Journal of Biological Chemistry
Volume 278, Issue 6, 7 February 2003, Pages 3992-3999
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METABOLISM AND BIOENERGETICS
Opposite Effects of Background Genotype on Muscle and Liver Insulin Sensitivity of Lipoatrophic Mice: ROLE OF TRIGLYCERIDE CLEARANCE*

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The metabolic phenotype of the A-ZIP/F-1 (AZIP) lipoatrophic mouse is different depending on its genetic background. On both the FVB/N (FVB) and C57BL/6J (B6) backgrounds, AZIP mice have a similarly severe lack of white adipose tissue and comparably increased insulin levels and triglyceride secretion rates. However, on the B6 background, the AZIP mice have less hyperglycemia, lower circulating triglyceride and fatty acid levels, and lower mortality. AZIP characteristics that are more severe on the B6 background include increased liver size and liver triglyceride content. A unifying hypothesis is that the B6 strain has higher triglyceride clearance into the liver, with lower triglyceride levels elsewhere. This may account for the observation that the B6 AZIP mice have less insulin-resistant muscles and more insulin-resistant livers, than do the FVB AZIP mice. B6 wild type, as well as B6 AZIP, mice have increased triglyceride clearance relative to FVB, which may be explained in part by higher serum lipase levels and liver CD36/fatty acid translocase mRNA levels. Thus, it is likely that increased triglyceride clearance in B6, as compared with FVB, mice contributes to the strain differences in insulin resistance and lipid metabolism.

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Published, JBC Papers in Press, November 26, 2002, DOI 10.1074/jbc.M207665200

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The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

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Present address: 3 Dept. of Internal Medicine, 1 Faculty of Medicine, Charles University, Prague, Czech Republic.

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Current address: Via Adda 17, 20010 Villastanza, Milano, Italy.