Research Article Details
| Article ID: | A17878 |
| PMID: | 27506737 |
| Source: | Metabolism |
| Title: | Adiponectin as a target for the treatment of nonalcoholic steatohepatitis with thiazolidinediones: A systematic review. |
| Abstract: | Thiazolidinediones (TZDs; pioglitazone and rosiglitazone) have provided promising results in clinical trials for nonalcoholic steatohepatitis (NASH). The main purpose of this systematic review was to summarize evidence on circulating adiponectin levels in relation to histological changes following TZD treatment in patients with histologically confirmed NASH. We performed a systematic search in PubMed, Scopus and Cochrane Library. We included four studies, published between 2006 and 2012, providing data for 187 histologically confirmed NASH adult patients (105 on TZD and 82 controls) treated for 6-12months. Significant increase in adiponectin (80-178%) after TZD treatment was observed in all included studies. Improvement in steatosis following treatment was observed in all studies. A trend towards improvement in lobular inflammation was observed in all studies after pioglitazone, but not after rosiglitazone. Trends toward improvement in ballooning and fibrosis were observed in the two studies after pioglitazone using either the highest doses or the longest duration of therapy. Overall disease activity score was improved in all studies after pioglitazone, but not after rosiglitazone. Insulin resistance and liver function tests were also improved after treatment. Despite weight gain, circulating leptin was not increased after treatment. In conclusion, parallel increases in circulating adiponectin levels and histological improvement were observed in this systematic review. These results warrant further consideration of TZDs, but even more importantly point to a key role for novel potential treatments for NASH patients such as the newer selective peroxisome proliferator activated receptor-γ modulators, which increase adiponectin without significant weight gain. |
| DOI: | 10.1016/j.metabol.2016.05.013 |
| 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D275 | Pioglitazone | Chemical drug | DB01132 | PPARG agonist | Improve insulin resistance | Advanced in clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D311 | Rosiglitazone | Chemical drug | DB00412 | PPARG agonist; PPARA; PPARD | Improve insulin resistance | Failed in clinical trials | Details |