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 resistance 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.
Nabil Rabhi – Postdoctoral Associate
Kathleen Desivin – Research Technician
- Henriques F, Lopes MA, Franco FO, Knobl P, Santos KB, Bueno LL, Correa VA, Bedard AH, Guilherme A, Birbrair A, Peres SB, Farmer SR, Batista ML. Toll-Like Receptor-4 Disruption Suppresses Adipose Tissue Remodeling and Increases Survival in Cancer Cachexia Syndrome. Sci Rep. 2018 Dec 21; 8(1):18024. PMID: 30575787.
- Jager M, Lee MJ, Li C, Farmer SR, Fried SK, Layne MD. Aortic carboxypeptidase-like protein enhances adipose tissue stromal progenitor differentiation into myofibroblasts and is upregulated in fibrotic white adipose tissue. PLoS One. 2018; 13(5):e0197777. PMID: 29799877.
- Lin JZ, Rabhi N, Farmer SR. Myocardin-Related Transcription Factor A Promotes Recruitment of ITGA5+ Profibrotic Progenitors during Obesity-Induced Adipose Tissue Fibrosis. Cell Rep. 2018 May 15; 23(7):1977-1987. PMID: 29768198.
- Wang H, Liu L, Lin JZ, Aprahamian TR, Farmer SR. Browning of white adipose tissue with roscovitine induces a distinct population of UCP1+ adipocytes. Cell Metab. 2016 Dec 13;24(6):835-847. View in: Pubmed
- Bian H, Lin JZ, Li C, Farmer SR. Myocardin-related transcription factor A (MRTFA) regulates the fate of bone marrow mesenchymal stem cells and its absence in mice leads to osteopenia. Mol Metab. 2016 Oct; 5(10):970-9. PMID: 27689009. View in: PubMed
- Lin JZ, Farmer SR. LSD1-a pivotal epigenetic regulator of brown and beige fat differentiation and homeostasis. Genes Dev. 2016 Aug 15; 30(16):1793-5. PMID: 27601528. View in: PubMed
- Beluzi M, Peres SB, Henriques FS, Sertié RA, Franco FO, Santos KB, Knobl P, Andreotti S, Shida CS, Neves RX, Farmer SR, Seelaender M, Lima FB, Batista ML. Pioglitazone treatment increases survival and prevents body weight loss in tumor-bearing animals: possible anti-cachectic effect. PLoS One. 2015; 10(3):e0122660. PMID: 25807446. View in: PubMed
McDonald ME, Li C, Bian H, Smith BD, Layne MD, Farmer SR. Myocardin-related transcription factor A regulates conversion of progenitors to beige adipocytes. Cell. 2015 Jan 15; 160(1-2):105-18. PMID: 25579684.
View in: PubMed
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. Ablation of TRIP-Br2, a regulator of fat lipolysis, thermogenesis and oxidative metabolism, prevents diet-induced obesity and insulin resistance. Nat Med. 2013 Feb; 19(2):217-26. PMID: 23291629.
View in: PubMed
Batista ML, Neves RX, Peres SB, Yamashita AS, Shida CS, Farmer SR, Seelaender M. Heterogeneous time-dependent response of adipose tissue during the development of cancer cachexia. J Endocrinol. 2012 Dec; 215(3):363-73. PMID: 23033362.
View in: PubMed
Qiang L, Wang L, Kon N, Zhao W, Lee S, Zhang Y, Rosenbaum M, Zhao Y, Gu W, Farmer SR, Accili D. Brown remodeling of white adipose tissue by SirT1-dependent deacetylation of Ppar?. Cell. 2012 Aug 3; 150(3):620-32. PMID: 22863012.
View in: PubMed
Complete list can be found at BU Profiles