Research Article Details
| Article ID: | A33285 |
| PMID: | 26301053 |
| Source: | World J Hepatol |
| Title: | Recent advances in mouse models of obesity- and nonalcoholic steatohepatitis-associated hepatocarcinogenesis. |
| Abstract: | Hepatocellular carcinoma (HCC) is the fifth most common cancer, and obesity has been established as a risk factor for HCC development. Nonalcoholic steatohepatitis (NASH) is apparently the key link between obesity and hepatocarcinogenesis, and obesity also accelerates HCC development synergistically with other risk factors, such as hepatitis virus infection and alcohol consumption. As an explanation for the pathogenesis of NASH, the so-called "two-hit" theory has been widely accepted, but recently, a better model, the so-called "multiple-hits hypothesis" was proposed, which states that many disease-promoting factors may occur in parallel, rather than consecutively. However, the overall mechanism remains largely unknown. Various cell-cell and organ-organ interactions are involved in the pathogenesis of NASH, and thus appropriate in vivo disease models are essential for a deeper understanding. However, replicating the full spectrum of human NASH has been difficult, as NASH involves obesity, insulin resistance, steatohepatitis, fibrosis, and ultimately HCC, and the lack of an appropriate mouse model has been a considerable barrier to determining the missing links among obesity, NASH, and HCC. In recent years, several innovative mouse models presenting obesity- and NASH-associated HCC have been established by modified diets, chemotoxic agents, genetic manipulation, or a combination of these factors, shedding some light on this complex network and providing new therapeutic strategies. Thus, in this paper, I review the mouse models of obesity- and NASH-associated HCC, especially focusing on recent advances and their clinical relevance. |
| DOI: | 10.4254/wjh.v7.i17.2110 |
| 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 |
| 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 |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |