Diet-induced obesity and hepatic steatosis in L-Fabp / mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation.

Abstract

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.

• Authors: Elizabeth P Newberry, Susan M Kennedy, Yan Xie, Britni T Sternard, Jianyang Luo, Nicholas O Davidson
• Journal: American journal of physiology. Gastrointestinal and liver physiology (Am J Physiol Gastrointest Liver Physiol) Vol. 294 Issue 1 Pg. G307-14 (Jan 2008) ISSN: 0193-1857 [Print] United States
• PMID: 18032478 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Cholesterol, Dietary
• Fabp1 protein, mouse
• Fabp5 protein, mouse
• Fatty Acid-Binding Proteins
• Fatty Acids
• Fatty Acids, Unsaturated
• Neoplasm Proteins
• RNA, Messenger
• Triglycerides

Topics

• Animals
• Body Weight
• Cholesterol, Dietary (administration & dosage, metabolism)
• Disease Models, Animal
• Fatty Acid-Binding Proteins (deficiency, genetics, metabolism)
• Fatty Acids (administration & dosage, metabolism)
• Fatty Acids, Unsaturated (administration & dosage, metabolism)
• Fatty Liver (etiology, genetics, metabolism, prevention & control)
• Female
• Lipid Metabolism (genetics)
• Liver (metabolism)
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Neoplasm Proteins (genetics, metabolism)
• Obesity (chemically induced, complications, genetics, metabolism, prevention & control)
• RNA, Messenger (metabolism)
• Time Factors
• Triglycerides (metabolism)