Uncoupling of obesity from insulin resistance through a targeted mutation in aP2, the adipocyte fatty acid binding protein

Science. 1996 Nov 22;274(5291):1377-9. doi: 10.1126/science.274.5291.1377.


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-alpha (TNF-alpha), 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-alpha.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adipose Tissue / metabolism*
  • Animals
  • Blood Glucose / metabolism
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism
  • Carrier Proteins / physiology*
  • Dietary Fats / administration & dosage
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Fatty Acids / metabolism*
  • Female
  • Gene Expression Regulation
  • Gene Targeting
  • Glucose Tolerance Test
  • Homeostasis
  • Insulin / blood
  • Insulin Resistance*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Mutation
  • Myelin P2 Protein / genetics
  • Myelin P2 Protein / metabolism
  • Myelin P2 Protein / physiology*
  • Neoplasm Proteins*
  • Nerve Tissue Proteins*
  • Obesity / metabolism*
  • Triglycerides / blood
  • Tumor Necrosis Factor-alpha / biosynthesis*
  • Tumor Necrosis Factor-alpha / genetics


  • Blood Glucose
  • Carrier Proteins
  • Dietary Fats
  • Fabp5 protein, mouse
  • Fabp7 protein, mouse
  • Fatty Acid-Binding Protein 7
  • Fatty Acid-Binding Proteins
  • Fatty Acids
  • Insulin
  • Myelin P2 Protein
  • Neoplasm Proteins
  • Nerve Tissue Proteins
  • Triglycerides
  • Tumor Necrosis Factor-alpha