Research Article Details
| Article ID: | A50095 |
| PMID: | 35528989 |
| Source: | J Clin Transl Hepatol |
| Title: | Glutaminolysis-ammonia-urea Cycle Axis, Non-alcoholic Fatty Liver Disease Progression and Development of Novel Therapies. |
| Abstract: | The prevalence of non-alcoholic fatty liver disease (NAFLD) is increasing worldwide, reflecting the current epidemics of obesity, insulin resistance, type 2 diabetes mellitus, and metabolic syndrome. NAFLD is characterized by the accumulation of fat in the liver, and is known to be a cause of cirrhosis. Although many pathways have been proposed, the cause of NAFLD-linked fibrosis progression is still unclear, which posed challenges for the development of new therapies to prevent NASH-related cirrhosis and hepatocellular carcinoma. Cirrhosis is associated with activation of hepatic stellate cells (HSC) and accumulation of excess extracellular matrix proteins, and inhibiting the activation of HSCs would be expected to slow the progression of NAFLD-cirrhosis. Multiple molecular signals and pathways such as oxidative stress and glutaminolysis have been reported to promote HSC activation. Both mechanisms are plausible antifibrotic targets in NASH, as the activation of HSCs the proliferation of myofibroblasts depend on those processes. This review summarizes the role of the glutaminolysis-ammonia-urea cycle axis in the context of NAFLD progression, and shows how the axis could be a novel therapeutic target. |
| DOI: | 10.14218/JCTH.2021.00247 |
| 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 |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | 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 | |
|---|---|---|---|---|---|---|---|
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | 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 |