Research Article Details
| Article ID: | A04157 |
| PMID: | 33736456 |
| Source: | Antioxid Redox Signal |
| Title: | Sex Differences in Nonalcoholic Fatty Liver Disease: Estrogen Influence on the Liver-Adipose Tissue Crosstalk. |
| Abstract: | Significance: Nonalcoholic fatty liver disease (NAFLD) is a hepatic and systemic disorder with a complex multifactorial pathogenesis. Owing to the rising incidence of obesity and diabetes mellitus, the prevalence of NAFLD and its impact on global health care are expected to increase in the future. Differences in NAFLD exist between males and females, and among females depending on their reproductive status. Clinical and preclinical data show that females in the fertile age are more protected against NAFLD, and studies in postmenopausal women and ovariectomized animal models support a protective role for estrogens. Recent Advances: An efficient crosstalk between the liver and adipose tissue is necessary to regulate lipid and glucose metabolism, protecting the liver from steatosis and insulin resistance contributing to NALFD. New advances in the knowledge of sexual dimorphism in liver and adipose tissue are providing interesting clues about the sex differences in NAFLD pathogenesis that could inspire new therapeutic strategies. Critical Issues: Sex hormones influence key master regulators of lipid metabolism and oxidative stress in liver and adipose tissue. All these sex-biased metabolic adjustments shape the crosstalk between liver and adipose tissue, contributing to the higher protection of females to NAFLD. Future Directions: The development of novel drugs based on the protective action of estrogens, but without its feminizing or undesired side effects, might provide new therapeutic strategies for the management of NAFLD. Antioxid. Redox Signal. 35, 753-774. |
| DOI: | 10.1089/ars.2021.0044 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S02 | Enhance lipid metabolism | triglyceride-lowering; lipid tolerance; lipid metabolism | 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) inhibitor; Decreases intestinal cholesterol absorption; FXR agonist; ACC inhibitor; FAS inhibitor; DGAT2 inhibitor; SCD-1 inhibitor | Atorvastatin; Ezetimibe; Obeticholic Acid; GS-9674; GS-0976; TVB-2640; IONIS-DGAT2rx; Aramchol; | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |