Dietary supplementation with myo -inositol reduces hepatic triglyceride accumulation and expression of both fructolytic and lipogenic genes in rats fed a high-fructose diet

High-fructose feeding impairs copper status and leads to low copper availability, which is a novel mechanism in obesity-related fatty liver. Copper deficiency-associated hepatic iron overload likely plays an important role in fructose-induced liver injury. Excess iron in the liver is distributed throughout hepatocytes and Kupffer cells (KCs). The aim of this study was to examine the role of KCs in the pathogenesis of nonalcoholic fatty liver disease induced by a marginal-copper high-fructose diet (CuMF). Male weanling Sprague-Dawley rats were fed either a copper-adequate or a marginally copper-deficient diet for 4 wk. Deionized water or deionized water containing 30% fructose (wt/vol) was also given ad libitum. KCs were depleted by intravenous administration of gadolinium chloride (GdCl3) before and/or in the middle of the experimental period. Hepatic triglyceride accumulation was completely eliminated with KC depletion in CuMF consumption rats, which was associated with the normalization of elevated plasma monocyte chemoattractant protein-1 (MCP-1) and increased hepatic sterol regulatory element binding protein-1 expression. However, hepatic copper and iron content were not significantly affected by KC depletion. In addition, KC depletion reduced body weight and epididymal fat weight as well as adipocyte size. Plasma endotoxin and gut permeability were markedly increased in CuMF rats. Moreover, MCP-1 was robustly increased in the culture medium when isolated KCs from CuMF rats were treated with LPS. Our data suggest that KCs play a critical role in the development of hepatic steatosis induced by marginal-copper high-fructose diet.

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Maternal Obesogenic Diet Regulates Offspring Bile Acid Homeostasis and Hepatic Lipid Metabolism via the Gut Microbiome in Mice

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00247.2021 ◽

2022 ◽

Author(s):

Michael D. Thompson ◽

Jisue Kang ◽

Austin Faerber ◽

Holly Hinrichs ◽

Oguz Ozler ◽

...

Keyword(s):

Lipid Metabolism ◽

Bile Acid ◽

Mrna Expression ◽

16S Sequencing ◽

Hepatic Expression ◽

Lipogenic Genes ◽

Triglyceride Accumulation ◽

High Fructose ◽

Obesogenic Diet ◽

Donor Offspring

Mice exposed in gestation to maternal high fat/high sucrose (HF/HS) diet develop altered bile acid (BA) homeostasis. We hypothesized that these reflect an altered microbiome and asked if microbiota transplanted from HF/HS offspring change hepatic BA and lipid metabolism to determine the directionality of effect. Female mice were fed HF/HS or chow (CON) for 6 weeks and bred with lean males. 16S sequencing was performed to compare taxa in offspring. Cecal microbiome transplantation (CMT) was performed from HF/HS or CON offspring into antibiotic treated mice fed chow or high fructose. BA, lipid metabolic, and gene expression analyses performed in recipient mice. Gut microbiomes from HF/HS offspring segregated from CON offspring, with increased Firmicutes to Bacteriodetes ratios and Verrucomicrobial abundance. Following CMT, HF/HS recipient mice had larger BA pools, and increased intrahepatic muricholic acid and decreased deoxycholic acid species. HF/HS recipient mice exhibited downregulated hepatic Mrp2, increased hepatic Oatp1b2, and decreased ileal Asbt mRNA expression. HF/HS recipient mice exhibited decreased cecal butyrate and increased hepatic expression of Il6. HF/HS recipient mice had larger livers, and increased intrahepatic triglyceride versus CON recipient mice after fructose feeding, with increased hepatic mRNA expression of lipogenic genes including Srebf1, Fabp1, Mogat1, and Mogat2. CMT from HF/HS offspring increased BA pool and shifted the composition of the intrahepatic BA pool. CMT from HF/HS donor offspring increased fructose-induced liver triglyceride accumulation. These findings support a causal role for vertical transfer of an altered microbiome in hepatic BA and lipid metabolism in HF/HS offspring.

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Sitagliptin Can Prevent the Development of Hepatic Steatosis Due to Inhibiting the Expressions of Hepatic Lipogenic-genes in High-Fructose Diet-Fed Ob/ob Mice

The American Journal of Gastroenterology ◽

10.14309/00000434-201510001-02035 ◽

2015 ◽

Vol 110 ◽

pp. S857-S858

Author(s):

Shinya Fukunishi ◽

Akira Asai ◽

Yasuhiro Tsuda ◽

Kazuhide Higuchi

Keyword(s):

Hepatic Steatosis ◽

High Fructose Diet ◽

Lipogenic Genes ◽

High Fructose

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Blackcurrant Suppresses Metabolic Syndrome Induced by High-Fructose Diet in Rats

Evidence-based Complementary and Alternative Medicine ◽

10.1155/2015/385976 ◽

2015 ◽

Vol 2015 ◽

pp. 1-11 ◽

Cited By ~ 10

Author(s):

Ji Hun Park ◽

Min Chul Kho ◽

Hye Yoom Kim ◽

You Mee Ahn ◽

Yun Jung Lee ◽

...

Keyword(s):

Metabolic Syndrome ◽

Liver Weight ◽

Oral Glucose ◽

Sprague Dawley ◽

High Fructose Diet ◽

Reactive Protein ◽

Triglyceride Accumulation ◽

High Fructose ◽

Amp Activated Protein Kinase

Increased fructose ingestion has been linked to obesity, hyperglycemia, dyslipidemia, and hypertension associated with metabolic syndrome. Blackcurrant (Ribes nigrum; BC) is a horticultural crop in Europe. To induce metabolic syndrome, Sprague-Dawley rats were fed 60% high-fructose diet. Treatment with BC (100 or 300 mg/kg/day for 8 weeks) significantly suppressed increased liver weight, epididymal fat weight, C-reactive protein (CRP), total bilirubin, leptin, and insulin in rats with induced metabolic syndrome. BC markedly prevented increased adipocyte size and hepatic triglyceride accumulation in rats with induced metabolic syndrome. BC suppressed oral glucose tolerance and protein expression of insulin receptor substrate-1 (IRS-1) and phosphorylated AMP-activated protein kinase (p-AMPK) in muscle. BC significantly suppressed plasma total cholesterol, triglyceride, and LDL content. BC suppressed endothelial dysfunction by inducing downregulation of endothelin-1 and adhesion molecules in the aorta. Vascular relaxation of thoracic aortic rings by sodium nitroprusside and acetylcholine was improved by BC. The present study provides evidence of the potential protective effect of BC against metabolic syndrome by demonstrating improvements in dyslipidemia, hypertension, insulin resistance, and obesityin vivo.

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