#microsomal triglyceride transfer protein

[rnomics]

Nutrients, Vol. 16, Pages 1929: Gut Dysbiosis Shaped by Cocoa Butter-Based Sucrose-Free HFD Leads to Steatohepatitis, and Insulin Resistance in Mice

Background: High-fat diets cause gut dysbiosis and promote triglyceride accumulation, obesity, gut permeability changes, inflammation, and insulin resistance. Both cocoa butter and fish oil are considered to be a part of healthy diets. However, their differential effects on gut microbiome perturbations in mice fed high concentrations of these fats, in the absence of sucrose, remains to be elucidated. The aim of the study was to test whether the sucrose-free cocoa butter-based high-fat diet (C-HFD) feeding in mice leads to gut dysbiosis that associates with a pathologic phenotype marked by hepatic steatosis, low-grade inflammation, perturbed glucose homeostasis, and insulin resistance, compared with control mice fed the fish oil based high-fat diet (F-HFD). Results: C57BL/6 mice (5–6 mice/group) were fed two types of high fat diets (C-HFD and F-HFD) for 24 weeks. No significant difference was found in the liver weight or total body weight between the two groups. The 16S #rRNA sequencing of gut bacterial samples displayed gut dysbiosis in C-HFD group, with differentially-altered microbial diversity or relative abundances. Bacteroidetes, Firmicutes, and Proteobacteria were highly abundant in C-HFD group, while the Verrucomicrobia, Saccharibacteria (TM7), Actinobacteria, and Tenericutes were more abundant in F-HFD group. Other taxa in C-HFD group included the Bacteroides, Odoribacter, Sutterella, Firmicutes bacterium (AF12), Anaeroplasma, Roseburia, and Parabacteroides distasonis. An increased Firmicutes/Bacteroidetes (F/B) ratio in C-HFD group, compared with F-HFD group, indicated the gut dysbiosis. These gut bacterial changes in C-HFD group had predicted associations with fatty liver disease and with lipogenic, inflammatory, glucose metabolic, and insulin signaling pathways. Consistent with its microbiome shift, the C-HFD group showed hepatic inflammation and steatosis, high fasting blood glucose, insulin resistance, increased hepatic de novo lipogenesis (Acetyl CoA carboxylases 1 (Acaca), Fatty acid synthase (Fasn), Stearoyl-CoA desaturase-1 (Scd1), Elongation of long-chain fatty acids family member 6 (Elovl6), Peroxisome proliferator-activated receptor-gamma (Pparg) and cholesterol synthesis (β-(hydroxy β-methylglutaryl-CoA reductase (Hmgcr). Non-significant differences were observed regarding fatty acid uptake (Cluster of differentiation 36 (CD36), Fatty acid binding protein-1 (Fabp1) and efflux (ATP-binding cassette G1 (Abcg1), Microsomal TG transfer protein (Mttp) in C-HFD group, compared with F-HFD group. The C-HFD group also displayed increased gene expression of inflammatory markers including Tumor necrosis factor alpha (Tnfa), C-C motif chemokine ligand 2 (Ccl2), and Interleukin-12 (Il12), as well as a tendency for liver fibrosis. Conclusion: These findings suggest that the sucrose-free C-HFD feeding in mice induces gut dysbiosis which associates with liver inflammation, steatosis, glucose intolerance and insulin resistance. https://www.mdpi.com/2072-6643/16/12/1929?utm_source=dlvr.it&utm_medium=tumblr

[pushingarrows]

Lomitapide - an inhibitor of the microsomal triglyceride transfer protein (MTTP) as a lipid lowering agent to reduce LDL cholesterol in patients with homozygous familial hypercholesterolemia (HoFH). It can be used in combination with other cholesterol lowering medications. MTTP is necessary for very low-density lipoprotein (VLDL) assembly and secretion in the liver.

[letssonalim-blog]

ReportsWeb.com published “Microsomal Triglyceride Transfer Protein Inhibitors Market” from its database. This report Strategic recommendations in key business segments based on the market estimations. This report Supply chain trends mapping the latest technological advancements.

