Research Article Details
| Article ID: | A09549 |
| PMID: | 31697646 |
| Source: | Aging (Albany NY) |
| Title: | Catalpol induces autophagy and attenuates liver steatosis in ob/ob and high-fat diet-induced obese mice. |
| Abstract: | Impaired autophagy has been implicated in the pathogenesis of nonalcoholic fatty liver disease. Catalpol (CAT), a bioactive compound from Rehmannia (Di Huang) glutinosa, is known to ameliorate insulin resistance and the histological NAFLD spectrum in obese mice. Here, we investigated the effects of CAT on hepatic steatosis and autophagy in ob/ob and high-fat diet-induced obese mice, as well as in hepatocytes. In ob/ob mice, CAT reduced liver weight, liver triglyceride and cholesterol content, and hepatic lipogenic enzyme levels and increased fatty acid oxidase levels. In addition, CAT administration increased LC3-II levels and decreased SQSTM1/P62 levels in ob/ob mice. Similar effects on hepatic steatosis and autophagy were observed in high-fat diet-induced mice after administration of CAT. Additionally, we found that CAT stimulated AMPK and increased nuclear translocation of transcription factor EB (TFEB) in obese mice and hepatocytes. Inhibition of AMPK completely blocked the effects of CAT on TFEB nuclear localization, hepatic autophagy, and liver steatosis. These findings revealed that diminished AMPK/TFEB-dependent autophagy is involved in the pathogenesis of liver steatosis in obesity, and that CAT might be a novel therapeutic candidate for treatment of this condition. |
| DOI: | 10.18632/aging.102396 |
| 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D545 | Pig placenta extract | Biological extract | -- | -- | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |