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Publication
Dietary cholesterol reverses resistance to diet-induced weight gain in mice
lacking Niemann-Pick C1-Like 1.
Authors Jia L, Ma Y, Liu G, Yu L
Submitted By Submitted Externally on 8/4/2017
Status Published
Journal Journal of lipid research
Year 2010
Date Published
Volume : Pages 51 : 3024 - 33
PubMed Reference 20601625
Abstract Niemann-Pick C1-Like 1 (NPC1L1) mediates intestinal cholesterol absorption.
NPC1L1 knockout (L1-KO) mice were recently shown to be resistant to high-fat
diet (HFD)-induced obesity in one study, which was contrary to several other
studies. Careful comparison of dietary compositions in these studies implies a
potential role of dietary cholesterol in regulating weight gain. To examine this
potential, wild-type (WT) and L1-KO mice were fed one of three sets of diets for
various durations: (1) a HFD without added cholesterol for 5 weeks; (2) a
high-carbohydrate diet with or without added cholesterol for 5 weeks; or (3) a
synthetic HFD with or without added cholesterol for 18 weeks. We found that
L1-KO mice were protected against diet-induced weight gain only on a diet
without added cholesterol but not on a diet containing 0.16% or 0.2% (w/w)
cholesterol, an amount similar to a typical Western diet, regardless of the
major energy source of the diet. Food intake and intestinal fat absorption were
similar between the two genotypes. Intestinal cholesterol absorption was
blocked, and fecal cholesterol excretion increased in L1-KO mice. Under all
diets, L1-KO mice were protected from hepatosteatosis. In conclusion, increasing
dietary cholesterol restores diet-induced weight gain in mice deficient in
NPC1L1-dependent cholesterol absorption.




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