[healthtimetaylor]

18β-glycyrrhetinic acid acts through hepatocyte nuclear factor 4 alpha to modulate lipid and carbohydrate metabolism.

PMID:  Pharmacol Res. 2020 Apr 28 ;157:104840. Epub 2020 Apr 28. PMID: 32353589 Abstract Title:  18β-Glycyrrhetinic acid acts through hepatocyte nuclear factor 4 alpha to modulate lipid and carbohydrate metabolism. Abstract:  Hepatocyte nuclear factor 4 alpha (HNF4α) regulates the expression of essential genes involved in very-low-density lipoprotein (VLDL) homeostasis and gluconeogenesis.　18β-glycyrrhetinic acid (GA) is an active ingredient of Glycyrrhiza uralensis an herbal medicine used for treating liver aliments. In this study, we established that GAfunctions as a partial antagonist of HNF4α through HNF4α-driven reporter luciferase assay and co-immunoprecipitation experiments with co-activator PGC1α. By virtual docking and site-directed mutagenesis analysis, we confirmed that serine 190 and arginine 235 of HNF4α are both essential for GA to exert its antagonistic action on HNF4α. Importantly, GA suppressed the expression of HNF4α target genes such as apolipoprotein B (ApoB), microsomal triglyceride transfer protein (MTP) and phospholipase AG12B (PLA2G12B) modulating hepatic VLDL secretion in mice fed on a high fat diet. In addition, GA also suppressed gluconeogenesis and ameliorated glucose intolerance via down-regulating the expression of HNF4α target genes glucose-6-phosphatase (G6pc) and phosphoenolpyruvate carboxykinase (Pepck). Furthermore, GA significantly lowered blood glucose and improved insulin resistance in db/db mice. In all, we established that GA acts as a partial HNF4α antagonist modulating lipid and carbohydrate metabolism.

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[eurekamag--com]

Inhibition of microsomal triglyceride transfer protein: Another mechanism for drug-induced steatosis in mice

http://dlvr.it/NDLHZQ

[sisiad]

RNA helicase DDX3 maintains lipid homeostasis through upregulation of the microsomal triglyceride transfer protein by interacting with HNF4 and SHP

http://dlvr.it/NCxTJh

[healthtimetaylor]

White tea plays important roles in ameliorating abnormal lipid metabolism in vitro.

PMID:  Biomed Pharmacother. 2020 Apr 22 ;127:110146. Epub 2020 Apr 22. PMID: 32334376 Abstract Title:  White tea and its active polyphenols lower cholesterol through reduction of very-low-density lipoprotein production and induction of LDLR expression. Abstract:  Emerging in vivo and vitro data suggest that white tea extract (WTE) is capable of favourably modulating metabolic syndrome, especially by ameliorating abnormal lipid metabolism. Microarray-based gene expression profiling was performed in HepG2 cells to analyze the effects of WTE from a systematic perspective. Gene Ontology and pathway analysis revealed that WTE significantly affected pathways related to lipid metabolism. WTE significantly downregulated apolipoprotein B (APOB) and microsomal triglyceride transfer protein (MTTP) expression and thereby reduced the production of very-low-density lipoprotein. In the meanwhile, WTE stimulated low-density lipoprotein-cholesterol (LDL-c) uptake through targeting low-density lipoprotein receptor (LDLR), as a consequence of the activation of sterol regulatory element-binding protein 2 (SREBP2) and peroxisome proliferator-activated receptorδ (PPARδ). Furthermore, WTE significantly downregulated triglycerides synthetic genes and reduced intracellular triglycerides accumulation. Besides, we demonstrated that the tea catechins epigallocatechin-3-gallate (EGCG) and epicatechin-3-gallate (ECG) are abundant in WTE and contribute to the regulation of cholesterol metabolism related genes, including LDLR, MTTP and APOB. Our findings suggest white tea plays important roles in ameliorating abnormal lipid metabolism in vitro.

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[healthtimetaylor]

Protective effect of patchouli alcohol against high-fat diet Induced hepatic steatosis.

