A-ZIP/F-1 mice lacking white fat: a model for understanding lipoatrophic diabetes

The A-ZIP/F-1 mouse is lacking virtually all white adipose tissue. Like hum ans with extensive deficiencies of adipose tissue, the A-ZIP/F-1 mice devel op a severe form of insulin resistant diabetes. We have studied the physiol ogy of the A-ZIP/F-1 mice. Their adaptation to fasting is notable for its r apidity and the use of torpor, a hibernation-like state, to minimize energy needs. Transplantation of adipose tissue reversed the metabolic manifestat ions in the mice, demonstrating that the lack of adipose tissue is the caus e of the insulin resistance. Leptin replacement is not very effective in re versing the diabetes of the A-ZIP/F-1 mice, which contrasts with its effica cy in the aP2-SREBP-1c mouse.