- Metformin-Induced Changes of the Coding Transcriptome and Non-Coding RNAs in the Livers of Non-Alcoholic Fatty Liver Disease Mice. [Journal Article]
- CPCell Physiol Biochem 2018 Feb 16; 45(4):1487-1505
- CONCLUSIONS: The present study identified novel changes in the coding transcriptome and non-coding RNAs in the livers of NAFLD mice after metformin treatment that might shed light on the underlying mechanism by which metformin impedes the progression of NAFLD.
- Family history and obesity in youth, their effect on acylcarnitine/aminoacids metabolomics and non-alcoholic fatty liver disease (NAFLD). Structural equation modeling approach. [Journal Article]
- PlosPLoS One 2018; 13(2):e0193138
- CONCLUSIONS: Family history of obesity is the major predictor of obesity, and the metabolic abnormalities on amino acids, acylcarnitines, inflammation, insulin resistance, and NAFLD.
- Effects of combined therapy with resveratrol, continuous and interval exercises on apoptosis, oxidative stress, and inflammatory biomarkers in the liver of old rats with non-alcoholic fatty liver disease. [Journal Article]
- APArch Physiol Biochem 2018 Feb 20; :1-8
- CONCLUSIONS: Although resveratrol alone has an antioxidant, anti-apoptotic and anti-inflammatory properties, combined therapy with interval, and continuous training can be more effective to mitigate these abnormalities in NAFLD patients.
- The Nile Rat (Arvicanthis niloticus) as a Superior Carbohydrate-Sensitive Model for Type 2 Diabetes Mellitus (T2DM). [Review]
- NNutrients 2018 Feb 18; 10(2)
- Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complicati...
Type II diabetes mellitus (T2DM) is a multifactorial disease involving complex genetic and environmental interactions. No single animal model has so far mirrored all the characteristics or complications of diabetes in humans. Since this disease represents a chronic nutritional insult based on a diet bearing a high glycemic load, the ideal model should recapitulate the underlying dietary issues. Most rodent models have three shortcomings: (1) they are genetically or chemically modified to produce diabetes; (2) unlike humans, most require high-fat feeding; (3) and they take too long to develop diabetes. By contrast, Nile rats develop diabetes rapidly (8-10 weeks) with high-carbohydrate (hiCHO) diets, similar to humans, and are protected by high fat (with low glycemic load) intake. This review describes diabetes progression in the Nile rat, including various aspects of breeding, feeding, and handling for best experimental outcomes. The diabetes is characterized by a strikinggenetic permissivenessinfluencing hyperphagia and hyperinsulinemia; random blood glucose is the best index of disease progression; and kidney failure with chronic morbidity and death are outcomes, all of which mimic uncontrolled T2DM in humans. Non-alcoholic fatty liver disease (NAFLD), also described in diabetic humans, results from hepatic triglyceride and cholesterol accumulation associated with rising blood glucose. Protection is afforded by low glycemic load diets rich in certain fibers or polyphenols. Accordingly, the Nile rat provides a unique opportunity to identify the nutritional factors and underlying genetic and molecular mechanisms that characterize human T2DM.
- Non-alcoholic Fatty Liver Disease and Gastric Bypass Surgery Regulate Serum And Hepatic Levels of Pyruvate Kinase Isoenzyme M2. [Journal Article]
- AJAm J Physiol Endocrinol Metab 2018 Feb 20
- Treatment of non-alcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents ...
Treatment of non-alcoholic fatty liver disease (NAFLD) focuses on the underlying metabolic syndrome, and Roux-en-Y gastric bypass surgery (RYGB) remains one of the most effective options. In rodents and human patients, RYGB induces an increase in the gene and protein expression levels of the M2 isoenzyme of Pyruvate Kinase (PKM2) in the jejunum. Since PKM2 can be secreted in the circulation, our hypothesis was that the circulating levels of PKM2 increase after RYGB. Our data, however, revealed an unexpected finding and a potential new role of PKM2 for the natural history of metabolic syndrome and NAFLD. Contrary to our initial hypothesis, RYGB-treated patients had decreased PKM2 blood levels compared to a well-matched group of patients with severe obesity prior to RYGB. Interestingly, PKM2 serum concentration correlated with BMI before but not after the surgery. This prompted us to evaluate other potential mechanisms and sites of PKM2 regulation by the metabolic syndrome and RYGB. We found that in patients with NAFLD and NASH, the liver had increased PKM2 expression levels, and the enzyme appears to be specifically localized in Kupffer cells. The study of murine models of metabolic syndrome and NASH replicated this pattern of expression, further suggesting a metabolic link between hepatic PKM2 and NAFLD. Therefore, we conclude that PKM2 serum and hepatic levels increase in both metabolic syndrome and NAFLD and decrease after RYGB. Thus, PKM2 may represent a new target for monitoring and treatment of NAFLD.
- PycnogenolRprotects against diet-induced hepatic steatosis in Apolipoprotein-E deficient mice. [Journal Article]
- AJAm J Physiol Endocrinol Metab 2018 Feb 20
- Pycnogenol (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial...
