Med Sci Sports Exerc. 2005 Jul;37(7):1126-32.

Training enhances ANP lipid-mobilizing action in adipose tissue of overweight men.

Moro C, Pillard F, De Glisezinski I, Harant I, Rivière D, Stich V, Lafontan M, Crampes F, Berlan M.

Franco-Czech Laboratory for Clinical Research on Obesity, Inserm U586, Institut Louis Bugnard, Centre Hospitalier Universitaire de Toulouse, Université Paul Sabatier, Toulouse, France.

PURPOSE: This study was designed to evaluate whether a 4-month endurance training program could improve ANP- as well as isoproterenol-mediated (beta-adrenergic receptor agonist) in situ lipolysis and adipose tissue blood flow (ATBF) in the subcutaneous adipose tissue (SCAT) of untrained overweight subjects. METHODS: Ten overweight men aged 26.0 +/- 1.4 yr with a mean body mass index of 27.6 +/- 0.2 kg.m(-2), performed aerobic exercise 5 d.wk(-1) for 4 months. Before and after the training period, SCAT responsiveness was investigated in situ during a 60-min infusion of 1 micromol.L(-1) isoproterenol and 10 micromol.L(-1) ANP through microdialysis probes. Plasma metabolic parameters and physical fitness variables were measured as well. RESULTS: Endurance training significantly increased fat-free mass and VO2max, while reducing plasma insulin, glucose, NEFA, low density lipoprotein (LDL)-C and the respiratory exchange ratio at rest. Training significantly lowered resting dialysate glycerol levels in SCAT. The lipid-mobilizing effect of ANP was markedly enhanced (by 191%, P < 0.05) after training as was that of isoproterenol (by 145%, P < 0.05). Resting adipose tissue blood flow as well as ANP- and isoproterenol-mediated rise in ATBF was increased after training. CONCLUSION: The present study shows that endurance training improves ANP- as well as beta-adrenergic-receptor-mediated lipid mobilization and ATBF in the SCAT of overweight subjects. The recovery of a higher lipolytic efficiency in adipose tissue is an important benefit of a training program in overweight subjects.








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OK, I think the lipolytic effects of ANP have been established . Suggest further research be direceted toward ANP agonists, imidazoline I1-receptors, etc.

Some more thoughts on HDBR:

While REE is lower during HDBR vs. sitting, it may be elevated vs. a conventional sleep position. Assume conventional sleep positions do not elevate ANP, or the experimentors would have saved themselves the trouble of elevating one end of the bed. If the SNS downregulates during in a conventional sleep position as it does with HDBR, HDBR should create a higher REE.
(ANP - SNS downreg > SNS downreg)

HDBR may promote a more restorative sleep (see ScottL's yoga article).

At worst, REE with HDBR will be no lower than REE during conventional sleep. Might as well reap the benefits of ANP modulation on IL-6, etc.

Dash - why wouldn't a caloric deficit qualify as a good method upregulating oxidation? Real question. Not being shitty. Especially a nap pre workout... But who has the time? Thus, the moxo

couldn't agree more. See post 11 to catch up with the big man.

Thanks, I saw it. My post was a way of saying 'enough with the lipolysis absracts' without being nasty.

This post was in regard to HDBR overnight for body-comp improvement, where it will not be very effective (except for perhaps more restorative sleep) unless REE is higher vs conventional sleep.

Short nap and a stim is a different story

Isn't cGMP an intermediate messenger in the hormone receptor -> adenyl cyclase signaling cascade? Receptor, cGMP -> adenyl cyclase -> cAMP?



Sure, caloric deficit would do nicely. But even in deficit, oxidation is still rate-limiting and not lipolysis (AFAIK). Thus, further improving oxidation is still where it's at (re: your uncouplers ideas, fibrates in theory but apparently not so much in practice).

And what's moxo?

Posts 7 and 11 on the moxo reference.

I get what you're saying WRT oxidation... Don't uncouplers do the exact same thing as lipolysis?

Uncoupling protein
From Wikipedia, the free encyclopedia
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A uncoupling protein is a proton channel which disrupts the gradient before it can be used to provide the energy for oxidative phosphorylation.[1]


Lipolysis
From Wikipedia, the free encyclopedia
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Lipolysis is the breakdown of fat stored in fat cells. During this process, free fatty acids are released into the bloodstream and circulate throughout the body. Ketones are produced, and are found in large quantities in ketosis (an adaptive metabolic state that occurs when insufficient carbohydrates are present in the diet). Lipolysis testing strips such as Ketostix are used to recognize ketosis.

doesn't look like it... I guess I never investigated the specifics of lipolysis.. Would have been nice before posting about a lipolytic agent... ass...


Due to wiki's explination of lipolysis it seems like a keto diet would be the most efficient way to utilize any lipolytic agent... Including this one.

Lots of steps involved in fat burning.

First, lipolysis = intra-adipocyte triglyceride hydrolysis (breaking one or more fatty acids from its glycerol backbone at the ester linkage.)
OR, alternatively, lipolysis from TG breakdown in digestion (doesn't have to be in an adipocyte already).

