Abstract
Liver fatty acid binding protein (L-FABP) is highly expressed in both enterocytes and hepatocytes and binds multiple ligands, including saturated (SFA), unsaturated fatty acids (PUFA), and cholesterol. L-fabp −/− mice were protected against obesity and hepatic steatosis on a high saturated fat (SF), high cholesterol “Western” diet and manifested a similar phenotype when fed with a high SF, low cholesterol diet. There were no significant differences in fecal fat content or food consumption between the genotypes, and fatty acid (FA) oxidation was reduced, rather than increased, in SF-fed L-fabp −/− mice as evidenced by decreased heat production and serum ketones. In contrast to mice fed with a SF diet, L-fabp −/− mice fed with a high PUFA diet were not protected against obesity and hepatic steatosis. These observations together suggest that L-fabp −/− mice exhibit a specific defect in the metabolism of SFA, possibly reflecting altered kinetics of FA utilization. In support of this possibility, microarray analysis of muscle from Western diet-fed mice revealed alterations in genes regulating glucose uptake and FA synthesis. In addition, intestinal cholesterol absorption was decreased in L-fabp −/− mice. On the other hand, and in striking contrast to other reports, female L-fabp −/− mice fed with low fat, high cholesterol diets gained slightly less weight than control mice, with minor reductions in hepatic triglyceride content. Together these data indicate a role for L-FABP in intestinal trafficking of both SFA and cholesterol.
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Acknowledgments
This work was supported by grants from the NIH to NOD (HL-38180, DK-56260, and DK-52574, particularly the Genomics and Microarray Core). The authors acknowledge Trey Coleman and the Clinical Nutrition Research Unit for assistance with the energy consumption studies (NIDDK P30 DK-56341). The authors acknowledge the Diabetes Research Training Center Immunoassay Core for help with serum analysis (P60 DK-020579-30). The authors are grateful to Valerie Blanc, Kim Delaney, Britni Sternard, and Susie Stanley for useful discussions throughout the course of these studies.
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Newberry, E.P., Kennedy, S.M., Xie, Y. et al. Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice. Mol Cell Biochem 326, 79–86 (2009). https://doi.org/10.1007/s11010-008-0002-4
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DOI: https://doi.org/10.1007/s11010-008-0002-4