Regulated adipose tissue-specific expression of human in lipodystrophic -null mice results in regeneration of adipose tissue.

Genetic loss of in humans and mice results in congenital generalized lipodystrophy with near-total loss of adipose tissue and predisposition to develop insulin resistance, diabetes mellitus, hepatic steatosis, and hypertriglyceridemia. The mechanism by which deficiency results in loss of adipose tissue remains unknown. We studied this by re-expressing human (hAGPAT2) in -null mice, regulated by doxycycline. In both sexes of -null mice, adipose-tissue-specific re-expression of h resulted in partial regeneration of both white and brown adipose tissue (but only 30%-50% compared with wild-type mice), which had molecular signatures of adipocytes, including leptin secretion. Furthermore, the stromal vascular fraction cells of regenerated adipose depots differentiated only with doxycycline, suggesting the essential role of in adipocyte differentiation. Turning off expression of h resulted in total loss of regenerated adipose tissue, clear evidence that Agpat2 is essential for adipocyte differentiation .