ArticleInternational journal of obesity (2005)2017
Hormone signaling and fatty liver in females: analysis of estrogen receptor α mutant mice.
Article in International journal of obesity (2005), 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 54 papers.
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Who cites it
54 citing papers in PubMed, 95 citations in OpenAlex.
- The Liver-Testis Axis: Molecular Mechanisms and Clinical Implications.International journal of molecular sciences · 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
- Single-cell transcriptomics reveals the impact of sex and age in the healthy human liver.JHEP reports : innovation in hepatology · 2026Article
- Sex and gender differences in metabolic dysfunction-associated liver disease.Indian journal of gastroenterology : official journal of the Indian Society of Gastroenterology · 2026Review
- Sex-Specific Metabolic Footprint of Ketogenic Diet in C57BL/6J Mice.Biomedicines · 2026Article
- Sex‑specific cardiovascular risk in estrogen‑treated androgen‑deprived males: metabolic characterization of glucose, adipose, and lipid pathways.Cardiovascular diabetology · 2026Article
- High estradiol/testosterone ratio increased the risk of metabolic dysfunction-associated steatotic liver disease in men with type 2 diabetes mellitus.Journal of diabetes investigation · 2026Observational
- Interplay between endocrine disorders and liver dysfunction: Mechanisms of damage and therapeutic approaches.World journal of gastroenterology · 2025Review
- Ultraviolet exposure of mice fed a high fat diet reduces weight gain and markers of liver disease progression.International journal of obesity (2005) · 2025Article
- Article
- Relationship between serum uric acid levels and metabolism associated fatty liver disease in postmenopausal women based on NHANES 2017-2020.Scientific reports · 2025Observational
- Mechanism and therapeutic potential of liver injury induced by cholesterol-associated proteins.Frontiers in pharmacology · 2025Review
- Low dose exposure to dioxins alters hepatic energy metabolism and steatotic liver disease development in a sex-specific manner.Environment international · 2024Article
- Pathogenesis and research progress of nonalcoholic fatty liver disease/nonalcoholic steatohepatitis.World journal of hepatology · 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
- Perinatal maternal undernutrition in baboons modulates hepatic mitochondrial function but not metabolites in aging offspring.bioRxiv : the preprint server for biology · 2024Article
- Targeting nuclear receptors for NASH/MASH: From bench to bedside.Liver research (Beijing, China) · 2024Article
- Diabetes mellitus in breast cancer survivors: metabolic effects of endocrine therapy.Nature reviews. Endocrinology · 2024Review
- 17β-Estradiol (EAntioxidants (Basel, Switzerland) · 2023Article
- Machine Learning Enables Single-Score Assessment of MASLD Presence and Severity.medRxiv : the preprint server for health sciences · 2023Article
Corrections and comments
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundTreatment with estrogen in early menopausal women protects against development of hepatic steatosis and nonalcoholic fatty liver disease but estrogen has undesirable side effects, which negate its beneficial effects in premenopausal and postmenopausal women. Targeted therapies require better understanding of the target sites and mechanisms by which estrogen signaling exerts its protective effects in women. Estrogen receptor α (ERα) is thought to be the primary mediator for estrogen signaling to protect against hepatic steatosis. ERα has several mechanisms for signal transduction: (1) inducing gene transcription by direct binding to specific DNA sequences, (2) inducing tethered transcription with other DNA-binding factors, and (3) stimulating nongenomic action through membrane-associated ERα. However, it is still unclear which mechanisms mediate ERα-dependent protection against hepatic steatosis.
methodsTo understand the mechanisms of estrogen signaling for protection against hepatic steatosis in females, we analyzed the global ERα knockout mouse (αERKO), ERα DNA-binding domain mutant mouse (KIKO) and liver-specific ERα knockout mouse (LERKO) fed high-fat diets (HFD). The KIKO mouse disrupts the direct DNA-binding transcription activity but retains tethered transcription regulation and nongenomic action. Hepatic steatosis was evaluated by scoring the macrovesicular and microvesicular steatosis as well as serum alanine aminotransferase (ALT) levels. We analyzed serum testosterone to assess its correlation with hepatic steatosis.
resultsLiver fat accumulation was far greater in HFD-fed αERKO and KIKO females than in HFD-fed wild-type (WT) controls. Conversely, HFD-fed LERKO females did not accumulate excess liver fat. HFD-fed αERKO and KIKO females showed higher microvesicular steatosis and ALT levels than WT controls that correlated with increased serum testosterone levels.
conclusionsERα-mediated direct transcription in non-hepatic tissues is essential for estrogen-mediated protection against hepatic steatosis in HFD-fed females. The balance between non-hepatic estrogen signaling and hepatic or non-hepatic testosterone action may control hepatic steatosis.
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