Diet-induced obesity and hepatic steatosis in L-Fabp / mice is abrogated with SF, but not PUFA, feeding and attenuated after cholesterol supplementation.
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.
Newberry
Elizabeth P
EP
Department of Medicine, Washington University School of Medicine, St. Louis, MO 63110, USA.
Kennedy
Susan M
SM
Xie
Yan
Y
Sternard
Britni T
BT
Luo
Jianyang
J
Davidson
Nicholas O
NO
D000818:Animals; D001835:Body Weight; D002791:Cholesterol, Dietary / Q000008:administration & dosage* / Q000378:metabolism; D004195:Disease Models, Animal; D050556:Fatty Acid-Binding Proteins / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D005227:Fatty Acids / Q000008:administration & dosage* / Q000378:metabolism; D005231:Fatty Acids, Unsaturated / Q000008:administration & dosage* / Q000378:metabolism; D005234:Fatty Liver / Q000209:etiology / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D005260:Female; D050356:Lipid Metabolism / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000150:complications / Q000235:genetics / Q000378:metabolism / Q000517:prevention & control*; D012333:RNA, Messenger / Q000378:metabolism; D013997:Time Factors; D014280:Triglycerides / Q000378:metabolism
D002791:Cholesterol, Dietary; C493320:Fabp1 protein, mouse; C082667:Fabp5 protein, mouse; D050556:Fatty Acid-Binding Proteins; D005227:Fatty Acids; D005231:Fatty Acids, Unsaturated; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D014280:Triglycerides