The modulation of Luffa cylindrica (L.) Roem supplementation on gene expression and amino acid profiles in liver for alleviating hepatic steatosis via gut microbiota in high-fat diet-fed mice: insight from hepatic transcriptome analysis

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

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Peripancreatic adipose tissue protects against high-fat-diet-induced hepatic steatosis and insulin resistance in mice

International Journal of Obesity ◽

10.1038/s41366-020-00657-6 ◽

2020 ◽

Vol 44 (11) ◽

pp. 2323-2334

Author(s):

Belén Chanclón ◽

Yanling Wu ◽

Milica Vujičić ◽

Marco Bauzá-Thorbrügge ◽

Elin Banke ◽

...

Keyword(s):

Gene Expression ◽

Insulin Resistance ◽

Adipose Tissue ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Obese Mice ◽

High Fat ◽

Insulin Levels ◽

Fat Depots ◽

Fat Depot

Abstract Background/objectives Visceral adiposity is associated with increased diabetes risk, while expansion of subcutaneous adipose tissue may be protective. However, the visceral compartment contains different fat depots. Peripancreatic adipose tissue (PAT) is an understudied visceral fat depot. Here, we aimed to define PAT functionality in lean and high-fat-diet (HFD)-induced obese mice. Subjects/methods Four adipose tissue depots (inguinal, mesenteric, gonadal, and peripancreatic adipose tissue) from chow- and HFD-fed male mice were compared with respect to adipocyte size (n = 4–5/group), cellular composition (FACS analysis, n = 5–6/group), lipogenesis and lipolysis (n = 3/group), and gene expression (n = 6–10/group). Radioactive tracers were used to compare lipid and glucose metabolism between these four fat depots in vivo (n = 5–11/group). To determine the role of PAT in obesity-associated metabolic disturbances, PAT was surgically removed prior to challenging the mice with HFD. PAT-ectomized mice were compared to sham controls with respect to glucose tolerance, basal and glucose-stimulated insulin levels, hepatic and pancreatic steatosis, and gene expression (n = 8–10/group). Results We found that PAT is a tiny fat depot (~0.2% of the total fat mass) containing relatively small adipocytes and many “non-adipocytes” such as leukocytes and fibroblasts. PAT was distinguished from the other fat depots by increased glucose uptake and increased fatty acid oxidation in both lean and obese mice. Moreover, PAT was the only fat depot where the tissue weight correlated positively with liver weight in obese mice (R = 0.65; p = 0.009). Surgical removal of PAT followed by 16-week HFD feeding was associated with aggravated hepatic steatosis (p = 0.008) and higher basal (p < 0.05) and glucose-stimulated insulin levels (p < 0.01). PAT removal also led to enlarged pancreatic islets and increased pancreatic expression of markers of glucose-stimulated insulin secretion and islet development (p < 0.05). Conclusions PAT is a small metabolically highly active fat depot that plays a previously unrecognized role in the pathogenesis of hepatic steatosis and insulin resistance in advanced obesity.

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Developmental bisphenol A (BPA) exposure leads to sex-specific modification of hepatic gene expression and epigenome at birth that may exacerbate high-fat diet-induced hepatic steatosis

Toxicology and Applied Pharmacology ◽

10.1016/j.taap.2015.02.021 ◽

2015 ◽

Vol 284 (2) ◽

pp. 101-112 ◽

Cited By ~ 73

Author(s):

Rita S. Strakovsky ◽

Huan Wang ◽

Nicki J. Engeseth ◽

Jodi A. Flaws ◽

William G. Helferich ◽

...

Keyword(s):

Gene Expression ◽

Bisphenol A ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Hepatic Gene Expression ◽

High Fat ◽

Specific Modification

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Coumarin attenuates hepatic steatosis by down-regulating lipogenic gene expression in mice fed a high-fat diet

British Journal Of Nutrition ◽

10.1017/s0007114512005260 ◽

2013 ◽

Vol 109 (9) ◽

pp. 1590-1597 ◽

Cited By ~ 23

Author(s):

Min Young Um ◽

Mi Kyeong Moon ◽

Jiyun Ahn ◽

Tae Youl Ha

Keyword(s):

Gene Expression ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Fatty Acid Synthase ◽

