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Lodhi lab identifies a new regulator of white fat levels in mice

Adipose tissue or body fat is a complex metabolic organ with a variety of functions. Two major types of adipose tissue are found in mammals: white adipose tissue (WAT) and brown adipose tissue (BAT). WAT primarily stores energy. In the context of obesity, WAT dramatically expands to store excess calories, contributing to metabolic consequences. Alternatively, BAT dissipates energy in the form of heat and is related to positive metabolic outcomes. New research from Dr. Irfan Lodhi’s laboratory published in Cell Reports on October 6, 2020 demonstrates that a protein named MED19 is important for the development and maintenance of white fat.

MED19 is a component of a protein complex called the Mediator, which transmits signals from gene-specific transcription factors to the basal transcriptional machinery. The authors demonstrate that genetic inactivation of MED19 blocks differentiation of white fat cells but not brown fat cells.  Moreover, they show that depletion of MED19 in mice promotes a dramatic loss of WAT and accumulation of fat in the liver, resulting in insulin resistance. Through a series of experiments aimed at identifying gene networks regulated by MED19, the authors discovered that MED19 is essential for mediating the activity of PPARg, a transcription factor critical for fat development. Future studies in the Lodhi lab will focus on understanding precisely how MED19 links signals from PPARg  to the basal transcriptional machinery to preferentially control white fat levels, which could potentially lead to identification a novel therapeutic strategy for treating obesity.

Dean JM, He A, Tan M, Wang J, Lu D, Razani B, Lodhi IJ. MED19 Regulates Adipogenesis and Maintenance of White Adipose Tissue Mass by Mediating PPARg-Dependent Gene Expression. Cell Reports 33, 108228, October 6, 2020