Anyway, then
Transfer outside the adipocyte and into the blood stream (is this passive? Don't remember)

Then,
Transfer into the mitochondria via carnitine palmitoyl transferase I and II (or is it CAT? the acetyltransferase works the same way)

Then,
beta oxidation through 4-5 steps. According to my biochem prof (dept head, hopefully he knows his shit), the rate limiting step here is the final reaction, catalyzed by thiolase, which unfortunately has no coenzymes or cofactors that he was aware of. Meaning that gene control is probably our best bet.

Important to note that insulin inhibits... well a lot of these steps. A lot of control mechanisms here. But, this has all been discussed by people infinitely more qualified than I -- look at some of the older discussions between spook, par, vain68, Layne (str8flexed), and a host of other geniuses.

EDIT: So to divide it into easier to swallow chunks, we have 3 big issues --

1 deriving FA from TG and getting it out of the fat cell (lipolysis)

2 getting it into the target tissues ie mitochondria in skeletal muscle or liver tissue,

3 "burning it" ie beta oxidation (called "beta" because it's broken down into 2 carbon chunks, as in alpha beta, as acetyl-coenzyme A, where it enters the TCA cycle for complete oxidation to CO2 and H20... explaining why FAs are predominantly found in even numbered carbon chains).

EDIT 2: excess fatty acids can be re-incorporated into adipocyte triglycerides via a process called "re-esterification."

Dash, heavy, ScottL -

I've posted a solution to our dilema in the anabolism thread, but not that I think about it this should really be posted in here considering it's not discussion of anabolism, it's of lipolysis...

here it is:




To expound on the beza + TZD wrt maybe including them in a stack with others (taken from a recently bumped CLA thread, props to Colin + Heavy Lifter)














In summary I'm suggesting for oxidative support without the (I'm gonna f'ing die feeling of uncouplers) beza+TZD+fish oil+CLA = super oxidation



This has been hypothesized at the limiter in lipolysis (says master senai dashforce) here:







Now here is dash's rundown on lipolysis:







Kinda beats the "try it find out" brotellegence being pimped lately on a pretty strict science driven board. I'll save my money on proven substances thank you.

J Pept Sci. 2008 Mar 28 [Epub ahead of print]Click here to read Links
Differences in the amount of lipolysis induced by atrial natriuretic peptide in small and large adipocytes.
Yu J, Yu HC, Kim KA, Kwon KB, Park JW, Kim SZ, Kim SH, Park BH.

Department of Biochemistry, Medical School and Institute for Medical Sciences, Chonbuk National University, Jeonju, Jeonbuk, 561‐756, Korea.

Atrial natriuretic peptide (ANP) is a 28-amino acid polypeptide that is primarily secreted by the heart. ANP is believed to be a hormone that regulates cardiovascular dynamics and renal functions; however, studies conducted in the past few decades revealed that ANP is also a potent lipolytic agent in human adipocytes that functions through the cGMP-dependent pathway. In this study, we separated human adipocytes within the same fat depot into small and large fractions using their floating properties and nylon filters of different pore sizes. Real-time PCR revealed that large adipocytes expressed higher mRNA levels of natriuretic peptide receptor (NPR)-A and hormone sensitive lipase, and binding studies showed that large adipocytes expressed more NPR-A on the membrane than small adipocytes. This finding was confirmed by the increase in the amount of glycerol that was released from adipocytes as the cell size increased. Taken together, these results clearly suggest that adipocyte size is an important determinant of ANP-stimulated lipolysis. Copyright © 2008 European Peptide Society and John Wiley & Sons, Ltd.

PMID: 18383440 [PubMed - as supplied by publisher]

Is Moxonidine available at U.S. Pharmacies? The pharmaceutical company, Solvay, does not list it.

J Hypertens. 2008 May;26(5):831-43.

Renin-angiotensin system, natriuretic peptides, obesity, metabolic syndrome, and hypertension: an integrated view in humans.

Sarzani R, Salvi F, Dessì-Fulgheri P, Rappelli A.

Department of Internal Medicine, Centre for Atherosclerosis and Metabolic Syndrome ("Hypertension Excellence Centre" of the European Society of Hypertension), University of Ancona - "Politecnica delle Marche", Ancona, Italy.

The obesity pandemic is closely related to hypertension and metabolic syndrome. Visceral adipose tissue plays a key role in the metabolic and cardiovascular complications of being overweight. The pathophysiological link between visceral adiposity and cardiometabolic complications focuses on insulin sensitivity, sympathetic nervous system, renin-angiotensin-aldosterone system (RAAS) and, only recently, on cardiac natriuretic peptide system (CNPS). RAAS and CNPS are endogenous antagonistic systems on sodium balance, cardiovascular system, and metabolism. The circulating RAAS is dysregulated in obese patients, and adipose tissue has a full local renin-angiotensin system that is active at local and systemic level. Adipocyte biology and metabolism are influenced by local renin-angiotensin system, with angiotensin II acting as a 'growth factor' for adipocytes. CNPS induces natriuresis and diuresis, reduces blood pressure, and, moreover, has powerful lipolytic and lipomobilizing activity in humans but not in rodents. In obesity, lower plasmatic natriuretic peptides levels with increasing BMI, waist circumference, and metabolic syndrome have been documented. Thus, reduced CNPS effects coupled with increased RAAS activity have a central role in obesity and its deadly complications. We propose herein an integrated view of the dysregulation of these two antagonistic systems in human obesity complicated with hypertension, metabolic syndrome, and increased cardiovascular risk.




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