Gene expression analysis of a human enterocyte cell line reveals downregulation of cholesterol biosynthesis in response to short‐chain fatty acids

Álvaro, Adriana; Solà, Rosa; Rosales, Roser; Ribalta, Josep; Anguera, Anna; Masana, Luís; Vallvé, Joan-Carles

doi:10.1002/iub.110

Cited by 105 publications

(73 citation statements)

References 33 publications

(17 reference statements)

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“…Although the liver is clearly a major site for lipid metabolism in the body, the intestine is also an important contributor and both tissues play a role in the overall lipid balance in the body [40]. Given the rising incidence of obesity and insulin resistance, treatments that target lipid metabolism in the intestine and inhibit intestinal fat absorption are increasingly important.…”

Section: Discussionmentioning

confidence: 99%

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Chen¹,

Reimer²

2009

Nutrition

142

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Objective-A growing body of evidence supports an antiobesity effect of dairy products; however, the mechanisms remain unclear. The objective of this study was to explore possible intestinal mechanisms by which dairy delivers an antiobesity effect. The human intestinal cell line, NCI-H716, was used to test the hypothesis that branched-chain amino acids and dairy proteins regulate satiety hormone secretion and modulate genes involved in fatty acid and cholesterol metabolism.Methods-In dose-response (0.5%, 1.0%, 2.0%, and 3.0%) studies, the effect of leucine, isoleucine, valine, skim milk, casein, and whey on glucagon-like peptide-1 release and the expression of selected genes were tested.Results-Leucine, isoleucine, skim milk, and casein stimulated glucagon-like peptide-1 release (P < 0.05). Isoleucine and whey downregulated the expression of intestinal-type fatty acid binding protein (i-FABP), fatty acid transport protein 4 (FATP4), Niemann-Pick C-1-like-1 protein (NPC1L1), acetyl-coenzyme A carboxylase (ACC), fatty acid synthase (FAS), sterol regulatory element-binding protein-2 (SREBP-2), and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR; P < 0.05). Leucine and valine downregulated the expression of NPC1L1, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Casein downregulated the expression of i-FABP, FATP4, ACC, FAS, SREBP-2, and HMGCR (P < 0.05). Skim milk downregulated the expression of ACC, FAS, and SREBP-2, but not i-FABP, FATP4, and NPC1L1.Conclusion-This work suggests that the antiobesity effect of dairy may be mediated, at least in part, by integration of events that promote glucagon-like peptide-1 secretion and inhibit expression of genes involved in intestinal fatty acid and cholesterol absorption and synthesis.

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Section: Discussionmentioning

confidence: 99%

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Chen¹,

Reimer²

2009

Nutrition

142

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“…Hybridization of microarrays and data acquisition was carried out in the London Regional Genomics Facility (University of Western Ontario, London, Canada) using the 24K Affymetrix GeneChip Bovine Genome Arrays (Affymetrix, Santa Clara, CA). A complete description of the microarray hybridization protocol can be found in the Supplemental Material 1 1 and the 1 The online version of this article contains supplemental material. Gene Expression Omnibus repository (GSE17849).…”

Section: Microarray Pathway and Network Analysismentioning

confidence: 99%

Rumen epithelial adaptation to high-grain diets involves the coordinated regulation of genes involved in cholesterol homeostasis

Steele

Vandervoort

AlZahal

et al. 2011

Physiological Genomics

106

108

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BW. Rumen epithelial adaptation to high-grain diets involves the coordinated regulation of genes involved in cholesterol homeostasis. Physiol Genomics 43: 308 -316, 2011. First published January 18, 2011 doi:10.1152/physiolgenomics.00117.2010.-The molecular mechanisms underlying rumen epithelial adaption to highgrain (HG) diets are unknown. To gain insight into the metabolic mechanisms governing epithelial adaptation, mature nonlactating dairy cattle (n ϭ 4) were transitioned from a high-forage diet (HF, 0% grain) to an HG diet (65% grain). After the cattle were fed the HG diet for 3 wk, they returned to the original HF diet, which they were fed for an additional 3 wk. Continuous ruminal pH, ruminal short chain fatty acids, and plasma ␤-hydroxybutyrate were measured on a weekly basis, and rumen papillae were biopsied from the ventral sac to assess alterations in mRNA expression profiles. The subacute form of ruminal acidosis was diagnosed during the first week of the HG period (4.6 Ϯ 1.6 h/day ϽpH 5.6), but not during weeks 2 and 3, thereby indicating ruminal adaption to the HG diet. Changes in the mRNA expression profile of rumen papillae were initially examined using Bovine Affymetrix microarrays; a total of 521 differentially expressed genes (false discovery rate P Ͻ 0.08) were uncovered from the first to third week of the HG period. Ingenuity Pathway Analysis of microarray results revealed that enzymes involved in cholesterol synthesis were coordinately downregulated from the first to third week of the HG period. In addition, the LXR/RXR activation pathway was significant and included several genes involved in intracellular cholesterol homeostasis. The differential expression signature of eight genes representing the key regulatory points of cholesterol homeostasis was confirmed by quantitative real-time PCR. Based upon our pathway and network results we propose a model to explain cellular events during rumen epithelial adaptation to HG diets and thus provide molecular targets that may be useful in the treatment and prevention of ruminal acidosis. ruminal acidosis; rumen epithelium; acidosis; gene expression IN INTENSIVE RUMINANT LIVESTOCK systems, rapidly fermentable (high grain) diets are commonly utilized to increase energy intake. When ruminants are fed high-grain (HG) diets, short chain fatty acid (SCFA) production can exceed absorption and ruminal pH can be depressed causing ruminal acidosis (8,62,66). Subacute ruminal acidosis (SARA), which is diagnosed when ruminal pH falls Ͻ5.6 for more than 3 h per day, is common in commercial dairy cows (2, 26). It has been estimated that 20% of all commercial dairy cattle in North America suffer from SARA (64) at a cost of $1.12 US per cow per day (78). SARA is associated with extensive alterations in rumen microflora populations and has a wide variety of clinical manifestations including depressed feed intake and milk production, liver abscesses, diarrhea, and inflammation (70).The rumen is the first organ to face the insult of graininduced SARA. Therefore, SAR...

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“…by inhibition of proinflammatory cytokine-induced NF B activation and absorption of sodium and water [2][3][4]. In addition, SCFAs and especially butyrate are known to influence intestinal specific gene expression, thereby influencing immune responses and oxidative and metabolic stress [5][6][7][8][9]. The composition of SCFAs in the intestine is determined by the composition of the microbiota, which in its turn is influenced by the diet.…”

Section: Introductionmentioning

confidence: 99%

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

Paassen¹,

Vincent²,

Puiman³

et al. 2009

Gastroenterology

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Gene expression analysis of a human enterocyte cell line reveals downregulation of cholesterol biosynthesis in response to short‐chain fatty acids

Cited by 105 publications

References 33 publications

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Dairy protein and leucine alter GLP-1 release and mRNA of genes involved in intestinal lipid metabolism in vitro

Rumen epithelial adaptation to high-grain diets involves the coordinated regulation of genes involved in cholesterol homeostasis

218 The Regulation of the Intestinal Mucin MUC2 Expression By Short Chain Fatty Acids: Implications for Epithelial Protection

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