Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease
Abstract
1. Introduction
2. Steroid Hormones and Cognate Receptors
2.1. Steroid Hormones
2.1.1. Estrogens
2.1.2. Androgens
2.1.3. Progestogens
2.1.4. Glucocorticoids
2.1.5. Mineralocorticoids
2.1.6. Vitamin D
2.2. Steroid Hormone Receptors
3. Role of Steroid Hormones in Hepatic Steatosis and Metabolism
Steroid Hormones | Model(s) Used | Major Phenotypes Examined |
---|---|---|
Estrogen | - Female ERα-deficient mice fed HFD for 10 weeks [71] - Male hepatic ERα-deficient mice fed HFD for 12 weeks [72] - OVX mice treated with E2 and fed HFD for 6 weeks [74] | - Liver weight, hepatic steatosis, and ALT level ↑ - Hepatic steatosis and insulin resistance ↑ - Hepatic steatosis and insulin- mediated suppression of VLDL secretion ↓ |
Androgen | - Male hepatic AR-deficient mice fed HFD for 8 weeks [76] | - Body weight, hepatic steatosis, and insulin resistance ↑ |
Glucocorticoid | - db/db mice treated with GC shRNA for 14 days [77] - SD rats treated with exogenous corticosterone and fed HFD for 16 days [78] | - Hepatic steatosis and genes critical for lipid storage and transport ↓ - Hepatic steatosis, uptake of FA into liver, and ALT level ↑ |
Mineralocorticoid | - Myeloid MR-deficient ob/ob mice [79] - Aldosterone synthase-deficient mice fed HFD for 12 weeks [80] | - Hepatic steatosis, lipogenesis, and insulin resistance ↓ - HFD-feeding-induced hepatic steatosis ↓ |
Vitamin D | - C57BL6 mice fed a high-fat/ high-sucrose diet followed by treatment with vitamin D for 15 weeks [81] - SD rats fed HFD followed by treatment with vitamin D for 16 weeks [82] | - Hepatic steatosis and hepatic de novo lipogenesis ↓ - Liver weight, hepatic steatosis, and ALT level ↓ |
4. Role of Steroid Hormones in Hepatic Inflammation and Fibrosis
Steroid Hormones | Model (s) Used | Major Phenotypes Examined |
---|---|---|
Estrogen | - OVX mice fed HFD and high-fructose water for 12 weeks [111] - OVX mice fed a high-fat and high-cholic-acid diet for 6 weeks [109] - Old female zebrafish fed a high-calorie diet for 24 weeks [112] - Orchidectomized C57/BL6 mice treated with estradiol benzoate-fed MCD for 4 weeks [110] - Male C57BL6 mice treated with β-LGND2 and fed HFD for 10 weeks [115] | - Hepatic inflammation and fibrosis, ALT level and ballooning degeneration ↑ - Liver fibrosis, inflammation, and hepatocyte ballooning degeneration ↑ - Liver fibrosis, IL-6, and TNF-β ↑ - Hepatic inflammation, MyD88, and IL-6 ↓ - Hepatic steatosis and insulin resistance ↓ |
Androgen | - Orchidectomized male SD rats treated with dihydrotestosterone and fed HFD for 75 days [117] | - Portal inflammation, TNF-α, and IL-6 ↓ |
Progesterone | - Hepatic fibrosis model of New Zealand male rabbits treated with progesterone for 180 days [119] | - Liver fibrosis, fat metamorphosis, and inflammatory infiltrate ↓ |
Glucocorticoid | - Immune cell-specific GR-knockout mice treated with CCl4 and dexamethasone for 6 weeks [120] - HSC-specific GR-knockout mice treated with CCl4 and dexamethasone for 6 weeks [120] | - Inflammation and monocyte recruitment ↓ - Hepatic fibrosis and fibrotic gene expression ↓ |
Mineralocorticoid | - C57BL6 mice fed HFFD mixed with eplerenone for 12 weeks [121] - Male C57BL6 mice fed a CDAA diet for 22 weeks with eplerenone [122] - Male SD rats treated with aldosterone for 4 weeks [123] | - Lipid accumulation, lobular inflammation, and collagen deposition ↓ - Hepatic fibrosis, steatosis, and inflammation ↓ - Hepatic fibrosis, oxidative stress, and DNA double-strand breaks ↑ |
Vitamin D | - Vitamin D-deficient SD rats fed WD for 10 weeks [124] - CDAA diet-induced rat NASH model with phototherapy for 6 or 12 weeks [125] | - Foci of lobular inflammation and ballooning degeneration ↑ - Collagen fibrosis, insulin and leptin resistance, inflammation, and HSC activation ↓ |
5. Conclusions and Perspective
Funding
Conflicts of Interest
References
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Yang, M.; Ma, F.; Guan, M. Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Metabolites 2021, 11, 320. https://doi.org/10.3390/metabo11050320
Yang M, Ma F, Guan M. Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Metabolites. 2021; 11(5):320. https://doi.org/10.3390/metabo11050320
Chicago/Turabian StyleYang, Meng, Feng Ma, and Min Guan. 2021. "Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease" Metabolites 11, no. 5: 320. https://doi.org/10.3390/metabo11050320
APA StyleYang, M., Ma, F., & Guan, M. (2021). Role of Steroid Hormones in the Pathogenesis of Nonalcoholic Fatty Liver Disease. Metabolites, 11(5), 320. https://doi.org/10.3390/metabo11050320