Surgical implantation of adipose tissue reverses diabetes in lipoatrophic mice

In lipoatrophic diabetes, a lack of fat is associated with insulin resistan ce and hyperglycemia. This is in striking contrast to the usual association of diabetes with obesity. To understand the underlying mechanisms, we tran splanted adipose tissue into A-ZIP/F-1 mice, which have a severe form of li poatrophic diabetes. Transplantation of wild-type fat reversed the hypergly cemia, dramatically lowered insulin levels, and improved muscle insulin sen sitivity, demonstrating that the diabetes in A-ZIP/F-1 mice is caused by th e lack of adipose tissue. All aspects of the A-ZIP/F-1 phenotype including hyperphagia, hepatic steatosis, and somatomegaly were either partially or c ompletely reversed. However, the improvement in triglyceride and FFA levels was modest. Donor fat taken from parametrial and subcutaneous sites was eq ually effective in reversing the phenotype. The beneficial effects of trans plantation were dose dependent and required near-physiological amounts of t ransplanted fat. Transplantation of,genetically modified fat into A-ZIP/F-1 mice is a new and powerful technique for studying adipose physiology and t he metabolic and endocrine communication between adipose tissue and the res t of the body.