Endocrinology. 2006 Nov;147(11):5325-32. Epub 2006 Jul 13. Links
Remodeling of white adipose tissue after retinoic acid administration in mice.Mercader J, Ribot J, Murano I, Felipe F, Cinti S, Bonet ML, Palou A.
Laboratory of Molecular Biology, Nutrition and Biotechnology, University of the Balearic Islands, 07122 Palma de Mallorca, Spain.

A reduced brown adipose phenotype in white adipose tissue (WAT) may contribute to obesity and type 2 diabetes in humans. Retinoic acid, the carboxylic form of vitamin A, triggers in rodents a reduction of body weight and adiposity and an increased expression of uncoupling proteins in brown adipose tissue and skeletal muscle. In this study, we investigated possible remodeling effects of all-trans retinoic acid (ATRA) in WAT depots. Changes in the expression of genes related to thermogenesis and fatty acid oxidation and levels of phosphorylated retinoblastoma protein were analyzed in WAT depots of adult NMRI male mice acutely injected with ATRA or vehicle, together with biometric and blood parameters. Body fat loss after ATRA treatment was unaccompanied by any increase in circulating nonesterified fatty acids or ketone bodies and accompanied by increased rectal temperature. The treatment triggered an up-regulation of the mRNA levels of uncoupling proteins 1 and 2, peroxisome proliferator-activated receptor gamma coactivator-1alpha, peroxisome proliferator-activated receptor alpha, muscle- and liver-type carnitine palmitoyltransferase 1, and subunit II of cytochrome oxidase in different WAT depots. Levels of phosphorylated retinoblastoma protein in WAT depots were increased after ATRA treatment. Adipocyte size was reduced, and the number of multilocular adipocytes was increased in inguinal WAT of ATRA-treated mice. The results indicate that ATRA favors the acquisition of brown adipose tissue-like properties in WAT. Understanding the mechanisms and effectors involved in the remodeling of WAT can contribute to new avenues of prevention and treatment of obesity and type 2 diabetes.

PMID: 16840543 [PubMed - indexed for MEDLINE]

Cell Physiol Biochem. 2007;20(6):1061-72. Epub 2007 Oct 30. Links
All-trans retinoic acid increases oxidative metabolism in mature adipocytes.Mercader J, Madsen L, Felipe F, Palou A, Kristiansen K, Bonet ML.
Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illws Balears, Palma de Mallorca, Spain.

BACKGROUND/AIMS: In rodents, retinoic acid (RA) treatment favors loss of body fat mass and the acquisition of brown fat features in white fat depots. In this work, we sought to examine to what extent these RA effects are cell autonomous or dependent on systemic factors. METHODS: Parameters of lipid metabolism and related gene expression were analyzed in differentiated 3T3-L1 adipocytes after exposure to RA or vehicle. RESULTS: Treatment with RA resulted in decreased cellular triacylglycerol content and increased basal lipolysis and fatty acid oxidation rate. At the mRNA level, RA treatment led to a reduced expression of adipogenic/lipogenic transcription factors (peroxisome proliferator-activated receptor gamma, CCAAT/enhancer-binding protein alpha, rexinoid receptor alpha) and two purported suppressors of lipolysis and oxidative metabolism (CIDEA and receptor-interacting protein 140), and to an increased expression of proteins favoring fat oxidation (peroxisome proliferator-activated receptor gamma coactivator-1alpha, uncoupling protein 2, fasting-induced adipose factor, enzymes of mitochondrial fatty acid oxidation). These changes paralleled inactivation of the retinoblastoma protein and were preceded by an early RA-induced phosphorylation of p38 mitogen-activated protein kinase. UCP1 expression was not induced. CONCLUSION: The results indicate that RA directly favors remodeling of mature 3T3-L1 adipocytes in culture toward increased oxidative metabolism.

PMID: 17975308 [PubMed - indexed for MEDLINE]

Am J Physiol Endocrinol Metab. 2006 May;290(5):E916-24. Epub 2005 Dec 20. Links
Molecular mechanism of 1,25-dihydroxyvitamin D3 inhibition of adipogenesis in 3T3-L1 cells.Kong J, Li YC.
Dept. of Medicine, Univ. of Chicago, 5841 S. Maryland Ave., Chicago, IL 60637, USA.

