Research Article Details
| Article ID: | A27829 |
| PMID: | 17331160 |
| Source: | Alcohol Clin Exp Res |
| Title: | Hypoadiponectinemia plays a crucial role in the development of nonalcoholic fatty liver disease in patients with type 2 diabetes mellitus independent of visceral adipose tissue. |
| Abstract: | BACKGROUND: Nonalcoholic fatty liver disease (NAFLD) is the most common cause of chronic liver injury. The spectrum of NAFLD is broad, extending from simple steatosis through nonalcoholic steatohepatitis (NASH). Insulin resistance has been found to increase the risk of NASH, and obesity, and decreased levels of adiponectin are important factors in determining the severity of insulin resistance. Recent evidence has indicated that hypoadiponectinemia is involved in hepatic steatosis and NASH. METHODS: To investigate whether hypoadiponectinemia causes hepatic steatosis in type 2 diabetes mellitus (DM) patients independently of visceral adipose tissue, we measured the plasma adiponectin concentration, hepatic fat content based on the liver-to-spleen ratio (L/S ratio) according to computed tomography (CT) attenuation values, and the amount of visceral adipose tissue and subcutaneous adipose tissue by CT in 248 type 2 DM patients. We also investigated the relationship between the serum level of adiponectin and hepatic fibrosis. RESULTS: Significant correlations were observed between the L/S ratios and aspartate aminotransferase, alanine aminotransferase, visceral adipose tissue, subcutaneous adipose tissue, and serum adiponectin values (r=0.300, p=0.0007), and there was a highly significant inverse correlation between the visceral adipose tissue values and the serum adiponectin levels (r=-0.327, p<0.0002). The subcutaneous adipose tissue values, however, were not correlated with the serum adiponectin levels. Multiple regression analysis was used to quantify the impact of measured variables on the L/S ratio. After adjustment for age, gender, and visceral adipose tissue, the serum adiponectin levels were still significantly correlated with the L/S ratios (p=0.0064). And there was a stepwise decrease in the serum adiponectin in parallel to the severity of hepatic fibrosis. CONCLUSIONS: Hypoadiponectinemia is concluded to be involved in the etiology of hepatic steatosis independently of visceral adipose tissue content, and is considered to be an important factor in the progression of fibrosis; further studies will be necessary to elucidate the exact physiological role of adiponectin and its contribution to the progression of NASH. |
| DOI: | 10.1111/j.1530-0277.2006.00281.x |
| 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 | |
|---|---|---|---|---|---|---|---|
| D199 | L-alanine | Chemical drug | DB00160 | KYNU | -- | Failed in clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D316 | S-adenosyl-L-methionine | Chemical drug | DB00118 | GNMT cofactor | Antiviral | Under clinical trials | Details |
| D094 | Cysteamine | Chemical drug | DB00847 | GSS stimulant | Renal drug | Under clinical trials | Details |
| D095 | Cysteamine bitartrate | Chemical drug | DB00847 | -- | -- | Under clinical trials | Details |