Journal
AMERICAN JOURNAL OF PHYSIOLOGY-GASTROINTESTINAL AND LIVER PHYSIOLOGY
Volume 294, Issue 1, Pages G307-G314Publisher
AMER PHYSIOLOGICAL SOC
DOI: 10.1152/ajpgi.00377.2007
Keywords
diet-induced obesity; hepatic triglyceride; cholesterol metabolism; saturated fatty acid; polyunsaturated fatty acid
Categories
Funding
- NHLBI NIH HHS [R01 HL038180, HL-38180] Funding Source: Medline
- NIDDK NIH HHS [P30 DK056341, P60 DK-020579-30, P30 DK056341-08, P30 DK056341-07, DK-52574, P30 DK-56341, R01 DK056260] Funding Source: Medline
- NATIONAL HEART, LUNG, AND BLOOD INSTITUTE [R37HL038180, R01HL038180] Funding Source: NIH RePORTER
- NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES [P30DK052574, R01DK056260, P30DK056341, P60DK020579] Funding Source: NIH RePORTER
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Liver fatty acid (FA)binding protein (L-Fabp), a cytoplasmic protein expressed in liver and small intestine, regulates FA trafficking in vitro and plays an important role in diet-induced obesity. We observed that L-Fabp(-/-) mice are protected against Western diet-induced obesity and hepatic steatosis. These findings are in conflict, however, with another report of exaggerated obesity and increased hepatic steatosis in female L-Fabp(-/-) mice fed a cholesterol-supplemented diet. To resolve this apparent paradox, we fed female L-Fabp(-/-) mice two different cholesterol-supplemented low-fat diets and discovered (on both diets) lower body weight in L-Fabp(-/-) mice than in congenic wild-type C57BL/6J controls and similar or reduced hepatic triglyceride content. We extended these comparisons to mice fed low-cholesterol, high-fat diets. Female L-Fabp(-/-) mice fed a high-saturated fat (SF) diet were dramatically protected against obesity and hepatic steatosis, whereas weight gain and hepatic lipid content were indistinguishable between mice fed a high-polyunsaturated FA (PUFA) diet and control mice. These findings demonstrate that L-Fabp functions as a metabolic sensor with a distinct hierarchy of FA sensitivity. We further conclude that cholesterol supplementation does not induce an obesity phenotype in L-Fabp(-/-) mice, nor does it play a significant role in the protection against Western diet-induced obesity in this background.
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