A glucocorticoid- and diet-responsive pathway toggles adipocyte precursor cell activity in vivo

Excess body fat, particularly in the visceral white adipose depot, poses serious health risks. A cellular mechanism that contributes to the expansion of adipose tissue is the increased differentiation of adipocyte precursor cells into mature adipocytes. Wong et al . found that glucocorticoid exposure or a high-fat diet altered the abundance of an extracellular protein called ADAMTS1 in adipocytes in an adipose depot–specific manner in mice. Increased ADAMTS1 abundance was associated with decreased adipogenesis, whereas decreased ADAMTS1 abundance was associated with increased adipogenesis. Human volunteers who increased their caloric intake showed increased expression of ADAMTS1 in adipose tissue. Exposing adipocyte precursor cells to ADAMTS1 protein increased their proliferation and prevented their differentiation, and mice that overexpressed Adamts1 in adipose tissue had smaller adipose depots. These results suggest that ADAMTS1 could be administered to prevent obesity in response to diet or glucocorticoid administration.