The Farmer group is interested in identifying mechanisms regulating adipose tissue formation and function. There are three major programs: 1) Role of Myocardin related transcription factor (MRTFA), the transcriptional coactivator of SRF (serum response factor) in regulating recruitment of perivascular progenitors in adipose tissue to adipocytes (white and beige) and myofibroblasts. We have recently shown that absence of MRTFA in mice protects against diet-induced insulin resistance by enhancing energy expenditure due to beige adipocyte formation. Its absence also prevents obesity-induced adipose fibrosis by preventing recruitment of progenitors to collagen-producing myofibroblasts. 2) Potential of post-translational modification of PPAR as an alternative mechanism to combat obesity-related disorders. Our studies have recently shown that phosphorylation of S273 in the ligand-binding domain of PPAR not only regulates insulin sensitivity (Spiegelman group), but also controls the conversion of mature white adipocytes to energy expending beige/brite adipocytes. Present investigations include identifying the factors that coregulate the browning activity of PPAR activity in response to dephosphorylation of S273. 3) The role of perivascular adipose tissue (PVAT) in regulating the health of thoracic aorta. Thoracic PVAT consists of brown-like adipocytes that are multi-locular and express UCP-1. Abdominal PVAT is composed of white adipocytes, which resemble those present in visceral adipose depots. Investigations include identifying the progenitors giving rise to these PVAT depots and defining the mechanisms control brown versus white adipocyte gene expression.
1. McDonald ME, Li C, Bian H, Smith BD, Layne MD and Farmer SR. (2015) Myocardin Related Transcription Factor Regulates Conversion of Progenitors to Beige Adipocytes. Cell. 160:105-18.
2. Bian H, Lin JZ, Li C and Farmer SR (2016). Myocardin Related Transcription Factor Regulates the Fate of Bone Marrow Mesenchymal Stem Cells and its Absence in Mice leads to Osteopenia. Mol Metab. 5:970-979.
3. Wang H, Liu L, Lin JZ, Aprahamian T and Farmer SR. (2016) Browning of white adipose tissue with roscovitine induces a distinct population of UCP1+ adipocytes. Cell Metab. 24:835-847.
4. Lin, JZ, Rabhi, N and Farmer, SR. (2018) Myocardin-Related Transcription Factor A Promotes Recruitment of ITGA5+ Profibrotic Progenitors during Obesity-Induced Adipose Tissue Fibrosis. Cell Reports,23:1977-1987.