Binding Protein ◽

Regulatory Element ◽

Thiobarbituric Acid Reactive Substance ◽

High Fat ◽

Lipogenic Gene ◽

Lipogenic Gene Expression

Coumarin is a natural compound abundant in plant-based foods such as citrus fruits, tomatoes, vegetables and green tea. Although coumarin has been reported to exhibit anti-coagulant, anti-inflammation and cholesterol-lowering properties, the effect of coumarin on hepatic lipid metabolism remains unclear. In the present study, we evaluated the ability of coumarin to protect against hepatic steatosis associated with a high-fat diet (HFD) and investigated potential mechanisms underlying this effect. C57BL/6J mice were fed a normal diet, HFD and HFD containing 0·05 % courmarin for 8 weeks. The present results showed that coumarin reduced weight gain and abdominal fat mass in mice fed the HFD for 8 weeks (P< 0·05). Coumarin also significantly reduced the HFD-induced elevation in total cholesterol, apoB, leptin and insulin (P< 0·05). In the liver of HFD-fed mice, coumarin significantly reduced total lipids, TAG and cholesterol (38, 22 and 9 % reductions, respectively; P< 0·05), as well as lipid droplet number and size. Additionally, thiobarbituric acid-reactive substance levels, as an indicator of hepatic steatosis, were attenuated by coumarin (P< 0·05). Finally, coumarin suppressed the HFD-induced up-regulation in fatty acid synthase (FAS) activity, and the expression of sterol regulatory element-binding protein-1, FAS, acetyl-CoA carboxylase 1, PPARγ and CCAAT/enhancer-binding protein-α in the liver. Taken together, these results demonstrate that coumarin could prevent HFD-induced hepatic steatosis by regulating lipogenic gene expression, suggesting potential targets for preventing hepatic steatosis.

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EGCG Prevents High Fat Diet-Induced Changes in Gut Microbiota, Decreases of DNA Strand Breaks, and Changes in Expression and DNA Methylation ofDnmt1andMLH1in C57BL/6J Male Mice

Oxidative Medicine and Cellular Longevity ◽

10.1155/2017/3079148 ◽

2017 ◽

Vol 2017 ◽

pp. 1-17 ◽

Cited By ~ 37

Author(s):

Marlene Remely ◽

Franziska Ferk ◽

Sonja Sterneder ◽

Tahereh Setayesh ◽

Sylvia Roth ◽

...

Keyword(s):

Gene Expression ◽

Dna Methylation ◽

Dna Damage ◽

Gut Microbiota ◽

High Fat Diet ◽

Dna Methyltransferase ◽

Dna Methyltransferase 1 ◽

Male Mice ◽

High Fat ◽

Methyltransferase 1

Obesity as a multifactorial disorder involves low-grade inflammation, increased reactive oxygen species incidence, gut microbiota aberrations, and epigenetic consequences. Thus, prevention and therapies with epigenetic active antioxidants, (-)-Epigallocatechin-3-gallate (EGCG), are of increasing interest. DNA damage, DNA methylation and gene expression ofDNA methyltransferase 1,interleukin 6, andMutL homologue 1were analyzed in C57BL/6J male mice fed a high-fat diet (HFD) or a control diet (CD) with and without EGCG supplementation. Gut microbiota was analyzed with quantitative real-time polymerase chain reaction. An induction of DNA damage was observed, as a consequence of HFD-feeding, whereas EGCG supplementation decreased DNA damage. HFD-feeding induced a higher inflammatory status. Supplementation reversed these effects, resulting in tissue specific gene expression and methylation patterns ofDNA methyltransferase 1andMutL homologue 1. HFD feeding caused a significant lower bacterial abundance. TheFirmicutes/Bacteroidetesratio is significantly lower in HFD + EGCG but higher in CD + EGCG compared to control groups. The results demonstrate the impact of EGCG on the one hand on gut microbiota which together with dietary components affects host health. On the other hand effects may derive from antioxidative activities as well as epigenetic modifications observed on CpG methylation but also likely to include other epigenetic elements.

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Effect of a long-term high-protein diet on survival, obesity development, and gut microbiota in mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00363.2015 ◽

2016 ◽

Vol 310 (11) ◽

pp. E886-E899 ◽

Cited By ~ 25

Author(s):

Pia Kiilerich ◽

Lene Secher Myrmel ◽

Even Fjære ◽

Qin Hao ◽

Floor Hugenholtz ◽

...

Keyword(s):

Gene Expression ◽

Adipose Tissue ◽

Gut Microbiota ◽

Dietary Fat ◽

High Fat Diet ◽

High Fat ◽

Low Fat ◽

Low Fat Diet ◽

Low Protein

Female C57BL/6J mice were fed a regular low-fat diet or high-fat diets combined with either high or low protein-to-sucrose ratios during their entire lifespan to examine the long-term effects on obesity development, gut microbiota, and survival. Intake of a high-fat diet with a low protein/sucrose ratio precipitated obesity and reduced survival relative to mice fed a low-fat diet. By contrast, intake of a high-fat diet with a high protein/sucrose ratio attenuated lifelong weight gain and adipose tissue expansion, and survival was not significantly altered relative to low-fat-fed mice. Our findings support the notion that reduced survival in response to high-fat/high-sucrose feeding is linked to obesity development. Digital gene expression analyses, further validated by qPCR, demonstrated that the protein/sucrose ratio modulated global gene expression over time in liver and adipose tissue, affecting pathways related to metabolism and inflammation. Analysis of fecal bacterial DNA using the Mouse Intestinal Tract Chip revealed significant changes in the composition of the gut microbiota in relation to host age and dietary fat content, but not the protein/sucrose ratio. Accordingly, dietary fat rather than the protein/sucrose ratio or adiposity is a major driver shaping the gut microbiota, whereas the effect of a high-fat diet on survival is dependent on the protein/sucrose ratio.

