ArticleThe Journal of endocrinology2021
DHT causes liver steatosis via transcriptional regulation of SCAP in normal weight female mice.
Article in The Journal of endocrinology, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.
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Who cites it
24 citing papers in PubMed, 28 citations in OpenAlex.
- Liver androgen receptor knockout protects female mice from high fat diet-induced insulin resistance.npj metabolic health and disease · 2026Article
- Androgen excess uncouples circulating and hepatic lipid homeostasis in females on a high-calorie diet.Journal of lipid research · 2026Article
- Liver androgen receptor knockout attenuates high-fructose diet-induced glucose dysregulation in female mice.American journal of physiology. Endocrinology and metabolism · 2025Article
- Baicalin mitigates polycystic ovary syndrome‑associated non‑alcoholic fatty liver disease by inhibiting the AR/SREBP1 axis.International journal of molecular medicine · 2025Article
- Article
- Postnatal overfeeding induces gut microbiota disturbances and impairs GPR43/FIAF/LPL pathway in the rat model of PCOS.Journal of physiology and biochemistry · 2025Article
- Biochemical, sex hormonal, and anthropometric predictors of non-alcoholic fatty liver disease in polycystic ovary syndrome.BMC women's health · 2025Article
- Endocannabinoid System and Metabolism: The Influences of Sex.International journal of molecular sciences · 2024Review
- Mechanism of Metabolic Dysfunction-associated Steatotic Liver Disease: Important role of lipid metabolism.Journal of clinical and translational hepatology · 2024Review
- Review
- Regulation and targeting of SREBP-1 in hepatocellular carcinoma.Cancer metastasis reviews · 2024Review
- Androgens exacerbate hepatic triglyceride accumulation in rats with polycystic ovary syndrome by downregulating MTTP expression.Endocrine · 2024Article
- Liver Androgen Receptor Knockout Improved High-fat Diet Induced Glucose Dysregulation in Female Mice But Not Male Mice.Journal of the Endocrine Society · 2024Article
- Association of metabolic-dysfunction associated steatotic liver disease with polycystic ovary syndrome.iScience · 2024Review
- Association of hysterectomy with nonalcoholic fatty liver disease among US women.Lipids in health and disease · 2024Article
- Non-alcoholic fatty liver disease in women - Current knowledge and emerging concepts.JHEP reports : innovation in hepatology · 2023Review
- Controlled attenuation parameters to assess liver steatosis in obese patients with polycystic ovary syndrome.Frontiers in endocrinology · 2023Article
- Key events in cancer: Dysregulation of SREBPs.Frontiers in pharmacology · 2023Review
- The Role of Insulin Resistance in Fueling NAFLD Pathogenesis: From Molecular Mechanisms to Clinical Implications.Journal of clinical medicine · 2022Review
- The Hepatoprotective and Hepatotoxic Roles of Sex and Sex-Related Hormones.Frontiers in immunology · 2022Review
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Authors and funding
9 authors at 5 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hyperandrogenemia (HA) is a hallmark of polycystic ovary syndrome (PCOS) and is an integral element of non-alcoholic fatty liver disease (NALFD) in females. Administering low-dose dihydrotestosterone (DHT) induced a normal weight PCOS-like female mouse model displaying NAFLD. The molecular mechanism of HA-induced NAFLD has not been fully determined. We hypothesized that DHT would regulate hepatic lipid metabolism via increased SREBP1 expression leading to NAFLD. We extracted liver from control and low-dose DHT female mice; and performed histological and biochemical lipid profiles, Western blot, immunoprecipitation, chromatin immunoprecipitation, and real-time quantitative PCR analyses. DHT lowered the 65 kD form of cytosolic SREBP1 in the liver compared to controls. However, DHT did not alter the levels of SREBP2 in the liver. DHT mice displayed increased SCAP protein expression and SCAP-SREBP1 binding compared to controls. DHT mice exhibited increased AR binding to intron-8 of SCAP leading to increased SCAP mRNA compared to controls. FAS mRNA and protein expression was increased in the liver of DHT mice compared to controls. p-ACC levels were unaltered in the liver. Other lipid metabolism pathways were examined in the liver, but no changes were observed. Our findings support evidence that DHT increased de novo lipogenic proteins resulting in increased hepatic lipid content via regulation of SREBP1 in the liver. We show that in the presence of DHT, the SCAP-SREBP1 interaction was elevated leading to increased nuclear SREBP1 resulting in increased de novo lipogenesis. We propose that the mechanism of action may be increased AR binding to an ARE in SCAP intron-8.
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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.