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

Elizabeth P. Newberry, Susan M. Kennedy, Yan Xie, Britni T. Sternard, Jianyang Luo, Nicholas O. Davidson

Research output: Contribution to journalArticlepeer-review

57 Scopus citations

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.

Original languageEnglish
Pages (from-to)G307-G314
JournalAmerican Journal of Physiology - Gastrointestinal and Liver Physiology
Volume294
Issue number1
DOIs
StatePublished - 2007

Keywords

  • Cholesterol metabolism
  • Diet-induced obesity
  • Hepatic triglyceride
  • Polyunsaturated fatty acid
  • Saturated fatty acid

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