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.
- Dance YW, MC Obenreder, AJ Seibel, T Meshulam, JW Ogony, N Lahiri, L Pacheco-Spann, DC Radisky, MD Layne, SR Farmer, CM Nelson, J Tien. Adipose Cells Induce Escape from an Engineered Human Breast Microtumor Independently of their Obesity Status. Cellular and Molecular Bioengineering (2022)
- Rabhi N, Desevin K, Belkina AC, Tilston-Lunel A, Varelas X, Layne MD, Farmer SR. Obesity-induced senescent macrophages activate a fibrotic transcriptional program in adipocyte progenitors. Life Sci Alliance. 2022 May; 5(5).PMID: 35181634.
- Rabhi N, Farmer SR. Unraveling the complexity of thermogenic remodeling of white fat reveals potential antiobesity therapies. Genes Dev. 2021 Nov 1;35(21-22):1395-1397. doi: 10.1101/gad.349053.121.Jafari N, Kolla M, Meshulam T, Shafran JS, Qiu Y,
- Casey AN, Pompa IR, Ennis CS, Mazzeo CS, Rabhi N, Farmer SR, Denis GV. Adipocyte-derived exosomes may promote breast cancer progression in type 2 diabetes. Sci Signal. 2021 Nov 23;14(710):eabj2807. doi: 10.1126/scisignal.abj2807. PMID: 34813359
- Biagi C, Cury SS, Alves CP, Rabhi N, Silva WA, Farmer SR, Carvalho RF, Batista ML. Multidimensional Single-Nuclei RNA-Seq Reconstruction of Adipose Tissue Reveals Adipocyte Plasticity Underlying Thermogenic Response. Cells 2021, 10, 3073.
- Rabhi N, Desevin K, Cortez BN, Hekman R, Lin JZ, Emili A, Farmer SR. The cyclin dependent kinase inhibitor Roscovitine prevents diet-induced metabolic disruption in obese mice. Sci Rep. 2021 Oct 13;11(1):20365. PMID: 34645915
- Wang D, Rabhi N, Yet SF, Farmer SR, Layne MD. Aortic carboxypeptidase-like protein regulates vascular adventitial progenitor and fibroblast differentiation through myocardin related transcription factor A. Sci Rep. 2021 Feb 17; 11(1):3948. PMID: 33597582
- Batista ML, Meshulam T, Desevin K, Rabhi N, Farmer SR. Three-Dimensional Adipocyte Culture as a Model to Study Cachexia-Induced White Adipose Tissue Remodeling. J Vis Exp. 2021 01 18; (167). PMID: 33522508
- Rabhi N, Belkina AC, Desevin K, Cortez BN, Farmer SR. Shifts of Immune Cell Populations Differ in Response to Different Effectors of Beige Remodeling of Adipose Tissue. iScience. 2020 Dec 18; 23(12):101765. PMID: 33294778
- Kim S, Rabhi N, Blum BC, Hekman R, Wynne K, Emili A, Farmer S, Schlezinger JJ. Triphenyl phosphate is a selective PPARg modulator that does not induce brite adipogenesis in vitro and in vivo. Arch Toxicol. 2020 09; 94(9):3087-3103. PMID: 32683515
- Jones JEC, Rabhi N, Orofino J, Gamini R, Perissi V, Vernochet C, Farmer SR. The Adipocyte Acquires a Fibroblast-Like Transcriptional Signature in Response to a High Fat Diet. Sci Rep. 2020 Feb 11; 10(1):2380. PMID: 32047213
- Jash S, Banerjee S, Lee MJ, Farmer SR, Puri V. CIDEA Transcriptionally Regulates UCP1 for Britening and Thermogenesis in Human Fat Cells. iScience. 2019 Oct 25; 20:73-89. PMID: 31563853
- Rabhi N, Farmer SR. Adipose Progenitor Cells Contribute to Lipid Spillover during Obesity. Trends Endocrinol Metab. 2019 Jul; 30(7):416-418. PMID: 31153731
- Farmer SR. Boning Up on Irisin. N Engl J Med. 2019 04 11; 380(15):1480-1482. PMID: 30970196
- 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
Complete list can be found at BU Profiles