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 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.
Hotamisligil
G S
GS
Department of Nutrition, Harvard School of Public Health, 665 Huntington Avenue, Boston, MA 02115, USA. CA 92093, USA.
Johnson
R S
RS
Distel
R J
RJ
Ellis
R
R
Papaioannou
V E
VE
Spiegelman
B M
BM
D000273:Adipose Tissue / Q000378:metabolism*; D000818:Animals; D001786:Blood Glucose / Q000378:metabolism; D002352:Carrier Proteins / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D004041:Dietary Fats / Q000008:administration & dosage; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids / Q000378:metabolism*; D005260:Female; D005786:Gene Expression Regulation; D018390:Gene Targeting; D005951:Glucose Tolerance Test; D006706:Homeostasis; D007328:Insulin / Q000097:blood; D007333:Insulin Resistance; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D018996:Myelin P2 Protein / Q000235:genetics / Q000378:metabolism / Q000502:physiology*; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D009765:Obesity / Q000378:metabolism*; D014280:Triglycerides / Q000097:blood; D014409:Tumor Necrosis Factor-alpha / Q000096:biosynthesis* / Q000235:genetics
D001786:Blood Glucose; D002352:Carrier Proteins; D004041:Dietary Fats; C082667:Fabp5 protein, mouse; C086936:Fabp7 protein, mouse; D000071438:Fatty Acid-Binding Protein 7; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D007328:Insulin; D018996:Myelin P2 Protein; D009363:Neoplasm Proteins; D009419:Nerve Tissue Proteins; D014280:Triglycerides; D014409:Tumor Necrosis Factor-alpha