scholarly journals Soybean oil attenuates the onset of non-alcoholic steatohepatitis and insulin resistance

2020 ◽  
Vol 79 (OCE2) ◽  
Author(s):  
Victor Sanchez ◽  
Anna Janina Engstler ◽  
Annette Brandt ◽  
Cheng Jun Jin ◽  
Dragana Rajcic ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Soybean Oil ◽  
Mrna Expression ◽  
Liver Tissue ◽  
Metabolic Diseases ◽  
Insulin Receptors ◽  
Signaling Cascade ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Tlr4 Mrna

AbstractBackground and Aims:General overnutrition, and a diet rich in fat and sugar are among the key risk factors for the development of metabolic diseases including diabetes type 2 and non-alcoholic fatty liver diseases (NAFLD). While being among the most commonly consumed oils world-wide, the effects of soybean oil on the development of metabolic diseases are yet not understood. Indeed, existing data is in part contradictory. Based on this background, the aim of the present study was to investigate the effects of soybean oil consumption on the development of non-alcoholic steatohepatitis (NASH), the more progressed stage of NAFLD, and insulin resistance.Methods:Female C57BL/6J mice were fed either a liquid standard control diet (C) or a liquid fat-, fructose- and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt/wt) fructose, 0.155% (wt/wt) cholesterol) or a FFC supplemented with soybean oil (FFC + S, 21E% butterfat + 4E% soy oil), with FFC and FFC + S-fed groups being pair fed for 13 weeks to induce steatohepatitis. After 7 and 12 weeks of feeding, a glucose tolerance test was performed. Indicators of liver damage, inflammation, intestinal barrier function and markers of insulin signaling cascade were measured in intestinal, liver and muscle tissue.Results:As expected FFC-fed mice developed early signs of NASH and insulin resistance. Despite similar caloric intake and body weight gain, development of NASH and insulin resistance were significantly attenuated in FFC + S-fed mice when compared to FFC-fed animals. Indeed, signs of hepatic inflammation e.g. number of inflammatory foci and neutrophils as well as activity of transaminase in plasma were almost at the level of control in FFC + S-fed mice. Prevalence of macrovesicular steatosis being the predominant type of fat accumulation found in FFC-fed animals was also markedly lower in FFC + S-fed mice. Furthermore, while in muscle and liver tissue of FFC-fed mice insulin receptors mRNA expression was significantly different from C-fed animals, insulin receptors expression in FFC + S-fed mice was almost at the level of controls. The protective effects of soybean oil supplementation on the development of metabolic alterations were associated with a protection against the induction of TLR4 mRNA expression and dependent signaling molecules in liver tissue.Conclusion:Taking together, our results indicate that supplementation with soybean oil may attenuate the development of diet-induced NASH and insulin resistance in mice and that this may be related to alteration of TLR4-dependent signaling cascade in liver tissue. (Funded in parts by UFOP e.V.)

scholarly journals Dual-specificity phosphatase 3 deletion promotes obesity, non-alcoholic steatohepatitis and hepatocellular carcinoma

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Sophie Jacques ◽  
Arash Arjomand ◽  
Hélène Perée ◽  
Patrick Collins ◽  
Alice Mayer ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Liver Damage ◽  
Chow Diet ◽  
Serum Triglycerides ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Dual Specificity ◽  
Dual Specificity Protein Phosphatase

