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Adipocyte/macrophage fatty acid binding proteins control integrated metabolic responses in obesity and diabetes.

Maeda K, Cao H, Kono K, Gorgun CZ, Furuhashi M, Uysal KT, Cao Q, Atsumi G, Malone H, Krishnan B, Minokoshi Y, Kahn BB, Parker RA, Hotamisligil GS

Department of Genetics and Complex Diseases, Harvard School of Public Health, Boston, Massachusetts 02115, USA.

Fatty acid binding proteins (FABPs) are cytosolic fatty acid chaperones whose biological role and mechanisms of action are not well understood. Here, we developed mice with targeted mutations in two related adipocyte FABPs, aP2 and mal1, to resolve their role in systemic lipid, glucose, and energy metabolism. Mice lacking aP2 and mal1 exhibited a striking phenotype with strong protection from diet-induced obesity, insulin resistance, type 2 diabetes, and fatty liver disease. These mice have altered cellular and systemic lipid transport and composition, leading to enhanced insulin receptor signaling, enhanced muscle AMP-activated kinase (AMP-K) activity, and dramatically reduced liver stearoyl-CoA desaturase-1 (SCD-1) activity underlying their phenotype. Taken together with the previously reported strong protection against atherosclerosis, these results demonstrate that adipocyte/macrophage FABPs have a robust impact on multiple components of metabolic syndrome, integrating metabolic and inflammatory responses in mice and constituting a powerful target for the treatment of these diseases.

Published 1 August 2005 in Cell Metab, 1(2): 107-19.
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Diabetes Research Today Archive:

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Diabetes Books

The New Glucose Revolution for Diabetes: The Definitive Guide to Managing Diabetes and Prediabetes Using the Glycemic Index (Marlowe Diabetes Library)

The New Glucose Revolution for Diabetes: The Definitive Guide to Managing Diabetes and Prediabetes Using the Glycemic Index (Marlowe Diabetes Library)