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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This study aimed to investigate the role of CXC chemokine ligand 16 (CXCL16) and its receptor CXC chemokine receptor 6 (CXCR6) in NAFLD under inflammation. We used IL-1β stimulation in human hepatoblastoma cell line (HepG2) for in vitro studies and casein injection in apolipoprotein E knockout mice in vivo to induce inflammatory stress. The effects of inflammation on cholesterol accumulation were examined by histochemical staining and a quantitative intracellular cholesterol assay. The gene and protein expression of molecules involved in CXCL16/CXCR6 pathway and extracellular matrix (ECM) were examined by real-time po...
Source: American Journal of Translational Research - Category: Research Tags: Am J Transl Res Source Type: research
This study aimed to explore the direct association of NAFLD with thyroid autoimmune disease (AITD) among participants with normal thyroid stimulating hormone (TSH) levels. The data were obtained from a cross-sectional study (SPECT-China). A total of 7982 participants were enrolled. Participants underwent several checkups including peroxidase antibody (TPOAb), thyroglobulin antibody (TgAb), thyroid, and liver ultrasonography (US). The prevalence of NAFLD was higher in TPOAb and/or TgAb positive [TPO/TgAb (+)] group and TPOAb and/or TgAb together with US positive [TPO/TgAb (+) and US (+)] group for both genders. After full a...
Source: Autoimmunity - Category: Allergy & Immunology Tags: Autoimmunity Source Type: research
Authors: Polyzos SA, Margioris AN Abstract Sarcopenic obesity, a chronic condition, is today a major public health problem with increasing prevalence worldwide, which is due to progressively aging populations, the increasing prevalence of obesity, and the changes in lifestyle during the last several decades. Patients usually present to healthcare facilities for obesity and related comorbidities (type 2 diabetes mellitus, non-alcoholic fatty liver disease, dyslipidemia, hypertension, and cardiovascular disease) or for non-specific symptoms related to sarcopenia per se (e.g., fatigue, weakness, and frailty). Because ...
Source: Hormones - Category: Endocrinology Tags: Hormones (Athens) Source Type: research
In this study, we have re‐examined the predictive value of these serum microRNAs and found that only 6 of them (miR‐34a, ‐192, ‐27b, ‐122, ‐197 and ‐30c) are validated in our independent cohort as biomarkers associated with NAFLD severity. Among them, miR‐192, ‐27b and ‐122 are abundantly expressed in liver and confidently detected in serum, and display strong correlations with transaminases. The classification performance of validated miRNAs (and their ratios) for patients with non‐alcoholic steatohepatitis (NASH) is similar to that reached by AST, whereas f or advanced fibrosis prediction, the miR...
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Non-coding RNA profiling by high throughput sequencing Homo sapiens Source Type: research
This study aimed to identify circulating miRNAs for early diagnosis of the complication.Materials and methodsPlasma miRNA expression profiles of T2DM patients complicated with or without NAFLD were examined by miRNA array analysis and then were validated by qRT-PCR. A new index for prediction the presence of NAFLD was developed based on the result of multivariate logistic regression analysis. STZ and high fat diet were used for construction a rat model of T2DM complicated with NAFLD.Key findingsPlasma miR-17, miR-20a, miR-20b, and miR-122 were up-regulated in T2DM patients with NAFLD complicated compared in those without NAFLD (P 
Source: Life Sciences - Category: Biology Source Type: research
Liver International,Volume 0, Issue ja, -Not available-.
Source: Liver International - Category: Gastroenterology Authors: Source Type: research
Publication date: Available online 17 July 2018Source: Pharmacological ResearchAuthor(s): Stefano Fiorucci, Michele Biagioli, Eleonora DistruttiAbstractWith an estimated prevalence of ≈25% in Western and Asian countries, non alcoholic fatty liver disease (NAFLD), caused by chronic excessive caloric intake, is the emerging as the most prevalent liver disorder worldwide. NAFLD exists in two clinical entities, non-alcoholic fatty liver disease (NAFL), a relative benign disease that carry on minimal risk of liver-related morbidity but significant risk of cardiovascular complications, and non-alcoholic steatohepatitis (NA...
Source: Pharmacological Research - Category: Drugs & Pharmacology Source Type: research
ConclusionThese results suggest that LLE may exert protective effects against NAFLD-related obesity and metabolic disease.Graphical abstract
Source: Phytomedicine - Category: Drugs & Pharmacology Source Type: research
CONCLUSIONS: HFD, HFruD, and HFHF developed morphologic hepatic changes ranging from steatosis to necrosis and inflammation, besides the development of internal metabolic impairments. The chief factors of hepatic injury were fat accumulation in the hepatocytes, oxidative stress and highly elevated iNOS. Compared to the other groups, HFHF's effect was more prominent. PMID: 30009361 [PubMed - as supplied by publisher]
Source: Folia Morphologica - Category: Anatomy Tags: Folia Morphol (Warsz) Source Type: research
Source: BMJ Comments - Category: General Medicine Source Type: forums
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