UNCOUPLING OF OBESITY FROM INSULIN-RESISTANCE THROUGH A TARGETED MUTATION IN AP2, THE ADIPOCYTE FATTY-ACID-BINDING PROTEIN

Fatty acid binding proteins (FABPs) are small cytoplasmic proteins tha t are expressed in a highly tissue-specific manner and bind to fatty a cids such as oleic and retinoic acid. Mice with a null mutation in aP2 , the gene encoding the adipocyte FABP, were developmentally and metab olically normal. The aP2-deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabe tes. Also unlike their obese wild-type counterparts, obese aP2(-/-) an imals failed to express in adipose tissue tumor necrosis factor-alpha (TNF-alpha), a molecule implicated in obesity-related insulin resistan ce. These results indicate that aP2 is central to the pathway that lin ks obesity to insulin resistance, possibly by linking fatty acid metab olism to expression of TNF-alpha.