ArticlePloS one2018
CB1 receptor blockade ameliorates hepatic fat infiltration and inflammation and increases Nrf2-AMPK pathway in a rat model of severely uncontrolled diabetes.
Article in PloS one, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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Who cites it
22 citing papers in PubMed, 37 citations in OpenAlex.
- Beyond energy balance: 2-arachidonoylglycerol at the crossroads of obesity, inflammation, and metabolic dysfunction.Molecular biology reports · 2026Review
- Hepatic CB1 receptor signaling triggers GMetabolism: clinical and experimental · 2025Article
- Cannabinoid Receptors CB1 and CB2 Activation Restores Hippocampal Lipid Profiles and Alleviates Autism-Like Behaviors in Valproic Acid-Induced ASD Rats.CNS neuroscience & therapeutics · 2025Article
- Effects of five cannabis oils with different CBD: THC ratios and terpenes on hypertension, dyslipidemia, hepatic steatosis, oxidative stress, and CB1 receptor in an experimental model.Journal of cannabis research · 2025Article
- Ezetimibe, Niemann-Pick C1 like 1 inhibitor, modulates hepatic phospholipid metabolism to alleviate fat accumulation.Frontiers in pharmacology · 2024Article
- Regulation of Intestinal Flora and Immune Response by Cyanidin Exhibits Protective Effect against Type-2 Diabetes in Rat Model.Doklady. Biochemistry and biophysics · 2023Article
- Effects of the CB1 receptor antagonists AM6545 and AM4113 on metabolic syndrome-induced prostatic hyperplasia in rats.Biomolecules & biomedicine · 2023Article
- Krill oil inhibited adipogenic differentiation by inducing the nuclear Nrf2 expression and the AMPK activity.Food science & nutrition · 2023Article
- Expanding Research on Cannabis-Based Medicines for Liver Steatosis: A Low-Risk High-Reward Way Out of the Present Deadlock?Cannabis and cannabinoid research · 2023Article
- Blockade of CB1 or Activation of CB2 Cannabinoid Receptors Is Differentially Efficacious in the Treatment of the Early Pathological Events in Streptozotocin-Induced Diabetic Rats.International journal of molecular sciences · 2022Article
- The Endocannabinoid System and Physical Activity-A Robust Duo in the Novel Therapeutic Approach against Metabolic Disorders.International journal of molecular sciences · 2022Review
- Potential Implications of Rimonabant on Age-Related Oxidative Stress and Inflammation.Antioxidants (Basel, Switzerland) · 2022Article
- Rho-Kinase as a Therapeutic Target for Nonalcoholic Fatty Liver Diseases.Diabetes & metabolism journal · 2021Review
- miR‑875‑5p regulates IR and inflammation via targeting TXNRD1 in gestational diabetes rats.Molecular medicine reports · 2021Article
- Transplantation of brown adipose tissue up-regulates miR-99a to ameliorate liver metabolic disorders in diabetic mice by targeting NOX4.Adipocyte · 2020Article
- Cannabinoids in Metabolic Syndrome and Cardiac Fibrosis.Current hypertension reports · 2020Review
- Targeting the Endocannabinoid CB1 Receptor to Treat Body Weight Disorders: A Preclinical and Clinical Review of the Therapeutic Potential of Past and Present CB1 Drugs.Biomolecules · 2020Review
- A Guide to Targeting the Endocannabinoid System in Drug Design.International journal of molecular sciences · 2020Review
- Novel CB1 receptor antagonist BAR-1 modifies pancreatic islet function and clinical parameters in prediabetic and diabetic mice.Nutrition & diabetes · 2020Article
- Obesity Affects the Microbiota-Gut-Brain Axis and the Regulation Thereof by Endocannabinoids and Related Mediators.International journal of molecular sciences · 2020Review
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Authors and funding
6 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Previous studies have shown that the CB1 receptor antagonist reverses steatohepatitis and its related features of metabolic syndrome, such as obesity and type 2 diabetes. However, the beneficial effects of CB1 receptor blockade on hepatic steatosis and inflammation have not been investigated independently of its effects on body weight and glycemic control. At 32 weeks of age, OLETF rats were administered with rimonabant (10 mg·kg-1·day-1) by oral gavage for 6 weeks. No significant changes in body weight, OGTT, and serum glucose were observed in spite of rimonabant-decreased food intake. Moreover, there was a significant difference between initial and final body weight, regardless of rimonabant administration, indicating that OLETF rats were severely diabetic rats. Rimonabant administration significantly decreased serum liver enzyme levels such as ALT and AST, hepatic fat accumulation, lipid peroxidation, and cell death as demonstrated by the number of TUNEL-positive cells in severely uncontrolled diabetic OLETF rats. Significant decreases in hepatic gene expression of proinflammatory cytokines (CD11b, F4/80, MCP1, and TNFα), negative inflammatory mediators (SOCS1 and SOCS3), and fibrosis-related proteins (TGFβ, collagen 1, and TIMP1) were found in rimonabant-treated OLETF rats. Six-week administration of rimonabant significantly upregulated mRNA levels of CPT1α and PPARα related to β-oxidation. Moreover, significant increases in Nrf2 gene expression and its downstream genes, NQO1, GSAT, HO-1, and TXNRD1 along with increased AMPK phosphorylation were noted in uncontrolled diabetic rats treated with rimonabant. The observed potent inhibitory effects of CB1 receptor blockade on hepatic fat infiltration and cellular death in severely uncontrolled diabetic rats indicate that CB1 receptor is a possible therapeutic target. Increased Nrf2 and AMPK phosphorylation may play a role in the mechanism of rimonabant action.
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