Transcriptional regulation of cholesterol and bile acid metabolism after dietary soyabean meal treatment in Atlantic salmon (Salmo salar L.)

Inclusion of plant protein sources such as soyabean meal (SBM) in aquafeeds is associated with decreased lipid digestibility, reduced bile acid levels and hypocholesterolaemia. The mechanism for these metabolic abnormalities is unknown. The present study aimed at gaining further insight into how cholesterol and bile acid metabolism is modulated by SBM feeding by quantifying a number of mRNA species corresponding to key proteins involved in cholesterol and bile acid metabolism using quantitative real-time PCR. A 21 d feeding trial with sequential sampling at ten time points following initiation of 20 % SBM exposure was conducted on Atlantic salmon. A histological evaluation confirmed distal intestinal enteritis after 5 d of dietary exposure to the SBM, whereas diminished glycogen/lipid deposition was the only relevant finding observed in the liver. SBM inclusion resulted in reduced body pools of cholesterol and bile acids. Hepatic gene expression profiles revealed up-regulation of genes encoding rate-limiting enzymes in cholesterol (3-hydroxy-3-methyl-glutaryl-CoA reductase; HMGCR) and bile acid (cytochrome P4507A1 (CYP7A1)) biosynthesis, as well as up-regulation of their associated transcription factors (sterol regulatory element binding proteins 1 and 2, liver X receptor, farnesoid X receptor and PPAR isoforms). Hepatic gene expressions of cholesterol (ATP binding cassette G5 (ABCG5)) and bile acid (ATP binding cassette B11 (ABCB11)) transporters were, by and large, not influenced by the SBM, but distal intestinal expression patterns of ABCG5 and apical Na-dependent bile acid transporter indicated impaired cholesterol and bile acid reabsorption. In conclusion, hepatic gene expression profiles indicated that the capacity for cholesterol and bile acid synthesis was up-regulated, whereas the indicated impaired cholesterol and bile acid reabsorption probably occurred as a direct result of distal intestinal inflammation.

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The influence of rosuvastatin on the gastrointestinal microbiota and host gene expression profiles

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00149.2016 ◽

2017 ◽

Vol 312 (5) ◽

pp. G488-G497 ◽

Cited By ~ 17

Author(s):

J. A. Nolan ◽

P. Skuse ◽

K. Govindarajan ◽

E. Patterson ◽

N. Konstantinidou ◽

...

Keyword(s):

Gene Expression ◽

Community Structure ◽

Bile Acid ◽

Microbial Community ◽

Gut Microbiota ◽

Acid Metabolism ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Bile Acid Metabolism ◽

Gastrointestinal Microbiota

Statins are the most widely prescribed medications worldwide for the treatment of hypercholesterolemia. They inhibit the activity of 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMG-R), an enzyme involved in cholesterol synthesis in higher organisms and in isoprenoid biosynthesis in some bacteria. We hypothesized that statins may influence the microbial community in the gut through either direct inhibition or indirect mechanisms involving alterations to host responses. We therefore examined the impact of rosuvastatin (RSV) on the community structure of the murine gastrointestinal microbiota. RSV was orally administered to mice and the effects on the gut microbiota, host bile acid profiles, and markers of inflammation were analyzed. RSV significantly influenced the microbial community in both the cecum and feces, causing a significant decrease in α-diversity in the cecum and resulting in a reduction of several physiologically relevant bacterial groups. RSV treatment of mice significantly affected bile acid metabolism and impacted expression of inflammatory markers known to influence microbial community structure (including RegIIIγ and Camp) in the gut. This study suggests that a commonly used statin (RSV) leads to an altered gut microbial composition in normal mice with attendant impacts on local gene expression profiles, a finding that should prompt further studies to investigate the implications of statins for gut microbiota stability and health in humans. NEW & NOTEWORTHY This work demonstrates that rosuvastatin administration in mice affects the gastrointestinal microbiota, influences bile acid metabolism, and alters transcription of genes encoding factors involved in gut homeostasis and immunity in the gastrointestinal tract.

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Mo1530 Ligand Dependent Hepatic Gene Expression Profiles of Nuclear Receptors Car and PXR

Gastroenterology ◽

10.1016/s0016-5085(12)63830-x ◽

2012 ◽

Vol 142 (5) ◽

pp. S-988

Author(s):

Satoru Kakizaki ◽

Hiroki Tojima ◽

Yuichi Yamazaki ◽

Daichi Takizawa ◽

Norio Horiguchi ◽

...

Keyword(s):

Gene Expression ◽

Nuclear Receptors ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Hepatic Gene Expression

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Isolation stress for 30 days alters hepatic gene expression profiles, especially with reference to lipid metabolism in mice

Physiological Genomics ◽

10.1152/physiolgenomics.90358.2008 ◽

2009 ◽

Vol 37 (2) ◽

pp. 79-87 ◽

Cited By ~ 12

Author(s):

Keiko Motoyama ◽

Yuji Nakai ◽

Tomoya Miyashita ◽

Yuichiro Fukui ◽

Maki Morita ◽

...

Keyword(s):

Gene Expression ◽

Lipid Metabolism ◽

Dna Microarray ◽

Social Stress ◽

Secretory Pathway ◽

Expression Profiles ◽

Regulatory Element ◽

Gene Expression Profiles ◽

Hepatic Gene Expression ◽

Isolation Stress

To elucidate the physiological responses to a social stressor, we exposed mice to an isolation stress and analyzed their hepatic gene expression profiles using a DNA microarray. Male BALB/c mice were exposed to isolation stress for 30 days, and then hepatic RNA was sampled and subjected to DNA microarray analysis. The isolation stress altered the expression of 420 genes (after considering the false discovery rate). Gene Ontology analysis of these differentially expressed genes indicated that the stress remarkably downregulated the lipid metabolism-related pathway through peroxisome proliferator-activated receptor-α, while the lipid biosynthesis pathway controlled by sterol regulatory element binding factor 1, Golgi vesicle transport, and secretory pathway-related genes were significantly upregulated. These results suggest that isolation for 30 days with a mild and consecutive social stress regulates the systems for lipid metabolism and also causes endoplasmic reticulum stress in mouse liver.

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