Uncoupling of Obesity from Insulin Resistance Through a Targeted Mutation in <i>aP2</i> , the Adipocyte Fatty Acid Binding Protein

TLDR

Fatty acid binding proteins (FABPs) are small cytoplasmic proteins expressed in a tissue‑specific manner that bind fatty acids such as oleic and retinoic acid. Mice lacking the adipocyte fatty acid binding protein aP2 develop obesity without insulin resistance or diabetes and fail to upregulate adipose TNF‑α, indicating that aP2 links fatty acid metabolism to obesity‑related insulin resistance.

Abstract

Fatty acid binding proteins (FABPs) are small cytoplasmic proteins that are expressed in a highly tissue-specific manner and bind to fatty acids such as oleic and retinoic acid. Mice with a null mutation in aP2 , the gene encoding the adipocyte FABP, were developmentally and metabolically normal. The aP2 -deficient mice developed dietary obesity but, unlike control mice, they did not develop insulin resistance or diabetes. Also unlike their obese wild-type counterparts, obese aP2 −/− animals failed to express in adipose tissue tumor necrosis factor-α (TNF-α), a molecule implicated in obesity-related insulin resistance. These results indicate that aP2 is central to the pathway that links obesity to insulin resistance, possibly by linking fatty acid metabolism to expression of TNF-α.