ArticlePloS one2017
Gender difference in NASH susceptibility: Roles of hepatocyte Ikkβ and Sult1e1.
Article in PloS one, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed.
- Perioperative comparison between robotic-assisted and freehand total knee arthroplasty : A quasi-randomized controlled trial.Orthopadie (Heidelberg, Germany) · 2026Trial
- Hepatic SIRT6 Deficiency Accelerates Female-Specific Aging Through SULT1E1-Mediated Estrogen Depletion.International journal of molecular sciences · 2026Article
- Metabolic Syndrome Nonalcoholic Steatohepatitis Male Mouse With Adeno-Associated Viral Renin as a Novel Model for Heart Failure With Preserved Ejection Fraction.Journal of the American Heart Association · 2024Article
- Mitochondrial topoisomerase I (Top1MT) prevents the onset of metabolic dysfunction-associated steatohepatitis (MASH) in mice.bioRxiv : the preprint server for biology · 2024Article
- Fatty Liver Index (FLI) is the best score to predict MASLD with 50% lower cut-off value in women than in men.Biology of sex differences · 2024Observational
- New insights into the suppression of inflammation and lipid accumulation byGenes & diseases · 2023Review
- Integrative proteomic and lipidomic analysis of Kaili Sour Soup-mediated attenuation of high-fat diet-induced nonalcoholic fatty liver disease in a rat model.Nutrition & metabolism · 2021Article
- RNA-Seq Reveals Different Gene Expression in Liver-Specific Prohibitin 1 Knock-Out Mice.Frontiers in physiology · 2021Article
- Comparison of Clinical Characteristics Between Obese and Non-Obese Patients with Nonalcoholic Fatty Liver Disease (NAFLD).Diabetes, metabolic syndrome and obesity : targets and therapy · 2021Article
- Nonalcoholic fatty liver disease and alcohol-related liver disease: From clinical aspects to pathophysiological insights.Clinical and molecular hepatology · 2020Article
- RORα phosphorylation by casein kinase 1α as glucose signal to regulate estrogen sulfation in human liver cells.The Biochemical journal · 2020Article
- The Role of Sulfotransferases in Liver Diseases.Drug metabolism and disposition: the biological fate of chemicals · 2020Review
- Insulin Fused to Apolipoprotein A-I Reduces Body Weight and Steatosis in DB/DB Mice.Frontiers in pharmacology · 2020Article
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9 authors.
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Abstract
Myeloid cell and hepatocyte IKKβ may mediate the genesis of obesity and insulin resistance in mice fed high fat diet. However, their gender-specific roles in the pathogenesis of non-alcoholic steatohepatitis (NASH) are not known. Here we demonstrate myeloid IKKβ deficiency prevents Western diet-induced obesity and visceral adiposity in females but not in males, and attenuates hyperglycemia, global IR, and NASH in both genders. In contrast, all metabolic sequela including NASH are aggravated by hepatocyte IKKβ deficiency (IkbkbΔhep) in male but not female mice. Gene profiling identifies sulfotransferase family 1E (Sult1e1), which encodes a sulfotransferase E1 responsible for inactivation of estrogen, as a gene upregulated in NASH in both genders and most conspicuously in male IkbkbΔhep mice having worst NASH and lowest plasma estradiol levels. LXRα is enriched to LXRE on Sult1e1 promoter in male WT and IkbkbΔhep mice with NASH, and a Sult1e1 promoter activity is increased by LXRα and its ligand and augmented by expression of a S32A mutant of IκBα. These results demonstrate striking gender differences in regulation by IKKβ of high cholesterol saturated fat diet-induced metabolic changes including NASH and suggest hepatocyte IKKβ is protective in male due at least in part to its ability to repress LXR-induced Sult1e1. Our findings also raise a caution for systemic IKK inhibition for the treatment of NASH as it may exacerbate the disease in male patients.
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