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