| 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
(Affiliation: Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.)
|
| 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 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)
|
