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Regulation of Metabolic Responses by Adipocyte/ Macrophage Fatty Acid–Binding Proteins in Leptin-Deficient Mice
| Content Provider | Paperity |
|---|---|
| Author | Cao, Haiming Maeda, Kazuhisa Kim, Hyo-jeong Gorgun, Cem Z. Park, So-young Shulman, Gerald I. Hotamisligil, Gökhan S. Kim, Jason K. |
| 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 liver 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 liver 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 liver 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. |
| Starting Page | 1915 |
| Ending Page | 1922 |
| File Format | HTM / HTML |
| ISSN | 00121797 |
| DOI | 10.2337/db05-1496 |
| Issue Number | 7 |
| Journal | Diabetes |
| Volume Number | 55 |
| e-ISSN | 1939327X |
| Language | English |
| Publisher | American Diabetes Association |
| Publisher Date | 2006-07-01 |
| Access Restriction | Open |
| Subject Keyword | Srebp, sterol regulatory element–binding protein Fabp, fatty acid–binding protein Ampk, amp-activated kinase Hgp, hepatic glucose production Scd-1, stearoyl-coa desaturase-1 |
| Content Type | Text |
| Resource Type | Article |
| Subject | Endocrinology, Diabetes and Metabolism Internal Medicine |
