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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CONCLUSIONS: NALFD can lead to a reduction in the hepatic CLint of a drug if it is a substrate of the CYP2D subfamily. The decreased clearance may result in elevated drug concentrations and increased exposure. PMID: 30786957 [PubMed - in process]
Source: J Pharm Pharm Sci - Category: Drugs & Pharmacology Authors: Tags: J Pharm Pharm Sci Source Type: research
Condition:   Non Alcoholic Fatty Liver Disease Interventions:   Dietary Supplement: Niacinamide Oral Tablet;   Drug: Antidiabetic Sponsor:   Ain Shams University Recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
In conclusion, application of immunohistochemical markers of hepatocyte injury may serve as a more objective tool for distinguishing NASH from NAFL, facilitating improved resolution of hepatic molecular changes associated with progression of NAFLD.
Source: GEO: Gene Expression Omnibus - Category: Genetics & Stem Cells Tags: Expression profiling by high throughput sequencing Homo sapiens Source Type: research
ConclusionIn conclusion, the present trial shows that supplementation with a phytosomal preparation of curcumin containing phosphatidylserine and piperine could improve glycemic factors, hepatic function and serum cortisol levels in subjects with overweight and impaired fasting glucose.
Source: European Journal of Nutrition - Category: Nutrition Source Type: research
Inhibition of Soluble Epoxide Hydrolase Ameliorates Hyperhomocysteinemia-Induced Hepatic Steatosis by Enhancing β-oxidation of Fatty Acid in Mice. Am J Physiol Gastrointest Liver Physiol. 2019 Feb 21;: Authors: Yao L, Cao B, Cheng Q, Cai W, Ye C, Liang J, Liu W, Tan L, Yan M, Li B, He J, Hwang SH, Zhang X, Wang C, Ai D, Hammock BD, Zhu Y Abstract Hepatic steatosis is the beginning phase of non-alcoholic fatty liver disease, and hyperhomocysteinemia (HHcy) is a significant risk factor. Soluble epoxide hydrolase (sEH) hydrolyzes epoxyeicosatrienoic acids (EETs) and other epoxy fatty acids, attenuat...
Source: Am J Physiol Gastroi... - Category: Gastroenterology Authors: Tags: Am J Physiol Gastrointest Liver Physiol Source Type: research
Conditions:   NAFLD;   Smoking;   Alcohol Consumption;   Bone Mineral Density Intervention:   Sponsor:   Ningbo No. 1 Hospital Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Non-Alcoholic Fatty Liver Disease Interventions:   Behavioral: Conventional diet;   Behavioral: Modified Time-restricted Feeding;   Behavioral: Physical activity;   Behavioral: Restricted consumption of sweetened beverages Sponsor:   The University of Texas Health Science Center, Houston Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   NAFLD;   Smoking;   Alcohol Consumption;   Bone Mineral Density Intervention:   Sponsor:   Ningbo No. 1 Hospital Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Condition:   Non-Alcoholic Fatty Liver Disease Interventions:   Behavioral: Conventional diet;   Behavioral: Modified Time-restricted Feeding;   Behavioral: Physical activity;   Behavioral: Restricted consumption of sweetened beverages Sponsor:   The University of Texas Health Science Center, Houston Not yet recruiting
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
Conditions:   NAFLD;   Smoking;   Alcohol Consumption;   Bone Mineral Density Intervention:   Sponsor:   Ningbo No. 1 Hospital Completed
Source: ClinicalTrials.gov - Category: Research Source Type: clinical trials
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