AbstractNon-alcoholic fatty liver disease (NAFLD) is the most common chronic hepatic pathology in Western countries. It encompasses a spectrum of conditions ranging from simple steatosis to more severe and progressive non-alcoholic steatohepatitis (NASH) that can lead to hepatocellular carcinoma (HCC). Obesity and related metabolic syndrome are important risk factors for the development of NAFLD, NASH and HCC. DUSP3 is a small dual-specificity protein phosphatase with a poorly known physiological function. We investigated its role in metabolic syndrome manifestations and in HCC using a mouse knockout (KO) model. While aging, DUSP3-KO mice became obese, exhibited insulin resistance, NAFLD and associated liver damage. These phenotypes were exacerbated under high fat diet (HFD). In addition, DEN administration combined to HFD led to rapid HCC development in DUSP3-KO compared to wild type (WT) mice. DUSP3-KO mice had more serum triglycerides, cholesterol, AST and ALT compared to control WT mice under both regular chow diet (CD) and HFD. The level of fasting insulin was higher compared to WT mice, though, fasting glucose as well as glucose tolerance were normal. At the molecular level, HFD led to decreased expression of DUSP3 in WT mice. DUSP3 deletion was associated with increased and consistent phosphorylation of the insulin receptor (IR) and with higher activation of the downstream signaling pathway. In conclusion, our results support a new role for DUSP3 in obesity, insulin resistance, NAFLD and liver damage.

scholarly journals Non-alcoholic steatohepatitis in patients with endocrine pathology. Review

2021 ◽  
pp. 82-93
Author(s):  
S. M. Tkach ◽  
Т. L. Cheverda
Keyword(s):  
Insulin Resistance ◽  
Polycystic Ovary ◽  
Hormone Deficiency ◽  
Endocrine Disorders ◽  
Male Hypogonadism ◽  
Pathophysiological Mechanism ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Intestinal Dysbiosis ◽  
Obstructive Sleep

Non-alcoholic steatohepatitis (NASH) is a subtype of non-alcoholic fatty liver disease (NAFLD), which in the absence of treatment can progress to the development of cirrhosis and hepatocellular carcinoma, as well as to increased mortality associated with these diseases. The main risk factors for the development of NAFLD and NASH are the presence of insulin resistance and obesity. Quite often NAFLD and NASH are associated with so-called extrahepatic manifestations, such as obstructive sleep apnea, hypertension, dyslipidemia, intestinal dysbiosis, genetic predisposition, sedentary lifestyle and consumption of certain foods. However, NAFLD and NASH are also associated with some endocrine diseases and conditions, including type 2 diabetes, polycystic ovary syndrome, hypothyroidism, male hypogonadism, growth hormone deficiency or excess, hypercortisolism, vitamin D or prolactin deficiency. In many of these diseases, the key pathophysiological mechanism is insulin resistance. This review considers the putative pathophysiological mechanisms that play an important pathogenetic role in the development of NASH in these endocrine disorders.Unfortunately, our understanding of the pathophysiology of NAFLD in various endocrinopathies is far from complete. In addition, the natural course of NAFLD due to endocrine disorders compared to the course and consequences of “primary” NAFLD is still poorly understood. Therefore, in the coming years, further research into the pathophysiology and clinical features of NASH will be important to better understand the relationship between different endocrinopathies and NAFLD, which will help improve the treatment of this pathology.

scholarly journals XBP1s Is an Anti-lipogenic Protein

2016 ◽  
Vol 291 (33) ◽  
pp. 17394-17404 ◽  
Author(s):  
Hilde Herrema ◽  
Yingjiang Zhou ◽  
Dongyan Zhang ◽  
Justin Lee ◽  
Mario Andres Salazar Hernandez ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Transcription Factor ◽  
Fatty Liver ◽  
Er Stress ◽  
Metabolic Diseases ◽  
Synthesis Rate ◽  
Alcoholic Fatty Liver ◽  
Lipogenic Gene ◽  
Lipogenic Gene Expression

