Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice - PubMed (original) (raw)

Diet-induced alterations in intestinal and extrahepatic lipid metabolism in liver fatty acid binding protein knockout mice

Elizabeth P Newberry et al. Mol Cell Biochem. 2009 Jun.

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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Figures

Fig. 1

Fig. 1

Average weekly weight gain of C57BL/6 and _L-fabp_−/− mice on high-fat and high-cholesterol diets. Mice were started on the high cholesterol diets at 8 weeks of age, and on the high-fat diets at 10–12 weeks of age. Mice were weighed weekly and maintained on diet for 10–20 weeks. Weekly weight gain for each mouse was calculated from weight gain after 10–12 weeks on diet divided by number of weeks on diet. Data are expressed as average ± SE, with n of 7–18 mice per group. Black bars C57BL/6 mice; _gray bars L-fabp_−/− mice. Asterisks indicate P < 0.05 versus C57BL/6 mice fed with the same diet

Fig. 2

Fig. 2

Intestinal cholesterol absorption in chow and cholesterol-fed mice. Cholesterol absorption was examined in the same group of female mice (n = 4–5) fed with either a chow diet (studied at 8 weeks, immediately prior to start of cholesterol diet feeding) or after 8 weeks on the 1.25% cholesterol semi-synthetic diet. Black bars: C57BL/6 mice; gray bars: _L-fabp_−/− mice. Asterisks indicate P < 0.05 versus C57BL/6 mice fed with the same diet

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