Kefir peptides prevent high-fructose corn syrup-induced non-alcoholic fatty liver disease in a murine model by modulation of inflammation and the JAK2 signaling pathway

Abstract Objectives Non-alcoholic fatty liver disease (NAFLD) is a chronic metabolic disorder and the most common liver disease in pediatric populations. Epidemiological studies have observed a parallel increase in fructose consumption and incidence of NAFLD among children. The objective of this study was to compare the relative effect of inclusion of isocaloric amounts of high fructose corn syrup (66.5% fructose, 33.5% glucose) versus sucrose (50% fructose, 50% glucose) in the diet for 16 weeks on endpoints of NAFLD and insulin resistance. Methods 30-d-old Iberian pigs were housed in pairs and randomly assigned to receive solid diets (g/kg body weight × d) of 1) control (CON; n = 6): 0 g HFCS, 0 g SUC, and 174.03 kcal metabolizable energy (ME), 2) high-fructose corn syrup (HFCS; n = 8): 31.20 g high-fructose corn syrup, 0 g sucrose and 261 kcal ME, and 3) Sucrose (SUC; n = 6): 0 g high-fructose corn syrup, 24.04 g sucrose and 261 kcal ME for 16 consecutive weeks. Results Compared to CON, both HFCS and SUC diets increased body weight gain (P ≤ 0.001), relative liver weight (P ≤ 0.01) and leptin levels (P ≤ 0.01), and decreased percentage of lean mass composition in the animals (P ≤ 0.001). In addition, HFCS increased fasting insulin levels compared to CON (P ≤ 0.05), and decreased percentage lean mass compared to SUC (P ≤ 0.05). 75% of HFCS and 66.6% of SUC pigs showed histopathological lesions consistent with microvesicular steatosis with periportal or diffuse distribution. Serum markers of liver injury did not differ between diets, and none of the animals developed inflammation, hepatocellular ballooning, Mallory hyaline or necrosis in the liver. Metabolomics analysis revealed liver sorbitol and monosaccharide concentrations were higher in both the HFCS and SUC groups versus CON (P ≤ 0.05), while adenosine monophosphate (AMP) were higher and adenosine diphosphate levels lower in the HFCS and SUC in comparison to CON (P ≤ 0.05). Numerous phosphatidylcholines and sphingomyelins were differentially changed in the HFCS group versus CON (P ≤ 0.05). Conclusions Feeding diets high in either sucrose or high fructose corn syrup promoted obesity and steatosis in the animals. Further research is needed to investigate the mechanisms leading to increased insulin resistance in the HFCS group. Funding Sources ARI #58,873, AcornSeekers, STRIDE.

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High-fructose feeding does not induce steatosis or non-alcoholic fatty liver disease in pigs

Scientific Reports ◽

10.1038/s41598-021-82208-1 ◽

2021 ◽

Vol 11 (1) ◽

Author(s):

Nikolaj H. Schmidt ◽

Pia Svendsen ◽

Julián Albarrán-Juárez ◽

Søren K. Moestrup ◽

Jacob Fog Bentzon

Keyword(s):

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Histopathological Examination ◽

De Novo Lipogenesis ◽

Large Animal ◽

Alcoholic Fatty Liver ◽

High Fructose ◽

Alcoholic Fatty Liver Disease

AbstractNon-alcoholic fatty liver disease (NAFLD) is an increasingly prevalent condition that has been linked to high-fructose corn syrup consumption with induction of hepatic de novo lipogenesis (DNL) as the suggested central mechanism. Feeding diets very high in fructose (> 60%) rapidly induce several features of NAFLD in rodents, but similar diets have not yet been applied in larger animals, such as pigs. With the aim to develop a large animal NAFLD model, we analysed the effects of feeding a high-fructose (HF, 60% w/w) diet for four weeks to castrated male Danish Landrace-York-Duroc pigs. HF feeding upregulated expression of hepatic DNL proteins, but levels were low compared with adipose tissue. No steatosis or hepatocellular ballooning was seen on histopathological examination, and plasma levels of transaminases were similar between groups. Inflammatory infiltrates and the amount of connective tissue was slightly elevated in liver sections from fructose-fed pigs, which was corroborated by up-regulation of macrophage marker expression in liver homogenates. Supported by RNA-profiling, quantitative protein analysis, histopathological examination, and biochemistry, our data suggest that pigs, contrary to rodents and humans, are protected against fructose-induced steatosis by relying on adipose tissue rather than liver for DNL.

