ArticleJournal of applied physiology (Bethesda, Md. : 1985)2014
Reduced hepatic eNOS phosphorylation is associated with NAFLD and type 2 diabetes progression and is prevented by daily exercise in hyperphagic OLETF rats.
Article in Journal of applied physiology (Bethesda, Md. : 1985), 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 29 citations in OpenAlex.
- Inhibition of hepatic gluconeogenesis in type 2 diabetes by metformin: complementary role of nitric oxide.Medical gas research · 2025Review
- Exercise duration and detraining influence not only body weight but also histopathological changes in the white adipose tissue of young male OLETF rats as an obesity model.Physiological reports · 2025Article
- Mitochondrial metabolic dysfunction and non-alcoholic fatty liver disease: new insights from pathogenic mechanisms to clinically targeted therapy.Journal of translational medicine · 2023Review
- Hepatocyte-specific eNOS deletion impairs exercise-induced adaptations in hepatic mitochondrial function and autophagy.Obesity (Silver Spring, Md.) · 2022Article
- Alpinetin: A Review of Its Pharmacology and Pharmacokinetics.Frontiers in pharmacology · 2022Review
- Article
- Four weeks exercise training enhanced the hepatic insulin sensitivity in high fat- and high carbohydrate-diet fed hyperinsulinemic rats.Journal of diabetes and metabolic disorders · 2020Article
- The Emerging Role of Hepatocellular eNOS in Non-alcoholic Fatty Liver Disease Development.Frontiers in physiology · 2020Review
- eNOS deletion impairs mitochondrial quality control and exacerbates Western diet-induced NASH.American journal of physiology. Endocrinology and metabolism · 2019Article
- Integrative omics analysis identifies macrophage migration inhibitory factor signaling pathways underlying human hepatic fibrogenesis and fibrosis.Journal of bio-X research · 2019Article
- Endothelial function does not improve with high-intensity continuous exercise training in SHR: implications of eNOS uncoupling.Hypertension research : official journal of the Japanese Society of Hypertension · 2016Article
- A Combination of Leucine, Metformin, and Sildenafil Treats Nonalcoholic Fatty Liver Disease and Steatohepatitis in Mice.International journal of hepatology · 2016Article
- Chronic NOS inhibition accelerates NAFLD progression in an obese rat model.American journal of physiology. Gastrointestinal and liver physiology · 2015Article
- Pathogenesis and Prevention of Hepatic Steatosis.Gastroenterology & hepatology · 2015Article
- Voluntary Exercise Can Ameliorate Insulin Resistance by Reducing iNOS-Mediated S-Nitrosylation of Akt in the Liver in Obese Rats.PloS one · 2015Article
- Acute liver injury induced by low dose dimethylnitrosamine alters mediators of hepatic vascular flow.Toxicology reports · 2014Article
- Pathophysiological Features of Rat Models of Nonalcoholic Fatty Liver Disease/Nonalcoholic Steatohepatitis.In vivo (Athens, Greece)Review
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
We tested the hypothesis that nonalcoholic fatty liver disease (NAFLD) is associated with reduced hepatic endothelial nitric oxide synthase (eNOS) activation status via S1177 phosphorylation (p-eNOS) and is prevented by daily voluntary wheel running (VWR). Hyperphagic Otsuka Long-Evans Tokushima Fatty (OLETF) rats, an established model of obesity, type 2 diabetes (T2D) and NAFLD, and normophagic controls [Long-Evans Tokushima Otsuka (LETO)] were studied at 8, 20, and 40 wk of age. Basal hepatic eNOS phosphorylation (p-eNOS/eNOS) was similar between LETO and OLETFs with early hepatic steatosis (8 wk of age) and advanced steatosis, hyperinsulinemia, and hyperglycemia (20 wk of age). In contrast, hepatic p-eNOS/eNOS was significantly lower (P < 0.05) in OLETF rats with T2D advancement and the transition to more advanced NAFLD with inflammation and fibrosis [increased tumor necrosis factor-α (TNF-α), CD68, and CD163 mRNA expression; 40 wk of age]. Reduced hepatic eNOS activation status in 40-wk OLETF rats was significantly correlated with reduced p-Akt/Akt (r = 0.73, P < 0.05), reduced serum insulin (r = 0.59, P < 0.05), and elevated serum glucose (r = -0.78, P < 0.05), suggesting a link between impaired glycemic control and altered hepatic nitric oxide metabolism. VWR by OLETF rats, in conjunction with NAFLD and T2D prevention, normalized p-eNOS/eNOS and p-Akt/Akt to LETO levels. Basal activation of hepatic eNOS and Akt are maintained until advanced NAFLD and T2D development in obese OLETF rats. The prevention of this reduction by VWR may result from maintained insulin sensitivity and glycemic control.
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