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Am J Physiol Endocrinol Metab (November 22, 2005). doi:10.1152/ajpendo.00465.2005
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Submitted on September 23, 2005
Accepted on November 17, 2005

Lipid Metabolism and Adipokine Levels in Fatty Acid Binding Protein Null and Transgenic Mice

Ann V Hertzel1, Lisa A Smith1, Anders H Berg2, Gary W Cline3, Gerald I Shulman3, Philipp E Scherer2, and David A Bernlohr1*

1 Department of Biochemistry, Molecular Biology and Biophysics, University of Minnesota, Minneapolis, MN, USA
2 Department of Cell Biology and Medicine, Albert Einstein College of Medicine, Bronx, NY, USA
3 Department of Internal Medicine, Howard Hughes Medical Institute, Yale University, New Haven, CT, USA

* To whom correspondence should be addressed. E-mail: bernl001{at}umn.edu.

Fatty acid binding proteins (FABPs) facilitate the diffusion of fatty acids within cellular cytoplasm. When compared to C57Bl/6J mice maintained on a high-fat diet, adipose-FABP null mice exhibit increased fat mass, decreased lipolysis, increased muscle glucose oxidation and attenuated insulin resistance while over expression of E-FABP in adipose tissue results in decreased fat mass, increased lipolysis and potentiated insulin resistance. To identify the mechanisms that underlie these processes, real-time PCR analyses indicate that the expression of hormone sensitive lipase is reduced while perilipin A is increased in A-FABP/aP2 null mice relative to E-FABP over expressing mice. In contrast, de novo lipogenesis and expression of genes encoding LPL, CD36, ACSL5 and DGAT are increased in A-FABP/aP2 null mice relative to E-FABP transgenic animals. Consistent with an increase in de novo lipogenesis, there was an increase in adipose C16:0 and C16:1 acyl CoA pools. There were no changes in serum free fatty acids between genotypes. Serum levels of resistin were decreased in the E-FABP transgenic mice whereas serum and tissue adiponectin were increased in A-FABP/aP2 null mice and decreased in E-FABP transgenic animals; leptin expression was unaffected. These results suggest that the balance between lipolysis and lipogenesis in adipocytes is remodeled in the FABP null and transgenic mice and is accompanied by the reprogramming of adipokine expression in fat cells and overall changes in plasma adipokines.




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