Endoplasmic reticulum (ER) stress has been shown to contribute to various metabolic diseases, including non-alcoholic fatty liver disease and type 2 diabetes. Reduction of ER stress by treatment with chemical chaperones or overexpression of ER chaperone proteins alleviates hepatic steatosis. Nonetheless, X-box binding protein 1s (XBP1s), a key transcription factor that reduces ER stress, has been proposed as a lipogenic transcription factor. In this report, we document that XBP1s leads to suppression of lipogenic gene expression and reduction of hepatic triglyceride and diacylglycerol content in livers of diet-induced obese and genetically obese and insulin-resistant ob/ob mice. Furthermore, we also show that PKCϵ activity, which correlates with fatty liver and which causes insulin resistance, was significantly reduced in diet-induced obese mice. Finally, we have shown that XBP1s reduces the hepatic fatty acid synthesis rate and enhances macrolipophagy, an initiating step in lipolysis. Our results reveal that XBP1s reduces hepatic lipogenic gene expression and improves hepatosteatosis in mouse models of obesity and insulin resistance, which leads us to conclude that XBP1s has anti-lipogenic properties in the liver.

scholarly journals Non-Coding RNAs: Novel Players in Insulin Resistance and Related Diseases

2021 ◽  
Vol 22 (14) ◽  
pp. 7716
Author(s):  
Caterina Formichi ◽  
Laura Nigi ◽  
Giuseppina Emanuela Grieco ◽  
Carla Maccora ◽  
Daniela Fignani ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Metabolic Diseases ◽  
Gene Expression Regulation ◽  
Biological Fluids ◽  
Current Evidence ◽  
Alcoholic Fatty Liver ◽  
Non Coding Rnas ◽  
Alcoholic Fatty Liver Disease

The rising prevalence of metabolic diseases related to insulin resistance (IR) have stressed the urgent need of accurate and applicable tools for early diagnosis and treatment. In the last decade, non-coding RNAs (ncRNAs) have gained growing interest because of their potential role in IR modulation. NcRNAs are variable-length transcripts which are not translated into proteins but are involved in gene expression regulation. Thanks to their stability and easy detection in biological fluids, ncRNAs have been investigated as promising diagnostic and therapeutic markers in metabolic diseases, such as type 2 diabetes mellitus (T2D), obesity and non-alcoholic fatty liver disease (NAFLD). Here we review the emerging role of ncRNAs in the development of IR and related diseases such as obesity, T2D and NAFLD, and summarize current evidence concerning their potential clinical application.

scholarly journals Fructo-Oligosaccharides Ameliorate Steatohepatitis, Visceral Adiposity, and Associated Chronic Inflammation via Increased Production of Short-Chain Fatty Acids in a Mouse Model of Non-alcoholic Steatohepatitis

2020 ◽  
Author(s):  
Atsuko Takai ◽  
Kentaro Kikuchi ◽  
Mayuko Ichimura ◽  
Koichi Tsuneyama ◽  
Yuki Moritoki ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Model ◽  
Mrna Expression ◽  
Chronic Inflammation ◽  
Propionic Acid ◽  
Visceral Adiposity ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Epididymal Fat ◽  
Metabolism Enzymes

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. Methods: Twelve newborn C57BL/6J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. Results: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001). Conclusions: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production .

scholarly journals Fructo-Oligosaccharides Ameliorate Steatohepatitis, Visceral Adiposity, and Associated Chronic Inflammation via Increased Production of Short-Chain Fatty Acids in a Mouse Model of Non-alcoholic Steatohepatitis

2019 ◽  
Author(s):  
Atsuko Takai ◽  
Kentaro Kikuchi ◽  
Mayuko Ichimura ◽  
Koichi Tsuneyama ◽  
Yuki Moritoki ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Mouse Model ◽  
Mrna Expression ◽  
Chronic Inflammation ◽  
Propionic Acid ◽  
Visceral Adiposity ◽  
Alcoholic Fatty Liver ◽  
Alcoholic Steatohepatitis ◽  
Epididymal Fat ◽  
Metabolism Enzymes

