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- Title
Regulation of Metabolic Responses by Adipocyte/Macrophage Fatty Acid--Binding Proteins in Leptin-Deficient Mice.
- Authors
Cao, Haiming; Maeda, Kazuhisa; Gorgun, Cem Z.; Kim, Hyo-Jeong; Park, So-Young; Shulman, Gerald I.; Kim, Jason K.; Hotamisligil, Gökhan S.
- Abstract
Fatty acid-binding proteins (FABPs) are cytosolic fatty acid chaperones that play a critical role in systemic regulation of lipid and glucose metabolism. In animals lacking the adipocyte/macrophage FABP isoforms aP2 and mal1, there is strong protection against diet-induced obesity, insulin resistance, type 2 diabetes, fatty liver disease, and hypercholesterolemic atherosclerosis. On high-fat diet, FABP-deficient mice also exhibit enhanced muscle AMP-activated kinase (AMPK) and reduced fiver stearoyl-CoA desaturase-1 (SCD-1) activities. Here, we performed a cross between aP2-/-, mal1-/-, and leptin-deficient (ob/ob) mice to elucidate the role of leptin action on the metabolic phenotype of aP2-mal1 deficiency. The extent of obesity in the ob/ob-aP2-mal1-/- mice was comparable with ob/ob mice. However, despite severe obesity, ob/ob-aP2-mal1-/- mice remained euglycemic and demonstrated improved peripheral insulin sensitivity. There was also a striking protection from fiver fatty infiltration in the ob/ob-aP2-mal1-/- mice with strong suppression of SCD-1 activity. On the other hand, the enhanced muscle AMPK activity in aP2-mal1-/- mice was lost in the ob/ob background. These results indicated that both decreased body weight and enhanced muscle AMPK activity in aP2-mal1-/- mice are potentially leptin dependent but improved systemic insulin sensitivity and protection from fiver fatty infiltration are largely unrelated to leptin action and that insulin-sensitizing effects of FABP deficiency are, at least in part, independent of its effects on total-body adiposity. Diabetes 55:1915-1922, 2006
- Subjects
FATTY acid-binding proteins; MOLECULAR chaperones; METABOLISM; GLUCOSE; LIPIDS
- Publication
Diabetes, 2006, Vol 55, Issue 7, p1915
- ISSN
0012-1797
- Publication type
Abstract
- DOI
10.2337/db05-1496