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Alleviating effect of Ficus racemosa in high-fat-high-fructose diet-induced non-alcoholic fatty liver disease

Indian Journal of Physiology and Pharmacology ◽

10.25259/ijpp_406_2020 ◽

2021 ◽

Vol 65 ◽

pp. 12-20

Author(s):

Nilay D. Solanki ◽

Kirti Vadi ◽

Sandip Patel

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Lipid Profile ◽

Fatty Liver Disease ◽

High Fat ◽

Alcoholic Fatty Liver ◽

Serum Leptin ◽

High Fructose ◽

Ficus Racemosa ◽

Alcoholic Fatty Liver Disease

Objectives: Non-alcoholic fatty liver disease (NAFLD) is one of the chronic liver diseases. Ficus racemosa has been used for many years in the Ayurvedic medicine system and is closely related with the management of metabolic conditions. The study investigated alleviating effects of methanolic extract of F. racemosa (FRM) bark on high-fat-high-fructose (HFHF) diet -induced NAFLD. Materials and Methods: HFHF-based model was developed for a period of 10 weeks. In treatment groups, FRM (100 mg/kg, 200 mg/kg, and 400 mg/kg) and atorvastatin (20 mg/kg) were administered for 6 weeks after initiating HFHF diet and continued for another 4 weeks. Liver functions test, lipid profile, serum leptin, and antioxidant parameters and histopathology were evaluated. Results: Elevated liver enzymes, lipid markers, and leptin were observed, with significant reduction in antioxidants in disease control rats. FRM treatment significantly improved serum aminotransferase activities, lipid profile, and oxidative changes and brought back to normal. Liver histopathology showed the fatty modifications induced by the HFHF diet, and reduction in fatty changes was observed due to FRM. Significant decline in serum leptin was observed with high-dose FRM. Conclusion: FRM showed positive effects in the reversal of NAFLD and different polyphenolic compounds in the plant were responsible for the proven action.

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Antrodan Alleviates High-Fat and High-Fructose Diet-Induced Fatty Liver Disease in C57BL/6 Mice Model via AMPK/Sirt1/SREBP-1c/PPARγ Pathway

International Journal of Molecular Sciences ◽

10.3390/ijms21010360 ◽

2020 ◽

Vol 21 (1) ◽

pp. 360 ◽

Cited By ~ 6

Author(s):

Charng-Cherng Chyau ◽

Hsueh-Fang Wang ◽

Wen-Juan Zhang ◽

Chin-Chu Chen ◽

Shiau-Huei Huang ◽

...

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Fatty Liver Disease ◽

Mice Model ◽

High Fat ◽

Alcoholic Fatty Liver ◽

High Fructose Diet ◽

High Fructose ◽

Ant Control ◽

Alcoholic Fatty Liver Disease

Non-alcoholic fatty liver disease (NAFLD) and -steatohepatitis (NASH) imply a state of excessive fat built-up in livers with/or without inflammation and have led to serious medical concerns in recent years. Antrodan (Ant), a purified β-glucan from A. cinnamomea has been shown to exhibit tremendous bioactivity, including hepatoprotective, antihyperlipidemic, antiliver cancer, and anti-inflammatory effects. Considering the already well-known alleviating bioactivity of A. cinnamomea for the alcoholic steatohepatitis (ASH), we propose that Ant can be beneficial to NAFLD, and that the AMPK/Sirt1/PPARγ/SREBP-1c pathways may be involved in such alleviations. To uncover this, we carried out this study with 60 male C57BL/6 mice fed high-fat high-fructose diet (HFD) for 60 days, in order to induce NAFLD/NASH. Mice were then grouped and treated (by oral administration) as: G1: control; G2: HFD (HFD control); G3: Ant, 40 mgkg (Ant control); G4: HFD+Orlistat (10 mg/kg) (as Orlistat control); G5: HFD+Ant L (20 mg/kg); and G6: HFD+Ant H (40 mg/kg) for 45 days. The results indicated Ant at 40 mg/kg effectively suppressed the plasma levels of malondialdehyde, total cholesterol, triglycerides, GOT, GPT, uric acid, glucose, and insulin; upregulated leptin, adiponectin, pAMPK, Sirt1, and down-regulated PPARγ and SREBP-1c. Conclusively, Ant effectively alleviates NAFLD via AMPK/Sirt1/CREBP-1c/PPARγ pathway.

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β-patchoulene improves lipid metabolism to alleviate non-alcoholic fatty liver disease via activating AMPK signaling pathway

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2020.111104 ◽

2021 ◽

Vol 134 ◽

pp. 111104

Author(s):

Nan Xu ◽

Huijuan Luo ◽

Minyao Li ◽

Jiazhen Wu ◽

Xue Wu ◽

...

Keyword(s):

Lipid Metabolism ◽

Liver Disease ◽

Fatty Liver ◽

Signaling Pathway ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

Ampk Signaling ◽

Alcoholic Fatty Liver Disease

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Consumption of post-fermented Jing-Wei Fuzhuan brick tea alleviates liver dysfunction and intestinal microbiota dysbiosis in high fructose diet-fed mice

RSC Advances ◽

10.1039/c9ra02473e ◽

2019 ◽

Vol 9 (30) ◽

pp. 17501-17513

Author(s):

Xiangnan Zhang ◽

Qiu Wu ◽

Yan Zhao ◽

Alim Aimy ◽

Xingbin Yang

Keyword(s):

Liver Disease ◽

Fatty Liver ◽

Intestinal Microbiota ◽

Liver Dysfunction ◽

Fatty Liver Disease ◽

Alcoholic Fatty Liver ◽

High Fructose Diet ◽

High Fructose ◽

Alcoholic Fatty Liver Disease

Fuzhuan brick tea can improve non-alcoholic fatty liver disease (NAFLD) and intestinal microbiota imbalance induced by a high fructose diet (HFD) intake in mice.

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