Abstract Background: Non-alcoholic fatty liver disease (NAFLD) is a hepatic manifestation of metabolic syndrome. Within the spectrum of NAFLD, non-alcoholic steatohepatitis (NASH) in combination with hepatic inflammation and fibrosis can lead to liver cirrhosis and hepatocellular carcinoma. Dysbiosis was reported to contribute to NASH pathogenesis. This study aimed to determine the effects of fructo-oligosaccharides (FOS) on steatohepatitis and visceral adiposity in an obese mouse model of NASH. Methods: Twelve newborn C57BL/6J male mice were subcutaneously injected with monosodium glutamate (MSG) to induce obesity on a conventional diet. Six mice were also administered 5% FOS via drinking water from 10 weeks of age. At 18 weeks, histological characteristics of the liver and epididymal fat were compared between the groups. Hepatic mRNA expression of lipid metabolism enzymes and SCFA in feces and sera were measured. Results: Hepatic steatosis, inflammatory cell infiltration, and hepatocyte ballooning in the liver and increased hepatic mRNA expression of fatty acid synthase and glycerol-3-phosphate acyltransferase were observed in the MSG-treated mice. FOS treatment improved the liver pathology and blunted the increases in the mRNA expression levels of lipid metabolism enzymes. In addition, FOS inhibited adipocyte enlargement and formation of crown-like structures and reduced the M1 macrophage frequency in the epididymal fat of the MSG mice (39.4% ± 3.0% vs. 22.8% ± 0.7%; P = 0.001). FOS increased not only the fecal concentrations of n-butyric acid (0.04 ± 0.01 vs. 0.38 ± 0.14 mg/g, P = 0.02), propionic acid (0.09 ± 0.03 vs. 0.42 ± 0.16 mg/g, P = 0.02), and acetic acid (0.65 ± 0.16 vs. 1.48 ± 0.29 mg/g, P = 0.03) but also the serum concentration of propionic acid (3.9 ± 0.5 vs. 8.2 ± 0.5 μmol/L, P = 0.001). Conclusions: FOS ameliorates steatohepatitis, visceral adiposity, and chronic inflammation by increasing SCFA production .

scholarly journals Fortifying Butterfat with Soybean Oil Attenuates the Onset of Diet-Induced Non-Alcoholic Steatohepatitis and Glucose Intolerance

Nutrients ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 959
Author(s):  
Victor Sánchez ◽  
Annette Brandt ◽  
Cheng Jun Jin ◽  
Dragana Rajcic ◽  
Anna Janina Engstler ◽  
...  
Keyword(s):  
Soybean Oil ◽  
Mrna Expression ◽  
Glucose Intolerance ◽  
Barrier Function ◽  
Control Diet ◽  
Saturated Fatty Acids ◽  
Interleukin 1 ◽  
Intestinal Barrier ◽  
Intestinal Barrier Function ◽  
Alcoholic Steatohepatitis

The addition of plant oils such as soybean oil (S) to a diet rich in saturated fatty acids is discussed as a possible route to prevent or diminish the development of metabolic disease. Here, we assessed whether a butterfat-rich diet fortified with S affects the development of early non-alcoholic steatohepatitis (NASH) and glucose intolerance. Female C57BL/6J mice were fed a standard-control diet (C); a fat-, fructose-, and cholesterol-rich diet (FFC, 25E% butterfat, 50% (wt./wt.) fructose, 0.16% (wt./wt.) cholesterol); or FFC supplemented with S (FFC + S, 21E% butterfat + 4E% S) for 13 weeks. Indicators of liver damage, inflammation, intestinal barrier function, and glucose metabolism were measured. Lipopolysaccharide (LPS)-challenged J774A.1 cells were incubated with linolenic and linoleic acids (ratio 1:7.1, equivalent to S). The development of early NASH and glucose intolerance was significantly attenuated in FFC + S–fed mice compared to FFC-fed mice associated with lower hepatic toll-like receptor-4 mRNA expression, while markers of intestinal barrier function were significantly higher than in C-fed mice. Linolenic and linoleic acid significantly attenuated LPS-induced formation of reactive nitrogen species and interleukin-1 beta mRNA expression in J774A.1 cells. Our results indicate that fortifying butterfat with S may attenuate the development of NASH and glucose intolerance in mice.

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