Research Article Details
| Article ID: | A28030 |
| PMID: | 16680031 |
| Source: | Curr Opin Lipidol |
| Title: | New insights in the pathogenesis of non-alcoholic fatty liver disease. |
| Abstract: | PURPOSE OF REVIEW: The hallmark of non-alcoholic fatty liver disease is hepatic steatosis. This is mostly a benign condition, but for largely unknown reasons it progresses to liver fibrosis, cirrhosis, and ultimately hepatocellular carcinoma in about 10% of patients. In this review we discuss recent progress in the understanding of the etiology of non-alcoholic fatty liver disease. RECENT FINDINGS: In the last few years many connections between carbohydrate and triglyceride homeostasis, as well as inflammation, have surfaced. These seemingly unrelated metabolic pathways are linked by the action of diverse nuclear receptors. Many intermediates in lipid metabolism were shown to be activating ligands of these receptors, explaining the dysregulation of intermediary metabolism and induction of insulin resistance by a lipid overload. In addition to invoking a derangement in nuclear receptor regulation, excessive hepatic lipid influx may have direct metabolic consequences, particularly on mitochondrial function. SUMMARY: Non-alcoholic fatty liver disease is a multifactorial disease. Many aspects of the disease and the links to inflammation can be understood when the multiple functions of the regulating nuclear receptors are taken into account. Many of these nuclear receptors seem attractive targets to develop therapy for non-alcoholic fatty liver disease and the closely related metabolic syndrome. |
| DOI: | 10.1097/01.mol.0000226118.43178.98 |
| 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 |
| 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 |
| 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 |