High circulatory leptin mediated NOX-2-peroxynitrite-miR21 axis activate mesangial cells and promotes renal inflammatory pathology in nonalcoholic fatty liver disease

Publication date: July 2018Source: Redox Biology, Volume 17Author(s): Firas Alhasson, Ratanesh Kumar Seth, Sutapa Sarkar, Diana A. Kimono, Muayad S. Albadrani, Diptadip Dattaroy, Varun Chandrashekaran, Geoffrey I. Scott, Samir Raychoudhury, Mitzi Nagarkatti, Prakash Nagarkatti, Anna Mae Diehl, Saurabh ChatterjeeAbstractHigh circulatory insulin and leptin followed by underlying inflammation are often ascribed to the ectopic manifestations in non-alcoholic fatty liver disease (NAFLD) but the exact molecular pathways remain unclear. We have shown previously that CYP2E1-mediated oxidative stress and circulating leptin in NAFLD is associated with renal disease severity. Extending the studies, we hypothesized that high circulatory leptin in NAFLD causes renal mesangial cell activation and tubular inflammation via a NOX2 dependent pathway that upregulates proinflammatory miR21. High-fat diet (60% kcal) was used to induce fatty liver phenotype with parallel insulin and leptin resistance. The kidneys were probed for mesangial cell activation and tubular inflammation that showed accelerated NASH phenotype and oxidative stress in the liver. Results showed that NAFLD kidneys had significant increases in α-SMA, a marker of mesangial cell activation, miR21 levels, tyrosine nitration and renal inflammation while they were significantly decreased in leptin and p47 phox knockout mice. Micro RNA21 knockout mice showed decreased tubular immunotoxicity and proinflammatory mediator releas...
Source: Redox Biology - Category: Biology Source Type: research

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AbstractPurpose of ReviewNon-alcoholic fatty liver disease (NAFLD) is the most common chronic liver disease in the USA, affecting over 7 million children. In this article, we provide an update on pediatric NAFLD by briefly reviewing the recent publications in diagnosis, screening, therapy, and follow-up.Recent FindingsNAFLD remains a diagnosis of exclusion and liver biopsy is the most accurate test to assess severity of the disease in children. There is a growing collection of studies testing noninvasive tests for hepatic steatosis and fibrosis, several of which have become available in more recent years, such as fibrosis ...
Source: Current Hepatitis Reports - Category: Infectious Diseases Source Type: research
TUESDAY, Oct. 16, 2018 -- Web-based programs may be effective in helping patients make lifestyle changes to control non-alcoholic fatty liver disease (NAFLD), according to a study published in the November issue of the Journal of Hepatology. Arianna...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
Conclusions: Non-obese patients present a substantial proportion of pediatric NAFLD cases. Significant abnormal lipid concentrations were found in non-obese and abdominal obesity was important risk factor for non-obese NAFLD. PMID: 30304905 [PubMed - as supplied by publisher]
Source: Korean Journal of Pediatrics - Category: Pediatrics Tags: Korean J Pediatr Source Type: research
FRIDAY, Oct. 12, 2018 -- For patients with nonalcoholic fatty liver disease (NAFLD), modest alcohol consumption is associated with a reduction in all-cause mortality, while drinking 1.5 or more drinks per day may increase mortality, according to a...
Source: Drugs.com - Pharma News - Category: Pharmaceuticals Source Type: news
Abstract Non-alcoholic fatty liver disease (NAFLD) medication is an unmet need. Glucocorticoid stress hormones (GC) drive fat metabolism in the liver, but both full blockade and full stimulation of GC signaling aggravate NAFLD pathology. We investigated the efficacy of selective glucocorticoid receptor (GR) modulator CORT118335, that recapitulates only a subset of GC actions, in reducing liver lipid accumulation in mice. Male C57BL/6J mice received low-fat diet, or high-fat diet mixed with vehicle or CORT118335. Livers were analyzed histologically and for genome-wide mRNA expression. Functionally, hepatic long-cha...
Source: Endocrinology - Category: Endocrinology Authors: Tags: Endocrinology Source Type: research
Authors: Nakamura M, Eguchi A, Inohana M, Nagahara R, Murayama H, Kawashima M, Mizukami S, Koyanagi M, Hayashi SM, Maronpot RR, Shibutani M, Yoshida T Abstract Mineralocorticoid receptor (MR)/NADPH oxidase (NOX) signaling is involved in the development of obesity, insulin resistance, and renal diseases; however, the role of this signaling on steatotic preneoplastic liver lesions is not fully elucidated. We determined the effects of the MR antagonist potassium canrenoate (PC) on MR/NOX signaling in hepatic steatosis and preneoplastic glutathione S-transferase placental form (GST-P)-positive liver foci. Rats were sub...
Source: Journal of Toxicological Sciences - Category: Toxicology Tags: J Toxicol Sci Source Type: research
CONCLUSION: - In post-menopausal women with T2DM, the presence of NAFLD and significant fibrosis was associated with a low bone turnover, which may reflect the presence of qualitative bone abnormalities. PMID: 30315891 [PubMed - as supplied by publisher]
Source: Diabetes and Metabolism - Category: Endocrinology Authors: Tags: Diabetes Metab Source Type: research
AbstractNon-alcoholic fatty-liver disease (NAFLD) is now considered one of the leading causes of liver disease worldwide and is associated with metabolic syndrome and obesity. There are several factors contributing to the disease state. Recent research suggests that the intestinal microbiota (IM) and bacterial products may play a role through several mechanisms which include increased energy uptake, intestinal permeability and chronic inflammation. In addition to diet and exercise, treatment options targeting the IM are being investigated and include the use of pre-, pro- and synbiotics as well as the possibility of fecal ...
Source: European Journal of Nutrition - Category: Nutrition Source Type: research
Lysosomal Acid Lipase Deficiency (LAL-D) is an autosomal recessive disorder caused by mutations in LIPA that manifests as a spectrum of liver disease and dyslipidaemia[1,2]. It is regarded as a rare disorder however recognition of more mild forms of the condition have led to the suggestions that it may represent a significant proportion of patients presenting with non-alcoholic fatty liver disease (NAFLD)[3,4]. Emerging data have also reported reduced lysosomal acid lipase (LAL) activity in association with more advanced NAFLD[5 –8].
Source: Journal of Hepatology - Category: Gastroenterology Authors: Source Type: research
Weight loss by lifestyle modification is the cornerstone therapy of Non Alcoholic Fatty Liver Disease. Low carbohydrate diet has showed favorable effects for body weight as well as hepatic fat content in several reports. In this meta-analysis, we review clinical studies article to date regarding the composition of the diet and analyzed the impact of low carbohydrate diet comparing to low calorie diet on hepatic fat change, AST and ALT using Forest plot. We aimed to investigate the efficacy of low carbohydrate diet on NAFLD.
Source: Clinical Nutrition - Category: Nutrition Authors: Tags: Meta-analyses Source Type: research
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