Research Article Details
| Article ID: | A19740 |
| PMID: | 26380042 |
| Source: | World J Hepatol |
| Title: | Targeting Kupffer cells in non-alcoholic fatty liver disease/non-alcoholic steatohepatitis: Why and how? |
| Abstract: | Mechanisms for non-alcoholic steatohepatitis (NASH) development are under investigation in an era of increased prevalence of obesity and metabolic syndrome. Previous findings have pointed to the role of adipose tissue, adipose tissue macrophages and their secretory products in the development of a chronic inflammatory status inducing insulin resistance and a higher risk of liver steatosis called non-alcoholic fatty liver disease. The activation of resident macrophages [Kupffer cells (KC)] and the recruitment of blood derived monocytes/macrophages into the diseased liver have now been identified as key elements for disease initiation and progression. Those cells could be activated through gut flora modifications and an altered gut barrier function but also through the internalization of toxic lipid compounds in adjacent hepatocytes or in KC themselves. Due to the role of activated KC in insulin resistance, fibrosis development and inflammation amplification, they became a target in clinical trials. A shift towards an anti-inflammatory KC phenotype through peroxisome proliferator activator-receptorδ agonists, an inhibition of macrophage recruitment through anti-C-C chemokine receptor 2 action and a specific blocking of internalization of toxic lipoxidation or glycation compounds into KC by galectin-3 receptor inhibitors are now under investigation in human NASH. |
| DOI: | 10.4254/wjh.v7.i19.2184 |
| 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 |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | 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 |