Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0020473 (hyperlipidemia)
 15,891 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Postprandial dyslipidemia is a common feature of insulin-resistant states and contributes to increased cardiovascular disease risk. Recently, bile acids have been recognized beyond their emulsification properties as important signaling molecules that promote energy expenditure, improve insulin sensitivity, and lower fasting lipemia. Although bile acid receptors have become novel pharmaceutical targets, their effects on postprandial lipid metabolism remain unclear. Here, we investigated the potential role of bile acids in regulation of postprandial chylomicron production and triglyceride excursion. Healthy C57BL/6 mice were given an intraduodenal infusion of taurocholic acid (TA) under fat-loaded conditions, and circulating lipids were measured. Targeting of bile acid receptors was achieved with GW4064, a synthetic agonist to the farnesoid X receptor (FXR), and deoxycholic acid (DCA), an activator of the Takeda G-protein-coupled receptor 5. TA, GW4064, and DCA treatments all lowered postprandial lipemia. FXR agonism also reduced intestinal triglyceride content and activity of microsomal triglyceride transfer protein, involved in chylomicron assembly. Importantly, TA (but not DCA) effects were largely lost in FXR knockout mice. These bile acid effects are reminiscent of the antidiabetic hormone glucagon-like peptide-1 (GLP-1). Although the GLP-1 receptor agonist exendin-4 retained its ability to acutely lower postprandial lipemia during bile acid sequestration and FXR deficiency, it did raise hepatic expression of the rate-limiting enzyme for bile acid synthesis. Bile acid signaling may be an important mechanism of controlling dietary lipid absorption, and bile acid receptors may constitute novel targets for the treatment of postprandial dyslipidemia.NEW & NOTEWORTHY We present new data suggesting potentially important roles for bile acids in regulation of postprandial lipid metabolism. Specific bile acid species, particularly secondary bile acids, were found to markedly inhibit absorption of dietary lipid and reduce postprandial triglyceride excursion. These effects appear to be mediated via bile acid receptors, farnesoid X receptor (FXR) and Takeda G protein-coupled receptor 5 (TGR5). Importantly, bile acid signaling may trigger glucagon-like peptide-1 (GLP-1) secretion, which may in turn mediate the marked inhibitory effects on dietary fat absorption.
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PMID:Bile acid treatment and FXR agonism lower postprandial lipemia in mice. 3200 2

Berberine compounds (BC), consisting of berberine (BBR), oryzanol and vitamin B6, have been used to treat diabetes and hyperlipidemia in recent years, but the potential mechanisms under the effects have not been well determined. In this study, we evaluated the effect of BC in db/db mice, and found that BC treatment reversed the increased levels of fasting glucose and hemoglobin A1c in db/db mice, which was superior to BBR treatment. Fecal 16S rRNA gene sequencing indicated that BC increased relative abundance of microbiomes Bacteroidaceae and Clostridiaceae, which may promote conversion of primary bile acid cholic acid (CA) into secondary bile acid deoxycholic acid (DCA). Gas chromatography/mass spectrometry (GC/MS)-based metabolomics revealed that BC treatment increased fecal DCA level. Since DCA processes the potential to activate bile acid receptor-takeda G protein-coupled receptor 5 (TGR5) and induce glucagon-like peptide (GLP) secretion, we detected TGR5 expression, and found that BC-treatment significantly increased the colonic TGR5 and serum GLP-1/-2 levels in db/db mice. Modulation of TGR5-GLP pathway may also affect metabolomic profiles of serum and liver, and BC treatment showed effects on restoring the altered carbohydrate, lipid, amino acid and nucleotide metabolism. Our study suggested that BC improved hyperglycemia, the effect might attribute to the increased microbiome mediated DCA production, which up-regulated colonic TGR5 expression and GLP secretion, and improved glucose, lipid and energy metabolism in db/db mice.
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PMID:Berberine compounds improves hyperglycemia via microbiome mediated colonic TGR5-GLP pathway in db/db mice. 3325 41