Research Article Details
| Article ID: | A22400 |
| PMID: | 24616207 |
| Source: | Obesity (Silver Spring) |
| Title: | Macrophages and fibrosis in adipose tissue are linked to liver damage and metabolic risk in obese children. |
| Abstract: | OBJECTIVE: Obesity in childhood is associated with an inflammatory state in adipose tissue and liver, which elevates risk for diabetes and liver disease. No prior study has examined associations between pathologies occurring in adipose tissue and liver to identify elements of tissue damage associated with type 2 diabetes risk. This study sought to determine whether inflammation and fibrosis in abdominal subcutaneous adipose tissue (SAT) in obese/overweight children (BMI-z 2.3 ± 0.76) was related to the extent of observed liver disease or type 2 diabetes risk. METHODS: Biopsy samples of abdominal (SAT) and liver were simultaneously collected from 33 Italian children (mean BMI 28.1 ± 5.1 kg/m(2) and mean age 11.6 ± 2.2 years) with confirmed NAFLD. Histology and immunohistochemistry were conducted on biopsies to assess inflammation and fibrosis in adipose tissue and fibrosis and inflammation in liver. RESULTS: Presence vs. absence of crown-like structures (CLS) in SAT was significantly related to liver fibrosis scores (1.7 ± 0.7 vs. 1.2 ± 0.7, P = 0.04) independent of BMI. SAT fibrosis was significantly correlated with a lower disposition index (r = -0.48, P = 0.006). No other adipose measures were associated with liver disease parameters. CONCLUSION: Markers of subcutaneous white adipose tissue inflammation are associated with greater extent of liver fibrosis independent of obesity and SAT fibrosis may contribute to diabetes risk through reduced insulin secretion. |
| DOI: | 10.1002/oby.20730 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| 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 |
| 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 |