Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats

Vasiljević, Ana; Bursać, Biljana; Djordjević, Ana; Milutinović, Danijela Vojnović; Nikolić, Marina; Matić, Gordana; Veličković, Nataša

doi:10.1007/s00394-013-0641-4

Cited by 41 publications

(36 citation statements)

References 51 publications

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“…Since the increase in SOD2 activity in fructose‐fed rats was not accompanied by increased expression or enhanced activity of other antioxidant enzymes or damage of cellular macromolecules, we can assume that the expected rise in concentration of hydrogen peroxide represents a transient and regulated stage during the adaptation to nutritional excess. Using the same animal model, we have previously observed that high‐fructose diet impairs hepatic insulin sensitivity; therefore the absence of oxidative stress observed herein suggests that the rise in hydrogen peroxide concentration in the liver of fructose‐fed rats might represent a cellular response aimed to restore hepatic insulin sensitivity at the early stage of the disease. However, the possibility that prolonged fructose overconsumption might finally lead to oxidative stress, and consequently contribute to progression and aggravation of metabolic disturbances in later adulthood, should also be investigated.…”

Section: Discussionsupporting

confidence: 55%

The expression and activity of antioxidant enzymes in the liver of rats exposed to high‐fructose diet in the period from weaning to adulthood

et al. 2014

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Section: Discussionsupporting

confidence: 55%

The expression and activity of antioxidant enzymes in the liver of rats exposed to high‐fructose diet in the period from weaning to adulthood

et al. 2014

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“…Daily fructose consumption from food or drinking water has been demonstrated to stimulate de novo lipogenesis and results in chronic low-grade inflammation and insulin resistance. 38, 39 Previous studies have suggested that NAFLD may be associated with an increased formation of reactive oxygen species in the liver and an induction of TNFα. 40 Recent study showed that lipid peroxidation results in the formation of HNE and upregulates various signaling intermediates that regulate cellular activity and dysfunction via a process called redox signaling.…”

Section: Discussionmentioning

confidence: 99%

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

Chen

Tsai

et al. 2016

Nutr & Diabetes

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Objective:In recent years, people have changed their eating habits, and high-fructose-containing bubble tea has become very popular. High-fructose intake has been suggested to be a key factor that induces non-alcoholic fatty liver disease (NAFLD). Kefir, a fermented milk product composed of microbial symbionts, has demonstrated numerous biological activities, including antibacterial, antioxidant and immunostimulating effects. The present study aims to evaluate the effects of kefir peptides on high-fructose-induced hepatic steatosis and the possible molecular mechanism.Results:An animal model of 30% high-fructose-induced NAFLD in C57BL/6J mice was established. The experiment is divided into the following six groups: (1) normal: H2O drinking water; (2) mock: H2O+30% fructose; (3) KL: low-dose kefir peptides (50 mg kg−1)+30% fructose; (4) KM: medium-dose kefir peptides (100 mg kg−1)+30% fructose; (5) KH: high-dose kefir peptides (150 mg kg−1)+30% fructose; and (6) CFM: commercial fermented milk (100 mg kg−1)+30% fructose. The results show that kefir peptides improve fatty liver syndrome by decreasing body weight, serum alanine aminotransferase, triglycerides, insulin and hepatic triglycerides, cholesterol, and free fatty acids as well as the inflammatory cytokines (TNF-α, IL-6 and IL-1β) that had been elevated in fructose-induced NAFLD mice. In addition, kefir peptides markedly increased phosphorylation of AMPK to downregulate its targeted enzymes, ACC (acetyl-CoA carboxylase) and SREBP-1c (sterol regulatory element-binding protein 1), and inhibited de novo lipogenesis. Furthermore, kefir peptides activated JAK2 to stimulate STAT3 phosphorylation, which can translocate to the nucleus, and upregulated several genes, including the CPT1 (carnitine palmitoyltransferase-1) involved in fatty acid oxidation.Conclusion:Our data have demonstrated that kefir peptides can improve the symptoms of NAFLD, including body weight, energy intake, inflammatory reaction and the formation of fatty liver by activating JAK2 signal transduction through the JAK2/STAT3 and JAK2/AMPK pathways in the high-fructose-induced fatty liver animal model. Therefore, kefir peptides may have the potential for clinical application for the prevention or treatment of clinical metabolic syndrome.

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“…Thus, high fructose consumption in rats results in hepatic increase of TNFα mRNA expression via NFκβ-dependent transcriptional upregulation 112 . TNFα induces serine phosphorylation of IRS-1 through inhibition of serine phosphatases (such as protein phosphatase 2A or PP2A) or activation of serine kinases (such as JNK or protein kinase C theta) leading to disruption of insulin signaling in the liver 113 .…”

Section: ) Harmful Effects Of Hepatotoxic Carbohydratesmentioning

confidence: 99%

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

et al. 2016

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The exposure of hepatocytes to high concentrations of lipids and carbohydrates and the ensuing hepatocellular injury are termed lipotoxicity and glucotoxicity, respectively. A common denominator is metabolic derangement, especially in regards to intracellular energy homeostasis, which is brought on by glucose intolerance and insulin resistance in tissues. In this review, we highlight the lipids and carbohydrates that provoke hepatocyte injury and the mechanisms involved in lipotoxicity and glucotoxicity, including endoplasmic reticulum stress, oxidative stress and mitochondrial impairment. Through upregulation of proteins involved in various pathways including PKR-like ER kinase (PERK), CCAAT/enhancer-binding homologous protein (CHOP), c-Jun NH2-terminal kinase-1 (JNK), Bcl-2 interacting mediator (BIM), p53 upregulated modulator of apoptosis (PUMA), and eventually caspases, hepatocytes in lipotoxic states ultimately undergo apoptosis. The protective role of certain lipids and possible targets for pharmacological therapy are explored. Finally, we discuss the role of high fructose and glucose diets in contributing to organelle impairment and poor glucose transport mechanisms, which perpetuate hyperglycemia and hyperlipidemia by shunting of excess carbohydrates into lipogenesis.

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Hepatic inflammation induced by high-fructose diet is associated with altered 11βHSD1 expression in the liver of Wistar rats

Cited by 41 publications

References 51 publications

The expression and activity of antioxidant enzymes in the liver of rats exposed to high‐fructose diet in the period from weaning to adulthood

The expression and activity of antioxidant enzymes in the liver of rats exposed to high‐fructose diet in the period from weaning to adulthood

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

Molecular mechanisms of lipotoxicity and glucotoxicity in nonalcoholic fatty liver disease

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