ArticleAmerican journal of physiology. Gastrointestinal and liver physiology2015
Chronic NOS inhibition accelerates NAFLD progression in an obese rat model.
Article in American journal of physiology. Gastrointestinal and liver physiology, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 36 citations in OpenAlex.
- Urea cycle dysregulation and arginine pathways in the pathogenesis of NAFLD and NASH (Review).International journal of molecular medicine · 2026Review
- The effects of cannabidiol on nitric oxide synthases: a narrative review on therapeutic implications for inflammation and oxidative stress in health and disease.Journal of cannabis research · 2025Review
- Nitrate containing vegetables and dietary nitrate and nonalcoholic fatty liver disease: a case control study.Nutrition journal · 2023Article
- Exercise-Induced ADAR2 Protects against Nonalcoholic Fatty Liver Disease through miR-34a.Nutrients · 2022Article
- Suppression of nitric oxide synthase aggravates non-alcoholic steatohepatitis and atherosclerosis in SHRSP5/Dmcr rat via acceleration of abnormal lipid metabolism.Pharmacological reports : PR · 2022Article
- Genetics, epigenetics and transgenerational transmission of obesity in children.Frontiers in endocrinology · 2022Review
- Article
- The Emerging Role of Hepatocellular eNOS in Non-alcoholic Fatty Liver Disease Development.Frontiers in physiology · 2020Review
- Allopurinol Prevents the Lipogenic Response Induced by an Acute Oral Fructose Challenge in Short-Term Fructose Fed Rats.Biomolecules · 2019Article
- eNOS deletion impairs mitochondrial quality control and exacerbates Western diet-induced NASH.American journal of physiology. Endocrinology and metabolism · 2019Article
- Oral nitrite restores age-dependent phenotypes in eNOS-null mice.JCI insight · 2018Article
- Early Effects of a Low Fat, Fructose-Rich Diet on Liver Metabolism, Insulin Signaling, and Oxidative Stress in Young and Adult Rats.Frontiers in physiology · 2018Article
- ER Stress Inhibits Liver Fatty Acid Oxidation while Unmitigated Stress Leads to Anorexia-Induced Lipolysis and Both Liver and Kidney Steatosis.Cell reports · 2017Article
- Ablation of eNOS does not promote adipose tissue inflammation.American journal of physiology. Regulatory, integrative and comparative physiology · 2016Article
- Identification of cysteinylated transthyretin, a predictive biomarker of treatment response to partially hydrolyzed guar gum in type 2 diabetes rats, by surface-enhanced laser desorption/ionization time-of-flight mass spectrometry.Journal of clinical biochemistry and nutrition · 2016Article
- Deficiency of eNOS exacerbates early-stage NAFLD pathogenesis by changing the fat distribution.BMC gastroenterology · 2015Article
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Authors and funding
5 authors at 3 institutions in 1 country.
Funding
Abstract
The progression in nonalcoholic fatty liver disease (NAFLD) to nonalcoholic steatohepatitis is a serious health concern, but the underlying mechanisms remain unclear. We hypothesized that chronic inhibition of nitric oxide (NO) synthase (NOS) via N(ω)-nitro-L-arginine methyl ester (L-NAME) would intensify liver injury in a rat model of obesity, insulin resistance, and NAFLD. Obese Otsuka Long-Evans Tokushima fatty (OLETF) and lean Long-Evans Tokushima Otsuka (LETO) rats received control or L-NAME (65-70 mg·kg(-1)·day(-1))-containing drinking water for 4 wk. L-NAME treatment significantly (P < 0.05) reduced serum NO metabolites and food intake in both groups. Remarkably, despite no increase in body weight, L-NAME treatment increased hepatic triacylglycerol content (+40%, P < 0.05) vs. control OLETF rats. This increase was associated with impaired (P < 0.05) hepatic mitochondrial state 3 respiration. Interestingly, the opposite effect was found in LETO rats, where L-NAME increased (P < 0.05) hepatic mitochondrial state 3 respiration. In addition, L-NAME induced a shift toward proinflammatory M1 macrophage polarity, as indicated by elevated hepatic CD11c (P < 0.05) and IL-1β (P = 0.07) mRNA in OLETF rats and reduced expression of the anti-inflammatory M2 markers CD163 and CD206 (P < 0.05) in LETO rats. Markers of total macrophage content (CD68 and F4/80) mRNA were unaffected by L-NAME in either group. In conclusion, systemic NOS inhibition in the obese OLETF rats reduced hepatic mitochondrial respiration, increased hepatic triacylglycerol accumulation, and increased hepatic inflammation. These findings suggest an important role for proper NO metabolism in the hepatic adaptation to obesity.
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