ArticleAmerican journal of physiology. Endocrinology and metabolism2014
Estrogen signaling prevents diet-induced hepatic insulin resistance in male mice with obesity.
Article in American journal of physiology. Endocrinology and metabolism, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 121 citations in OpenAlex.
- Metabolic drivers of MASLD and MASH: from hormonal imbalance to fibrosis.Diabetologia · 2026Review
- Cardiovascular Benefits of Menopause Hormone Treatment is Age-Dependent.bioRxiv : the preprint server for biology · 2026Article
- The Liver-Testis Axis: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 2026Review
- The regulation of intrahepatic fatty acid partitioning within the human liver: the effect of sex.Clinical science (London, England : 1979) · 2026Review
- Visceral adipose tissue and liver fat on 17-beta estradiol-dominant gender-affirming hormone therapy: A US-based cohort.The Journal of clinical endocrinology and metabolism · 2026Observational
- New insights into sexual dimorphism in cardiometabolic health.Hormones (Athens, Greece) · 2026Review
- Cannabis oil modulates liver alterations and endocannabinoid system changes in a female rat model of diet-induced MASLD.Frontiers in nutrition · 2026Article
- Estradiol negatively associates with metabolic dysfunction-associated steatotic liver disease in children.Frontiers in endocrinology · 2026Article
- Article
- Role of obesity and estrogen deficiency in non‑alcoholic fatty liver disease: Insights from a mouse model.Molecular medicine reports · 2025Article
- Adipose Tissue Estrogen Receptor-Alpha Overexpression Ameliorates High-Fat Diet-Induced Adipose Tissue Inflammation.Journal of the Endocrine Society · 2025Article
- Non-linear relationship between the hepatic steatosis index and glycemic progression: evidence from a large-scale retrospective cohort study in a Chinese population.BMC gastroenterology · 2025Article
- Metabolic Messengers: oestradiol.Nature metabolism · 2025Review
- Hepatic Estrogen Receptor Alpha Overexpression Protects Against Hepatic Insulin Resistance and MASLD.Pathophysiology : the official journal of the International Society for Pathophysiology · 2025Article
- Sex-specific associations between the triglyceride-glucose index and new-onset hypertension in a hospital employee cohort: evidence from longitudinal annual health examinations.Frontiers in endocrinology · 2025Article
- Effects and Mechanism ofCombinatorial chemistry & high throughput screening · 2025Article
- Spaceflight induces changes in gene expression profiles linked to insulin and estrogen.Communications biology · 2024Article
- The Effect of Menopausal Status, Insulin Resistance and Body Mass Index on the Prevalence of Non-Alcoholic Fatty Liver Disease.Healthcare (Basel, Switzerland) · 2024Review
- An estrogen receptor α-derived peptide improves glucose homeostasis during obesity.Nature communications · 2024Article
- Estrogen receptor activation remodels TEAD1 gene expression to alleviate hepatic steatosis.Molecular systems biology · 2024Article
17 more citing papers are in PubMed but not listed here.
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Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
The development of insulin resistance in the liver is a key event that drives dyslipidemia and predicts diabetes and cardiovascular risk with obesity. Clinical data show that estrogen signaling in males helps prevent adiposity and insulin resistance, which may be mediated through estrogen receptor-α (ERα). The tissues and pathways that mediate the benefits of estrogen signaling in males with obesity are not well defined. In female mice, ERα signaling in the liver helps to correct pathway-selective insulin resistance with estrogen treatment after ovariectomy. We assessed the importance of liver estrogen signaling in males using liver ERα-knockout (LKO) mice fed a high-fat diet (HFD). We found that the LKO male mice had decreased insulin sensitivity compared with their wild-type floxed (fl/fl) littermates during hyperinsulinemic euglycemic clamps. Insulin failed to suppress endogenous glucose production in LKO mice, indicating liver insulin resistance. Insulin promoted glucose disappearance in LKO and fl/fl mice similarly. In the liver, insulin failed to induce phosphorylation of Akt-Ser(473) and exclude FOXO1 from the nucleus in LKO mice, a pathway important for liver glucose and lipid metabolism. Liver triglycerides and diacylglycerides were also increased in LKO mice, which corresponded with dysregulation of insulin-stimulated ACC phosphorylation and DGAT1/2 protein levels. Our studies demonstrate that estrogen signaling through ERα in the liver helps prevent whole body and hepatic insulin resistance associated with HFD feeding in males. Augmenting hepatic estrogen signaling through ERα may lessen the impact of obesity on diabetes and cardiovascular risk in males.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.