Research Article Details
| Article ID: | A24009 |
| PMID: | 23304464 |
| Source: | J Obes |
| Title: | The relationship between nonalcoholic fatty liver disease and colorectal cancer: the future challenges and outcomes of the metabolic syndrome. |
| Abstract: | Nonalcoholic fatty liver disease (NAFLD) is closely related to insulin resistance, metabolic syndrome, obesity, type 2 diabetes, and dyslipidaemia. Obesity and metabolic syndrome are associated with an increased cancer risk, and recent evidence demonstrated an association between NAFLD and colorectal cancer (CRC). The mechanism of how NAFLD can be associated with increased risk of CRC is not fully understood; however, NAFLD represents a condition of profound insulin resistance and a proinflammatory state. Insulin and insulin-like growth factors may promote the development of CRC through their proliferative and antiapoptotic effects. Patients with NAFLD have reduced expression of adiponectin, an adipokine with anti-inflammatory effects. Importantly, hypoadiponectinemia is associated with an increased risk of CRC. Decreased levels of adiponectin lead to increased insulin levels due to marked insulin resistance and in turn increased insulin growth factor-1 (IGF-1). Insulin binds to IGF-1 receptors and plays an important role in cell proliferation, apoptosis, and increased production of vascular endothelial growth factor, an angiogenic factor that supports cancer growth. Further studies are needed to establish (i) the pathophysiology of NAFLD with colorectal cancer, (ii) the benefit of early screening of CRC in NAFLD patients, and (iii) the impact of treatment of NAFLD in the modulation of the risk of colorectal cancer. |
| DOI: | 10.1155/2012/637538 |
| 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 |
| S13 | Anti-apoptosis | hepatocyte apoptosis; hepatic autophagy; apoptosis | Pan-caspase inhibitor | Emricasan | 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 |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I13 | 3146 | Lipid metabolism disorder | An inherited metabolic disorder that involves the creation and degradation of lipids. http://en.wikipedia.org/wiki/Lipid_metabolism | disease of metabolism/ inherited metabolic disorder | Details |
| 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 |