ArticleAmerican journal of physiology. Regulatory, integrative and comparative physiology2022
Targeting mineralocorticoid receptors in diet-induced hepatic steatosis and insulin resistance.
Article in American journal of physiology. Regulatory, integrative and comparative physiology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 15 citations in OpenAlex.
- Unveiling the role of aldosterone in metabolic dysfunction-associated steatotic liver disease.Reviews in endocrine & metabolic disorders · 2026Review
- Targeting the aldosterone-mineralocorticoid receptor pathway in cardiovascular-kidney-metabolic syndrome.Nature reviews. Nephrology · 2026Review
- The impact of mineralocorticoid receptor antagonists on fat mass and fat metabolism.Journal of endocrinological investigation · 2026Review
- HFpEF and MASLD: converging mechanisms and clinical implications.Nature reviews. Cardiology · 2026Review
- GENETIC AND PHARMACOLOGIC ACTIVATION OF BECLIN1 PREVENTS ALDOSTERONE-INDUCED CARDIOVASCULAR DAMAGE.bioRxiv : the preprint server for biology · 2026Article
- SGK1 inhibition exerts atheroprotective effects in vascular endothelial cells.Biochemistry and biophysics reports · 2026Article
- The link between dietary inflammation and hyperuricemia: what is the mediating role of insulin resistance and abdominal obesity?Nutrition & metabolism · 2026Article
- A novel mineralocorticoid receptor blocker, CS-3150, improves insulin resistance and reduces inflammation in db/db mice.The Korean journal of physiology & pharmacology : official journal of the Korean Physiological Society and the Korean Society of Pharmacology · 2026Article
- Gradual DNA methylation changes reveal transcription factors implicated in metabolic dysfunction-associated steatotic liver disease progression and epigenetic age acceleration.Clinical epigenetics · 2025Article
- Linking Cardiovascular Disease and Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): The Role of Cardiometabolic Drugs in MASLD Treatment.Biomolecules · 2025Review
- Enhanced ECCD36 signaling promotes skeletal muscle insulin resistance in female mice.American journal of physiology. Endocrinology and metabolism · 2024Article
- The mineralocorticoid receptor in diabetic kidney disease.American journal of physiology. Renal physiology · 2024Review
- Diabetic Vasculopathy: Molecular Mechanisms and Clinical Insights.International journal of molecular sciences · 2024Review
- Vascular endothelial mineralocorticoid receptors and epithelial sodium channels in metabolic syndrome and related cardiovascular disease.Journal of molecular endocrinology · 2023Review
- Mechanisms Linking Metabolic-Associated Fatty Liver Disease (MAFLD) to Cardiovascular Disease.Current hypertension reports · 2023Review
- Endothelial MRs Mediate Western Diet-Induced Lipid Disorders and Skeletal Muscle Insulin Resistance in Females.Endocrinology · 2023Article
- Cardiovascular Disease in Obstructive Sleep Apnea: Putative Contributions of Mineralocorticoid Receptors.International journal of molecular sciences · 2023Review
- Mineralocorticoid Receptors Mediate Diet-Induced Lipid Infiltration of Skeletal Muscle and Insulin Resistance.Endocrinology · 2022Article
- Mineralocorticoid Receptor Activation in Vascular Insulin Resistance and Dysfunction.International journal of molecular sciences · 2022Review
- Recent Advances in the Treatment of Insulin Resistance Targeting Molecular and Metabolic Pathways: Fighting a Losing Battle?Medicina (Kaunas, Lithuania) · 2022Review
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Mineralocorticoid receptor (MR) activation plays an important role in hepatic insulin resistance. However, the precise mechanisms by which MR activation promotes hepatic insulin resistance remains unclear. Therefore, we sought to investigate the roles and mechanisms by which MR activation promotes Western diet (WD)-induced hepatic steatosis and insulin resistance. Six-week-old C57BL6J mice were fed either mouse chow or a WD, high in saturated fat and refined carbohydrates, with or without the MR antagonist spironolactone (1 mg/kg/day) for 16 wk. WD feeding resulted in systemic insulin resistance at 8 and 16 wk. WD also induced impaired hepatic insulin metabolic signaling via phosphoinositide 3-kinases/protein kinase B pathways, which was associated with increased hepatic CD36, fatty acid transport proteins, fatty acid-binding protein-1, and hepatic steatosis. Meanwhile, consumption of a WD-induced hepatic mitochondria dysfunction, oxidative stress, and inflammatory responses. These abnormalities occurring in response to WD feeding were blunted with spironolactone treatment. Moreover, spironolactone promoted white adipose tissue browning and hepatic glucose transporter type 4 expression. These data suggest that enhanced hepatic MR signaling mediates diet-induced hepatic steatosis and dysregulation of adipose tissue browning, and subsequent hepatic mitochondria dysfunction, oxidative stress, inflammation, as well as hepatic insulin resistance.
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