Hepatic NPC1L1 overexpression attenuates alcoholic autophagy in mice.

Hepatic NPC1L1 overexpression attenuates alcoholic autophagy in mice. Mol Med Rep. 2019 Aug 01;: Authors: Wang Y, Yang P, Zhang B, Ding Y, Lei S, Hou Y, Guan X, Li Q Abstract Alcohol consumption causes liver steatosis in humans. Metabolic disorders of lipids are one of the factors that cause liver steatosis in hepatocytes. Hepatic Niemann‑Pick C1‑like 1 (NPC1L1) regulates lipid homeostasis in mammals. The relationship between NPC1L1 and autophagy in those with a history of alcohol abuse is unclear. The present study aimed to investigate the function of NPC1L1 in the activation of hepatic autophagy in a mouse model with a human (h)NPC1L1 transgene under alcohol feeding conditions. The mice expressing hNPC1L1 (Ad‑L1) or controls (Ad‑null) were created by retro‑orbital adenovirus injection. The Ad‑L1 and Ad‑null mice were fed with alcohol or a non‑alcoholic diet to mimic chronic alcohol consumption in humans. Hepatic autophagy was demonstrated in isolated primary hepatocytes by monitoring autophagic vacuoles under fluorescence microscopy, and by western blotting for autophagic makers. Isolated hepatocytes from the livers of Ad‑L1 mice were treated with different doses of ezetimibe to study the restoration of autophagy. Chronic alcohol feeding caused liver injury and steatosis, shown by significantly higher levels of plasma alanine transaminase and aspartate transaminase activity, and by hematoxylin and eosin staining in Ad‑L1 and Ad‑nul...
Source: Molecular Medicine Reports - Category: Molecular Biology Tags: Mol Med Rep Source Type: research

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In conclusion, our study demonstrates that IGFBP7 contributes to hepatic steatosis and insulin resistance in NAFLD development, which might serve as a novel therapeutic agent for the treatment of NAFLD. This article is protected by copyright. All rights reserved. PMID: 31397492 [PubMed - as supplied by publisher]
Source: Clinical and Experimental Pharmacology and Physiology - Category: Drugs & Pharmacology Authors: Tags: Clin Exp Pharmacol Physiol Source Type: research
This article is protected by copyright. All rights reserved.
Source: FEBS Letters - Category: Biochemistry Authors: Tags: Research Letter Source Type: research
Mouse Trefoil Factor 3 (Tff3) Ameliorated hepatic steatosis via increasing Peroxisome Proliferator-activated Receptor-α (PPARα) mediated fatty acid oxidation. Am J Physiol Endocrinol Metab. 2019 Jun 18;: Authors: Wu X, Zheng H, Yang R, Luan X, Zhang L, Jin Y, Jin Q, Xue J Abstract Hepatic trefoil factor 3 (Tff3) was identified as a potential protein for the treatment of diabetes, yet the effect of Tff3 on non-alcoholic fatty liver disease (NAFLD) has never been explored. Here, we found that the expression of hepatic Tff3 was significantly decreased in NAFLD mice models, suggesting that Tff...
Source: American Journal of Physiology. Endocrinology and Metabolism - Category: Physiology Authors: Tags: Am J Physiol Endocrinol Metab Source Type: research
In conclusion, TSF improved lipid accumulation and hepatic steatosis by inducing the AMPK/SIRT1 pathway-mediated autophagy. Introduction Nonalcoholic fatty liver disease (NAFLD) has become a worldwide health concern due to the increased incidence of obesity and diabetes. In addition, NAFLD is closely associated with the risk factors of coronary heart disease, such as metabolic syndrome, diabetes mellitus, and dyslipidemia, which are considered to be the leading causes of death (Wiest et al., 2017). Although our understanding of the pathogenesis of NAFLD has significantly improved, there is still no effective medica...
Source: Frontiers in Physiology - Category: Physiology Source Type: research
This article has an associated First Person interview with the first author of the paper.
Source: DMM Disease Models and Mechanisms - Category: Biomedical Science Authors: Tags: Metabolic Disorders RESEARCH ARTICLE Source Type: research
AbstractAdenovirus 5 (Ad-5) infection is a common cause of acute respiratory infections and the main vector used in gene therapy. There are few studies on the relationship of Ad-5 to obesity. In the present study, we evaluated the chronic effects of Ad-5 infection on golden (Syrian) hamsters fed either a balanced diet (BD) or a high-fat diet (HFD). After a single inoculation with Ad-5 (1 × 107 pfu), the body weight of the animals was measured weekly. Medium-term (22 weeks) serum biochemical analyses and long-term (44 weeks) liver morphology, adiposity, and locomotive functionality (movement velocity) assessments were...
Source: Archives of Virology - Category: Virology Source Type: research
We examined the effects of such genes on T2DM using an improved adenovirus vector that demonstrates safer, higher, and longer-term transgene expression than that of the conventional adenovirus vector. We also found that certain foods inhibit the progression of non-alcoholic fatty liver disease, which is related to T2DM. In this review, we introduce our research results, demonstrating how genes and food independently contribute to the mechanisms of T2DM pathology. PMID: 30606928 [PubMed - in process]
Source: Yakugaku Zasshi : Journal of the Pharmaceutical Society of Japan - Category: Drugs & Pharmacology Authors: Tags: Yakugaku Zasshi Source Type: research
Publication date: Available online 15 December 2018Source: Biochimica et Biophysica Acta (BBA) - Molecular Basis of DiseaseAuthor(s): Qinling Pan, Tingfeng Qin, Yuan Gao, Shaojian Li, Danjie Li, Miao Peng, Hening Zhai, Geyang XuAbstractRoux-en-Y Gastric Bypass (RYGB) remains one of the most effective options in treatment of non-alcoholic fatty liver disease (NAFLD). However, the underlying mechanisms are not clear yet. Here, we evaluated the relationship among hepatic mechanistic target of rapamycin (mTOR)-AKT2-insulin-induced gene 2 (Insig2) signaling, lipogenic transcription factors and lipid synthesis enzymes in obese m...
Source: Biochimica et Biophysica Acta (BBA) Molecular Basis of Disease - Category: Molecular Biology Source Type: research
Fight Aging! provides a weekly digest of news and commentary for thousands of subscribers interested in the latest longevity science: progress towards the medical control of aging in order to prevent age-related frailty, suffering, and disease, as well as improvements in the present understanding of what works and what doesn't work when it comes to extending healthy life. Expect to see summaries of recent advances in medical research, news from the scientific community, advocacy and fundraising initiatives to help speed work on the repair and reversal of aging, links to online resources, and much more. This content is...
Source: Fight Aging! - Category: Research Authors: Tags: Newsletters Source Type: blogs
Conclusion: Our present study reveals a critical role of ClC-2 in regulating metabolic diseases. Mice lacking ClC-2 are associated with a remarkably beneficial metabolic phenotype, suggesting that decreasing ClC-2 may be an attractive therapeutic strategy for the treatment of NAFLD.Cell Physiol Biochem 2018;45:2187 –2198
Source: Cellular Physiology and Biochemistry - Category: Cytology Source Type: research
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