Stephen R. Farmer
Boston University School of Medicine
Silvio Conte Building, Office: K602; Lab: K606
72 E. Concord Street
Boston, MA 02118
BSc Hons I, Liverpool University, England
PhD National Institute for Medical Research, London, England
| Hong Wang
| Hejiao Bian
Obesity has now reached pandemic proportions, resulting in dramatic increases in the occurrence of its associated disorders including diabetes and cardiovascular disease. Understanding the processes and metabolic perturbations that contribute to the expansion of adipose depots accompanying obesity is critical for the development of appropriate therapeutics. Expansion of white adipose (WAT) tissue depots particularly the intra-abdominal depots contribute to insulin resistence and inflammation that lead to type 2 diabetes, whereas brown adipose (BAT) resists expansion because it oxidizes lipids and, consequently, it is associated with an healthier phenotype. Our studies are focused on identifying the mechanisms regulating the formation and function of white and brown adipocytes (fat cells) using a variety of experimental approaches including overexpression and knock down of specific nuclear factors that we consider to be likely regulators of these processes in cells in culture as well as in mice. At present our focus is on nuclear factors that modulate the activity of the two principal regulators of adipogenesis (fat cell differentiation) peroxisome proliferator-activated receptor gamma (PPARg) and CCAAT/enhancer binding proteins alpha, beta and delta (C/EBPs). We are particularly interested in identifying the factors regulating commitment of mesenchymal progenitors to the adipogenic lineage and are adopting a variety of approaches to achieve this goal, which includes gene profiling to discover novel regulators as well as investigating the role of selected candidate genes.
- Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Liew CW, Boucher J, Cheong JK, Vernochet C, Koh HJ, Mallol C, Townsend K, Langin D, Kawamori D, Hu J, Tseng YH, Hellerstein MK, Farmer SR, Goodyear L, Doria A, Blüher M, Hsu SI, Kulkarni RN. Nat Med. 2013 Feb;19(2):217-26.
- Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia. Batista ML Jr, Neves RX, Peres SB, Yamashita AS, Shida CS, Farmer SR, Seelaender M. J Endocrinol. 2012 Dec;215(3):363-373.
- Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Pparγ. Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, Rosenbaum M, Zhao Y, Gu W, Farmer SR, Accili D. Cell. 2012 Aug 3;150(3):620-32.
- Recruitment of brown adipose tissue as a therapy for obesity-associated diseases. Boss O, Farmer SR. Front Endocrinol (Lausanne). 2012;3:14.
- Roles for peroxisome proliferator-activated receptor γ (PPARγ) and PPARγ coactivators 1α and 1β in regulating response of white and brown adipocytes to hypoxia. Pino E, Wang H, McDonald ME, Qiang L, Farmer SR. J Biol Chem. 2012 May 25;287(22):18351-8.
- Karki S, Chakrabarti P, Huang G, Wang H, Farmer SR, Kandror KV. The multi-level action of fatty acids on adiponectin production by fat cells. PLoS One. 2011;6:e28146. PMID:22140527
- Chakrabarti P, English T, Karki S, Qiang L, Tao R, Kim J, Luo Z, Farmer SR, Kandror KV. SIRT1 controls lipolysis in adipocytes via FOXO1-mediated expression of ATGL. J Lipid Res. 52:1693-701, 2011.
- Vernochet C, McDonald ME, Farmer SR. Brown Adipose Tissue: a promising target to combat obesity. Drug News Perspect. 23:409-17, 2010.
- Vernochet C, Davis KE, Scherer PE, Farmer SR. Mechanisms regulating repression of haptoglobin production by peroxisome proliferator-activated receptor-gamma ligands in adipocytes Endocrinology. 151:586-94, 2010.
- Vernochet C, Peres SB, Davis KE, McDonald ME, Qiang L, Wang H, Scherer PE, Farmer SR. C/EBPalpha and the corepressors CtBP1 and CtBP2 regulate repression of select visceral white adipose genes during induction of the brown phenotype in white adipocytes by peroxisome proliferator-activated receptor gamma agonists. Mol. Cell. Biol. 29:4714-28, 2009.
- Farmer SR. Obesity: Be cool, lose weight. Nature 458:839-840, 2009.
- Farmer SR. Brown fat and skeletal muscle: unlikely cousins? Cell 134:726-727,2008.
- Farmer SR. Molecular Determinants of Brown Adipocyte Formation and Function. Genes & Dev. 22:1269-75, 2008
- Wang H, Qiang L, Farmer SR. Identification of a domain within peroxisome proliferator-activated receptor gamma regulating expression of a group of genes containing fibroblast growth factor 21 that are selectively repressed by SIRT1 in adipocytes. Mol Cell Biol 28: 188-200, 2008.
- Bezy O, Vernochet C, Gesta S, Farmer SR, Kahn CR. TRB3 blocks adipocyte differentiation through the inhibition of C/EBPb transcriptional activity. Mol. Cell. Biol. 27:6818-31. 2007.
- Qiang L, Wang H, Farmer SR. Adiponectin secretion is regulated by the ER oxidoreductase Ero1-La and changes in PPARg and SIRT1 activity. Mol. Cell. Biol. 27:4698-4707. 2007.
- Liu J, Wang H, Zuo Y, Farmer SR. A Functional Interaction between Peroxisome Proliferator-Activated Receptor g and b-Catenin. Mol. Cell. Biol. 26:5827-37. 2006.
- Farmer SR. Transcriptional Control of Adipocyte Formation. Cell Metab. 4: 263-73. 2006.