PMID:  Front Pharmacol. 2019 ;10:1134. Epub 2019 Oct 1. PMID: 31632274 Abstract Title:  Protective Effect of Patchouli Alcohol Against High-Fat Diet Induced Hepatic Steatosis by Alleviating Endoplasmic Reticulum Stress and Regulating VLDL Metabolism in Rats. Abstract:  Nonalcoholic fatty liver disease (NAFLD) is currently the most common chronic hepatic disorder worldwide. The earliest stage of NAFLD is simple steatosis, which is characterized by the accumulation of triglycerides in hepatocytes. Inhibition of steatosis is a potential treatment for NAFLD. Patchouli alcohol (PA) is an active component of(Blanco) Benth. (Labiatae), which is a medicinal food in Asia countries and proved to possess hepatoprotective effect. This research aimed to investigate the effectiveness of PA against high fat diet (HFD)-induced hepatic steatosis in rats. In this study, male Sprague Dawley rats were fed a HFD for 4 weeks to induce NAFLD. Oral administration with PA significantly reduced pathological severity of steatosis in HFD-fed rats. It was associated with suppressing endoplasmic reticulum (ER) stress and regulating very low-density lipoprotein (VLDL) metabolism. Our data showed that PA treatment effectively attenuated ER stress by inhibiting the activation of protein kinase-like ER kinase (PERK), inositol-requiring transmembrane kinase/endoribonuclease 1 (IRE1), and activating transcription factor 6 (ATF6). Moreover, PA decreased hepatic VLDL uptake by suppressing very low-density lipoprotein receptor (VLDLR) expression. It also restored VLDL synthesis and export by increasing apolipoprotein B100 (apoB 100) secretion and microsomal triglyceride-transfer protein (MTP) activity. Taken together, PA exerted a protective effect on the treatment of NAFLD in HFD-fed rats and may be potential therapeutic agent acting on hepatic steatosis.

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[healthtimetaylor]

Barley sprout extracts reduce hepatic lipid accumulation in ethanol-fed mice by activating hepatic AMP-activated protein kinase.

PMID:  Food Res Int. 2017 11 ;101:209-217. Epub 2017 Sep 12. PMID: 28941686 Abstract Title:  Barley sprout extracts reduce hepatic lipid accumulation in ethanol-fed mice by activating hepatic AMP-activated protein kinase. Abstract:  Chronic alcohol consumption leads to hepatic lipid accumulation and alcoholic fatty liver disease. Previously, we demonstrated that barley sprout extract, which contains saponarin as an active compound, reduces hepatic steatosis. In this study, we investigated the effect of barley sprout extracts (BSE) on hepatic lipid accumulation in a mouse model of alcoholic fatty liver disease. Seven-week-old C57BL/6 mice were fed an alcohol-containing diet (5% ethanol) and a low or high dose of BSE (100 or 200mg/kg body weight, respectively) for 10days. The high dose of BSE significantly decreased hepatic lipid accumulation compared with the ethanol-only control group. In the second animal study, mice were fed an alcohol-containing diet for 10days, followed by a 45% high-fat diet with oral administration of BSE (100 or 200mg/day/kg body weight) for 4weeks. Mice in both BSE-fed groups showed reduced hepatic steatosis. In the livers of mice fed BSE, phosphorylation of AMP-activated protein kinase (AMPK) was increased, and expression of hepatic autophagy markers was elevated. In cultured hepatocytes, BSE (200μg/mL) increased the rate of fatty acid oxidation and reduced that of fatty acid synthesis. Taken together, these findings suggest that BSE promotes degradation of lipid droplets and subsequent activation of fat oxidation by activating AMPK in the liver, thus protecting against development of hepatic steatosis in alcohol-fed mice. Saponarin, a major flavonoid in BSE and an activator of AMPK, increased the activity of microsomal triglyceride transfer protein, which suggests that the reduction in hepatic triglyceride levels was mediated by this component of BSE. In conclusion, BSE ameliorated hepatic steatosis in a mouse model of ethanol-induced fatty liver by activating AMPK, an effect possibly mediated by the saponarin component.

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