We have investigated the molecular mechanism whereby 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] inhibits adipogenesis in vitro. 1,25(OH)2D3 blocks 3T3-L1 cell differentiation into adipocytes in a dose-dependent manner; however, the inhibition is ineffective 24-48 h after the differentiation is initiated, suggesting that 1,25(OH)2D3 inhibits only the early events of the adipogenic program. Treatment of 3T3-L1 cells with 1,25(OH)2D3 does not block the mitotic clonal expansion or C/EBPbeta induction; rather, 1,25(OH)2D3 blocks the expression of C/EBPalpha, peroxisome proliferator-activated receptor-gamma (PPARgamma), sterol regulatory element-binding protein-1, and other downstream adipocyte markers. The inhibition by 1,25(OH)2D3 is reversible, since removal of 1,25(OH)2D3 from the medium restores the adipogenic process with only a temporal delay. Interestingly, although the vitamin D receptor (VDR) protein is barely detectable in 3T3-L1 preadipocytes, its levels are dramatically increased during the early phase of adipogenesis, peaking at 4-8 h and subsiding afterward throughout the rest of the differentiation program; 1,25(OH)2D3 treatment appears to stabilize the VDR protein levels. Consistently, adenovirus-mediated overexpression of human (h) VDR in 3T3-L1 cells completely blocks the adipogenic program, confirming that VDR is inhibitory. Inhibition of adipocyte differentiation by 1,25(OH)2D3 is ameliorated by troglitazone, a specific PPARgamma antagonist; conversely, hVDR partially suppresses the transacting activity of PPARgamma but not of C/EBPbeta or C/EBPalpha. Moreover, 1,25(OH)2D3 markedly suppresses C/EBPalpha and PPARgamma mRNA levels in mouse epididymal fat tissue culture. Taken together, these data indicate that the blockade of 3T3-L1 cell differentiation by 1,25(OH)2D3 occurs at the postclonal expansion stages and involves direct suppression of C/EBPalpha and PPARgamma upregulation, antagonization of PPARgamma activity, and stabilization of the inhibitory VDR protein.

PMID: 16368784 [PubMed - indexed for MEDLINE]

Obesity (Silver Spring). 2008 Mar;16(3):585-91. Epub 2008 Jan 17. Links
Retinoic Acid treatment increases lipid oxidation capacity in skeletal muscle of mice.Amengual J, Ribot J, Bonet ML, Palou A.
[1] 1Laboratory of Molecular Biology, Nutrition and Biotechnology, Universitat de les Illes Balears, Palma de Mallorca, Spain [2] 2CIBER Fisiopatología de la Obesidad y Nutrición (CB06/03), Instituto de Salud Carlos III, Spain.

Objective:All-trans retinoic acid (ATRA), a carboxylic form of vitamin A, favors in mice a mobilization of body fat reserves that correlates with an increment of oxidative and thermogenic capacity in adipose tissues. The objective of this study has been to investigate the effect of ATRA treatment on skeletal muscle capacity for fatty-acid catabolism.Methods and Procedures:Tissue composition and gene expression related to lipid and oxidative metabolism were analyzed in skeletal muscle of mice acutely treated with ATRA or vehicle (olive oil).Results:ATRA treatment triggered a dose-dependent increase in the muscle mRNA expression levels of selected enzymes, transporters and transcription factors involved in fatty-acid oxidation, respiration, and thermogenesis namely: muscle-type carnitine palmitoyltransferase 1, acyl CoA oxidase 1, subunit II of cytochrome oxidase, uncoupling protein 3, peroxisome proliferator-activated receptor-gamma co-activator -1alpha and peroxisome proliferator-activated receptor-delta (PPARdelta). The treatment also resulted in the upregulation of the mRNA levels of acetyl-CoA carboxylase 2 (ACC2), a key regulatory enzyme for mitochondrial fatty-acid oxidation in muscle. Skeletal muscle protein levels of PPARdelta and retinoid X receptor gamma, a partner for many nuclear receptors involved in lipid metabolism, were increased after ATRA treatment. Muscle lipid content was decreased.Discussion:These results indicate that ATRA treatment increases the capacity of skeletal muscle for fatty-acid oxidation. Knowledge of nutrients or nutrient-derivatives capable of enhancing oxidative metabolism in muscle and other tissues can contribute to new avenues of prevention and treatment of obesity and related disorders.Obesity (2008) 16 3, 585-591. doi:10.1038/oby.2007.104.

PMID: 18239600 [PubMed - in process]

if you believe me or anyone else has used to kind of protocol I'm hypothesizing about then maybe my brains aren't the ones you should be concerned about.

I would however love to hear any input you could add on the subject.

No, I mean seriously. I think I remember reading about some real problematic side effects with retinoin that screws with some part of the brain. Weren't there people who took it and now are permanently depressed or am I thinking of a different drug?

jake, what i read from people taking fuco said that it took some time to work and then for those that did get an effect their pee became rancid smelling. Interesting.

I am gonna get some from CNW, see what happens.