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Liraglutide Attenuates Nonalcoholic Fatty Liver Disease by Modulating Gut Microbiota in Rats Administered a High-Fat Diet

BioMed Research International ◽

10.1155/2020/2947549 ◽

2020 ◽

Vol 2020 ◽

pp. 1-10

Author(s):

Ningjing Zhang ◽

Junxian Tao ◽

Lijun Gao ◽

Yan Bi ◽

Ping Li ◽

...

Keyword(s):

Liver Disease ◽

Gut Microbiota ◽

Fatty Liver ◽

Nonalcoholic Fatty Liver Disease ◽

Hepatic Steatosis ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Structural Changes ◽

High Fat ◽

Nonalcoholic Fatty Liver

This study aimed to determine whether modulation of the gut microbiota structure by liraglutide helps improve nonalcoholic fatty liver disease (NAFLD) in rats on a high-fat diet (HFD). Rats were administered an HFD for 12 weeks to induce NAFLD and then administered liraglutide for 4 additional weeks. Next-generation sequencing and multivariate analysis were performed to assess structural changes in the gut microbiota. Liraglutide attenuated excessive hepatic ectopic fat deposition, maintained intestinal barrier integrity, and alleviated metabolic endotoxemia in HFD rats. Liraglutide significantly altered the overall structure of the HFD-disrupted gut microbiota and gut microbial composition in HFD rats in comparison to those on a normal diet. An abundance of 100 operational taxonomic units (OTUs) were altered upon liraglutide administration, with 78 OTUs associated with weight gain or inflammation. Twenty-three OTUs positively correlated with hepatic steatosis-related parameters were decreased upon liraglutide intervention, while 5 OTUs negatively correlated with hepatic steatosis-related parameters were increased. These results suggest that liraglutide-mediated attenuation of NAFLD partly results from structural changes in gut microbiota associated with hepatic steatosis.

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Raspberry Polyphenol Extracts Modify Physiological Parameters and the Hepatic Transcriptome of C57BL/6J Mice Fed a High-Fat Diet

Current Developments in Nutrition ◽

10.1093/cdn/nzaa045_085 ◽

2020 ◽

Vol 4 (Supplement_2) ◽

pp. 452-452

Author(s):

Gavin Pierce ◽

Mariana Buranelo Egea ◽

Neil Shay

Keyword(s):

Gene Expression ◽

Energy Efficiency ◽

Expression Analysis ◽

High Fat Diet ◽

Fasting Blood Glucose ◽

Differential Expression Analysis ◽

Hepatic Gene Expression ◽

High Fat ◽

Treatment Groups ◽

Hepatic Transcriptome

Abstract Objectives Red raspberries are rich in polyphenols, fiber, and volatile compounds, and have been demonstrated to have favorable effects on energy homeostasis in mice. We made two extracts from red raspberries, enriched in either hydrophilic (R25) or hydrophobic (R80) polyphenols. We tested the hypothesis that these polyphenol extracts would differentially alter and improve physiological measures and the hepatic transcriptome of C57BL/6J male mice fed a obesigenic high fat diet (HF). Methods Raspberry polyphenol extracts were obtained using FPX-66 resin, and eluting with 25% (R25) and 80% (R80) ethanol (v/v); eluates were then dried. Mice were provided a low fat diet (LF, 10% kcal fat, n = 12), high fat diet (HF, 45% kcal fat, n = 12), HF with raspberry puree concentrate (RPC, n = 8), HF with R25 (n = 8), or HF with R80 (n = 8) ad libitum for 10 weeks. Body weights, food intake, and fasting glucose levels were measured. Post mortem, serum was collected for ELISA, organ weights were recorded, and liver tissue was collected for triglyceride analysis and differential expression analysis. Results Energy efficiency and liver weights in the R25 and R80 groups were intermediate to the LF and HF controls. Fasting blood glucose, serum triglycerides, and adipose tissue weights did not differ between treatment groups. A trend toward significance was seen in reduction of weight gain in the raspberry treatment groups. Differential gene expression analysis revealed that the R25 diet acted agonistically towards the constitutive androstane receptor (CAR) and reduced the relative levels of several sterol regulatory binding protein-regulated genes. Notably, the R80 diet robustly increased levels of Cyp4a14, a peroxisome proliferator-activated receptor alpha (PPAR-α)-regulated gene. Conclusions Supplementation of a high fat diet with raspberry polyphenol extracts modified hepatic gene expression and energy efficiency in C57BL/6J mice. The two extracts had a differential impact on hepatic gene expression. For example, the R25 extract behaved as an agonist for CAR, while the R80 extract behaved as an agonist for PPAR-α. These findings suggest that select polyphenols found within red raspberries may serve as nutraceuticals that specifically act via PPAR-α, CAR, and other targets in liver. Funding Sources National Processed Raspberry Commission and Washington Red Raspberry Commission.

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