Project description:Background Small intestine and liver greatly contribute to whole body lipid, cholesterol and phospholipid metabolism but to which extent cholesterol and phospholipid handling in these tissues is affected by high fat Western-style obesogenic diets remains to be defined. We therefore quantified cholesterol and phospholipid concentrations in intestine and liver and determined fecal neutral sterol and bile acid excretion in C57Bl/6N mice fed for 12 weeks either a cholesterol-free high carbohydrate control diet or a high fat diet containing 0.03 % (w/w) cholesterol. To identify underlying mechanisms of dietary adaptation in intestine and liver, changes in gene expression were assessed by microarray and qPCR profiling, respectively. Results Animals on high fat diet showed increased plasma cholesterol levels, associated with the higher dietary cholesterol supply, yet, significantly reduced cholesterol levels were found in intestine and liver. Transcript profiling revealed evidence that expression of numerous genes involved in cholesterol synthesis and uptake via LDL, but also in phospholipid metabolism, underwent compensatory regulations in both tissues. Alterations in glycerophospholipid metabolism were confirmed at the metabolite level by phospolipid profiling via mass spectrometry. Conclusions Our findings suggest that intestine and liver react to a high dietary fat intake by an activation of de novo cholesterol synthesis and other cholesterol-saving mechanisms, as well as with major changes in phospholipid metabolism, to accommodate to the fat load. The proximal part of the intestine of mice fed either a control or a high fat diet were analyzed. 5 replicates each.

2011-08-31 | E-GEOD-29748 | biostudies-arrayexpress

Feedback regulation of cholesterol metabolism by LeXis, a lipid-responsive non-coding RNA

Project description:Abstract: The LXR and SREBP transcription factors are key regulators of cellular and systemic cholesterol homeostasis. The molecular mechanisms that integrate these pathways are incompletely understood. Here we show that ligand activation of LXRs in liver not only promotes cholesterol efflux, but also simultaneously inhibits cholesterol biosynthesis. We further identify the long non-coding RNA LeXis as an unexpected mediator of this effect. LeXis is robustly induced in mouse liver in response to western diet feeding or pharmacologic LXR activation. Expression of LeXis in liver inhibits cholesterol biosynthesis and lowers plasma cholesterol levels. Reciprocally, knockdown of LeXis increases hepatic cholesterol content and raises plasma cholesterol levels. LeXis interacts with the heterogeneous nuclear ribonucleoprotein Raly and regulates its binding to cholesterol biosynthetic gene promoters. These studies outline a regulatory role for a non-coding RNA in lipid metabolism and advance our understanding of the mechanisms orchestrating systemic sterol homeostasis. Global RNA expression from primary hepatocytes treated with or without GW3965 were compared by RNA-Seq.

2016-02-10 | E-GEOD-77793 | biostudies-arrayexpress

C57Bl/6N Mice on High Fat Diet Display Reduced Intestinal and Hepatic Cholesterol Levels despite a Plasma Hypercholesterolemia

2011-09-01 | GSE29748 | GEO

SEC24A deficiency lowers plasma cholesterol through reduced PCSK9 secretion.

Project description: Not available

| S-EPMC3622177 | biostudies-literature

Corn Oil Lowers Plasma Cholesterol Compared with Coconut Oil in Adults with Above-Desirable Levels of Cholesterol in a Randomized Crossover Trial.

Project description: Not available

| S-EPMC6168703 | biostudies-literature