Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis

Shen, Meikun; Shi, Haifei

doi:10.1155/2015/294278

Cited by 183 publications

(156 citation statements)

References 130 publications

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“…[37] Estrogens influence TG accumulation, increase HDL-C levels, and modulate the expression of lipoprotein lipase, which catalyzes the conversion of TG into free fatty acid in the liver. As UL is an estrogen-related tumor, a relationship is believed to exist between dyslipidemia and the risk of UL, and consistent with this hypothesis, in the present study, the prevalences of low HDL-C and of LDL-C levels were significantly higher in UL group.…”

Section: Discussionmentioning

confidence: 99%

Association between uterine leiomyoma and metabolic syndrome in parous premenopausal women

et al. 2016

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Previous studies have reported that uterine leiomyoma (UL) may share pathogenic features with obesity and hypertension, which are components of metabolic syndrome (MetS). We examined the association between UL and MetS in premenopausal parous women.This 1:1 case–control study was conducted on 615 asymptomatic women with UL and 615 women without UL that were matched for age, reproductive history, and hormonal use, who underwent a comprehensive health examination. UL was diagnosed by a gynecologist based on transvaginal ultrasonography findings. Blood pressure (BP), body composition, fasting plasma glucose, lipid profiles, insulin, and HOMA-IR were checked.Median age of the 1230 study subjects was 44 (40–47) years and 7% had MetS. Women with UL had significantly higher waist circumferences and body fat, BP, and low-density lipoprotein cholesterol (LDL-C) than women without UL. Although nonsignificant, the prevalence of MetS was higher in the UL group than in the non-UL group (9.3% vs 5.7%). In addition, the prevalence of UL increased as the number of abnormal metabolic components increased and was higher than in women without UL. Conditional logistic regression analysis, after adjustment for confounding factors, showed that hyperglycemia was significantly associated with an increased risk of UL (odds ratio = 1.45; 95% confidence interval, 1.10–1.89).Prevalence of abnormal metabolic component was higher in premenopausal women with UL than in normal controls, regardless of age or reproductive history. Furthermore, the study suggests that UL may share pathogenic features with the components of MetS and that women with UL be considered eligible for the early screening of metabolic abnormalities.

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Section: Discussionmentioning

confidence: 99%

Association between uterine leiomyoma and metabolic syndrome in parous premenopausal women

et al. 2016

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“…The liver is one of the key organs coordinately controlling energy homeostasis, including lipid metabolism. Hepatic estrogen signaling is critical for maintaining lipid homeostasis in the liver (Han et al, 2014;Shen and Shi, 2015). Nonalcoholic fatty liver disease (NAFLD), primarily manifested by excessive fat accumulation in hepatocytes, has become the most common chronic liver disease worldwide (Demir et al, 2015).…”

Section: Introductionmentioning

confidence: 99%

Nuclear Factor Erythroid 2–Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen

Wei

Zou

Lee

et al. 2016

The Journal of Pharmacology and Experimental Therapeutics

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Transcription factor nuclear factor erythroid 2-related factor 2 (Nrf2) regulates multiple biologic processes, including hepatic lipid metabolism. Estrogen exerts actions affecting energy homeostasis, including a liver fat-lowering effect. Increasing evidence indicates the crosstalk between these two molecules. The aim of this study was to evaluate whether Nrf2 modulates estrogen signaling in hepatic lipid metabolism. Nonalcoholic fatty liver disease (NAFLD) was induced in wild-type and Nrf2-null mice fed a high-fat diet and the liver fat-lowering effect of exogenous estrogen was subsequently assessed. We found that exogenous estrogen eliminated 49% and 90% of hepatic triglycerides in wild-type and Nrf2-null mice with NAFLD, respectively. This observation demonstrates that Nrf2 signaling is antagonistic to estrogen signaling in hepatic fat metabolism; thus, Nrf2 absence results in striking amplification of the liver fat-lowering effect of estrogen. In addition, we found the association of trefoil factor 3 and fatty acid binding protein 5 with the liver fat-lowering effect of estrogen. In summary, we identified Nrf2 as a novel and potent inhibitor of estrogen signaling in hepatic lipid metabolism. Our finding may provide a potential strategy to treat NAFLD by dually targeting Nrf2 and estrogen signaling.

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“…Total cholesterol levels also showed different properties by sex. Sex hormones and their receptors regulate lipid, glucose, and cholesterol homeostasis in the liver (Shen and Shi, 2015); therefore, sex hormones might play some roles in the hepatotoxicity of Synepirin 500.…”

Section: Discussionmentioning

confidence: 99%

A 28-day repeated oral-dose toxicity study of insecticide synergist N-(2-ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2] oct-5-ene-2,3-dicarboximide in rats

Matsumoto¹,

Furukawa

Kobayashi³

et al. 2018

Fundam. Toxicol. Sci.

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-N-(2-Ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2]oct-5-ene-2,3-dicarboximide (Synepirin 500; CAS: 13358-11-7) is used as a synergist, a chemical that makes pesticide ingredients more effective. People can be exposed to Synepirin 500 by using insecticides containing this chemical or from residues in food. The Japanese government chose this chemical as a target substance in its existing chemical testing program. Crl:CD(SD) rats were administered 0, 40, 200, and 1000 mg/kg/day Synepirin 500 by gavage for 28 days, followed by a 14 day recovery period. Diarrhea or soft feces were observed in both sexes at 1000 mg/kg/day. Absolute and/or relative liver weights significantly increased at ≥ 40 mg/kg/day in females and at ≥ 200 mg/kg/day in males. Absolute and/or relative thyroid weights significantly increased in both sexes at 1000 mg/kg/day. These changes were still significant at the end of the recovery period in females. Significantly prolonged prothrombin time and activated partial thromboplastin time were observed in males receiving ≥ 40 mg/kg/day. Histopathological changes in the liver and thyroid were observed in both sexes at 1000 mg/kg/day. On the basis of the effects on the liver, the level of the lowest observed adverse effect from repeated doses of Synepirin 500 was judged to be 40 mg/kg/day for rats.

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Sex Hormones and Their Receptors Regulate Liver Energy Homeostasis

Cited by 183 publications

References 130 publications

Association between uterine leiomyoma and metabolic syndrome in parous premenopausal women

Association between uterine leiomyoma and metabolic syndrome in parous premenopausal women

Nuclear Factor Erythroid 2–Related Factor 2 Deficiency Results in Amplification of the Liver Fat-Lowering Effect of Estrogen

A 28-day repeated oral-dose toxicity study of insecticide synergist N-(2-ethylhexyl)-1-isopropyl-4-methylbicyclo[2.2.2] oct-5-ene-2,3-dicarboximide in rats

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