Research Article Details
| Article ID: | A52219 |
| PMID: | 29980484 |
| Source: | Mol Metab |
| Title: | FGF21 regulates insulin sensitivity following long-term chronic stress. |
| Abstract: | OBJECTIVE: Post-traumatic stress disorder (PTSD) increases type 2 diabetes risk, yet the underlying mechanisms are unclear. We investigated how early-life exposure to chronic stress affects long-term insulin sensitivity. METHODS: C57Bl/6J mice were exposed to chronic variable stress for 15 days (Cvs) and then recovered for three months without stress (Cvs3m). RESULTS: Cvs mice showed markedly increased plasma corticosterone and hepatic insulin resistance. Cvs3m mice exhibited improved whole-body insulin sensitivity along with enhanced adipose glucose uptake and skeletal muscle mitochondrial function and fatty acid oxidation. Plasma FGF21 levels were substantially increased and associated with expression of genes involved in fatty acid oxidation and formation of brown-like adipocytes. In humans, serum FGF21 levels were associated with stress coping long time after the exposure. CONCLUSIONS: Early-life exposure to chronic stress leads to long term improvements in insulin sensitivity, oxidative metabolism and adipose tissue remodeling. FGF21 contributes to a physiological memory mechanism to maintain metabolic homeostasis. |
| DOI: | 10.1016/j.molmet.2018.06.012 |
| 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 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |