Research Article Details
| Article ID: | A46149 |
| PMID: | 20717042 |
| Source: | J Clin Gastroenterol |
| Title: | The potential adverse role of leptin resistance in nonalcoholic fatty liver disease: a hypothesis based on critical review of the literature. |
| Abstract: | BACKGROUND: Leptin is an adipocyte-derived hormone that plays a crucial role in energy homeostasis and lipid metabolism. Most of the biological effects of leptin are exerted through activation of the Janus kinase-2/signal transducer and activator of transcription-3 pathway. Signal transducer and activator of transcription-3 activation ultimately leads to an increased transcription and expression of suppressors of cytokine signaling-3, which acts as a feedback inhibitor by attenuating leptin signaling. Apart from inhibiting leptin signaling, suppressor of cytokine signaling-3 inhibits insulin signaling. Leptin increases with increasing fatty mass as a compensatory mechanism to preserve insulin sensitivity, but persistent hyperleptinemia is implicated in liver fibrinogenesis and carcinogenesis. HYPOTHESIS: Considering this dual role of leptin in the liver pathophysiology, we hypothesized that leptin resistance may vary according to the different types of liver cells and nonalcoholic fatty liver disease progression. CLINICAL CONSEQUENCES: It is speculated that recombinant leptin, proposed to be used in common forms of obesity or nonalcoholic fatty liver disease, might have serious unfavorable therapeutical drawbacks, through promotion of insulin resistance, fibrosis, and hepatocellular carcinoma. |
| DOI: | 10.1097/MCG.0b013e3181ec5c66 |
| 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 |
| 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 |