Pycnogenol (PYC), a combination of active flavonoids derived from French maritime pine bark, is a natural antioxidant that has various pharmacological activities. Here, we investigated the beneficial effect of PYC on diet-induced hepatic steatosis. Apolipoprotein E (ApoE)-deficient male mice were administered PYC at oral doses of 30 or 100 mg•kg-1 •day-1 for two weeks in advance and were then fed a high cholesterol and fat diet (HCD) for eight weeks. Biochemical, immunohistochemical, and gene expression analyses were conducted to explore the effect of PYC on lipid metabolism in ApoE-deficient mice on a HCD. Short-term treatment with HCD in ApoE-deficient mice induced hepatic injuries, such as lipid metabolism disorder and hepatic histopathological changes. We found that PYC reduced body weight and the increase of serum lipids that had been caused by HCD. Supplementation of PYC significantly reduced lipid deposition in the liver, as shown by the lowered hepatic lipid content and histopathological lesions. We subsequently detected genes related to lipid metabolism and inflammatory cytokines. The study showed that PYC markedly suppressed the expression of genes related to hepatic lipogenesis, fatty acid uptake, and lipid storage while increasing the lipolytic gene, which thus reduced hepatic lipid content. Furthermore, PYC mainly reduced the expression of inflammatory cytokines and the infiltration of inflammatory cells, which were resistant to the development of hepatic steatosis. These results demonstrate that PYC protects against the occurrence and development of hepatic steatosis and may provide a new prophylactic approach for non-alcoholic fatty liver disease (NAFLD).
- FEATURES OF EXCRETION OF MELATONIN IN URINE IN PATIENTS WITH TYPE 2 DIABETES MELLITUS AND NON-ALCOHOLIC FATTY LIVER DISEASE WITH MANIFESTATIONS OF FIBROSIS AND ITS RELATIONSHIP WITH CERTAIN METABOLIC AND IMMUNOLOGICAL INDICATORS. [Journal Article]
- GMGeorgian Med News 2018; (274):103-107
- To study the features of secretion of melatonin in the urine in patients with DM type 2 and NAFLD with manifestations of fibrosis and its relationship with some metabolic and immunological parameters...
To study the features of secretion of melatonin in the urine in patients with DM type 2 and NAFLD with manifestations of fibrosis and its relationship with some metabolic and immunological parameters, 23 patients with DM type 2 and NAFLD were examined. The degree of fibrosis in patients was diagnosed on the basis of static elastography and the study of indirect fibrosis markers 16 persons (72%) diagnosed with mild fibrosis (F0-F1 on METAVIR), 5 people (18.2%) - with moderate fibrosis (F2-F3 on METAVIR). Only 2 (8.7%) patients did not have any fibrotic disorders, so they were excluded from the further study. All patients underwent determination of melatonin excretion of albumin and in daily urine, as well as the determination of homocysteine in the blood. The level of excretion of melatonin in the urine in patients with DM type 2 and NAFLD did not depend on the degree of fibrosis and on the average was 89.50±16.66 mmol/day, which exceeded the reference values. It has been established that the increase in melatonin level in patients with DM type 2 and NAFLD is associated with the presence of fibrotic changes in the liver and a decrease in the activity of the inflammatory process. In addition, a direct correlation was found between the excretion of melatonin and homocysteine (r=0.43), as well as between melatonin and albumin excretion in the urine (r=0.20). Thus, an increased level of excretion of melatonin in the urine can be not only a marker of liver fibrosis, but also a predictor of cardiovascular disorders in patients with DM type 2 and NAFLD.
- Nonylphenol aggravates non-alcoholic fatty liver disease in high sucrose-high fat diet-treated rats. [Journal Article]
- SRSci Rep 2018 Feb 19; 8(1):3232
- Exposure to environmental endocrine disruptors (EEDs) contributes to the pathogenesis of many metabolic disorders. Here, we have analyzed the effect of the EED-nonylphenol (NP) on the promotion of no...
Exposure to environmental endocrine disruptors (EEDs) contributes to the pathogenesis of many metabolic disorders. Here, we have analyzed the effect of the EED-nonylphenol (NP) on the promotion of non-alcoholic fatty liver disease (NAFLD) in rats fed high sucrose-high fat diet (HSHFD). Fifty Sprague-Dawley rats were divided into five groups: controls fed a normal diet (C-ND); HSHFD-fed controls (C-HSHFD); and rats fed a HSHFD combined with NP at doses of 0.02 μg/kg/day (NP-L-HSHFD), 0.2 μg/kg/day (NP-M-HSHFD), and 2 μg/kg/day (NP-H-HSHFD). Subchronic exposure to NP coupled with HSHFD increased daily water and food intake (p < 0.05), hepatic echogenicity and oblique liver diameter (p < 0.05), and plasma levels of alanine aminotransferase, aspartate aminotransferase, total cholesterol, triglycerides, and low density lipoprotein cholesterol (p < 0.05). Combined exposure to NP and HSHFD induced macrovesicular steatosis with dilation and congestion of the central vein, liver inflammatory cell infiltration, and expression of genes regulating lipid metabolism, SREBP-1C, FAS, and Ucp2. These results demonstrate that NP aggravates NAFLD in HSHFD-treated rats by up-regulating lipogenic genes, and that HSHFD increases the toxic effects of NP. Thus subchronic NP exposure may lead to NAFLD, especially when combined with a high-sucrose/high-fat diet.
- Bax Inhibitor-1 protects from Non-Alcoholic Steatohepatitis by limiting IRE1α signaling. [Journal Article]
- HepHepatology 2018 Feb 19
- CONCLUSIONS: Targeting IRE1α-dependent NLRP3 inflammasome signaling with pharmacological agents or via BI-1 may represent a tangible therapeutic strategy for NASH. This article is protected by copyright. All rights reserved.
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- DEPTOR Suppresses Lipogenesis and Ameliorates Hepatic Steatosis and Acute-on-Chronic Liver Injury in Alcoholic Liver Disease. [Journal Article]
- HepHepatology 2018 Feb 19
- CONCLUSIONS: the dysregulation of SIRT1-DEPTOR-mTORC1 signaling is a critical determinant of ALD pathology. Targeting SIRT1 and DEPTOR and selectively inhibiting mTORC1-S6K1 signaling may have therapeutic potential for treating ALD in humans. This article is protected by copyright. All rights reserved.