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Liver fatty acid binding protein gene ablation enhances age-dependent weight gain in male mice

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Abstract

Although studies performed in vitro and with transfected cells in culture suggest a role for liver fatty acid binding protein (L-FABP) in regulating fatty acid oxidation and fat deposition, the physiological significance of this possibility is not completely clear. To begin to address this question, the effect of L-FABP gene ablation on phenotype of standard rodent chow-fed male mice was examined with increasing age up to 18 months. While young (2–3 months old) L-FABP null mice displayed no visually obvious phenotype, with increasing age >9 months the L-FABP null mice were visibly larger, exhibiting increased body weight due to increased fat and lean tissue mass. Liver lipid concentrations were unaffected by L-FABP gene ablation with the exception of triacylglycerol, which was decreased by 74% in the livers of 3-month-old mice. Likewise, serum lipid levels were not altered in L-FABP null mice with the exception of triacylglycerol, which was increased in the serum of 18-month-old mice. Increased body weight, fat tissue mass, and lean tissue mass in 18-month-old L-FABP null mice were accompanied by increased hepatic levels of low-density lipoprotein (LDL) receptor, peroxisome proliferator-activated receptor (PPAR) α, and PPARα-regulated proteins such as fatty acid transport protein (FATP), fatty acid translocase (FAT/CD36), carnitine palmitoyl transferase I (CPT I), and lipoprotein lipase (LPL). A key enzyme in cholesterol biosynthesis, 3-hydroxy-3-methylglutaryl Coenzyme A (HMG-CoA) reductase, was down-regulated in L-FABP null mice. These findings were consistent with a proposed role for L-FABP as an important physiological regulator of PPARα.

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Acknowledgments

This work was supported in part by the United States Public Health Service National Institutes of Health grants DK41402 (FS and ABK), GM31651 (FS and ABK), and DK70965 (BPA).

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Authors and Affiliations

  1. Department of Physiology and Pharmacology, Texas A&M University, TVMC, College Station, TX, 77843-4466, USA

    Gregory G. Martin, Barbara P. Atshaves, Avery L. McIntosh & Friedhelm Schroeder

  2. Department of Pathobiology, Texas A&M University, TVMC, College Station, TX, 77843, USA

    H. Ross Payne, John T. Mackie & Ann B. Kier

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  1. Gregory G. Martin
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Martin, G.G., Atshaves, B.P., McIntosh, A.L. et al. Liver fatty acid binding protein gene ablation enhances age-dependent weight gain in male mice. Mol Cell Biochem 324, 101–115 (2009). https://doi.org/10.1007/s11010-008-9989-9

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