Regulation of PPARγ and obesity by agouti/melanocortin signaling in adipocytes
To study the potential biological role of agouti/melanocortin signaling in human adipose tissue, we engineered transgenic mice to overexpress agouti in adipose tissue. The aP2-agouti transgenic mice become significantly heavier than littermates. The increased body weight is maintained at approximately 15% above nontransgenic mice through 20 weeks and is caused by increased fat mass. The obesity is increased by a high-fat diet. There is no change in food intake in the aP2-agouti mice suggesting changes in energy utilization. A possible mechanism is that the agouti/melanocortin signaling regulates levels of PPARγ. PPARγ functions as a major regulator of adipocyte differentiation and as a receptor for the antidiabetic thiazolidinediones. Agouti increases PPARγ protein levels in differentiated 3T3-L1 adipocytes, and PPARγ expression is elevated in the fat pads of the aP2-agouti transgenic mice. The modest weight gain observed in the transgenic mice suggests that hypothalamic pathways regulating food intake are intact and the observed adiposity is within ranges that can be achieved by a paracrine mechanism at the adipocyte level.
Publication Source (Journal or Book title)
Annals of the New York Academy of Sciences
Mynatt, R., & Stephens, J. (2003). Regulation of PPARγ and obesity by agouti/melanocortin signaling in adipocytes. Annals of the New York Academy of Sciences, 994, 141-146. https://doi.org/10.1111/j.1749-6632.2003.tb03173.x