Research Article Details
| Article ID: | A25086 |
| PMID: | 22183689 |
| Source: | Hepatology |
| Title: | Effect of adipose tissue insulin resistance on metabolic parameters and liver histology in obese patients with nonalcoholic fatty liver disease. |
| Abstract: | UNLABELLED: The role of adipose tissue insulin resistance in the pathogenesis of nonalcoholic fatty liver disease (NAFLD) remains unclear. To evaluate this, we measured in 207 patients with NAFLD (age = 51 ± 1, body mass index = 34.1 ± 0.3 kg/m(2) ) and 22 controls without NAFLD (no NAFLD) adipose tissue insulin resistance by means of a validated index (Adipo-IR(i) = plasma free fatty acids [FFA] x insulin [FPI] concentration) and as the suppression of plasma FFA during an oral glucose tolerance test and by a low-dose insulin infusion. We also explored the relationship between adipose tissue insulin resistance with metabolic and histological parameters by dividing them based on quartiles of adipose tissue insulin resistance (Adipo-IR(i) quartiles: Q1 = more sensitive; Q4 = more insulin resistant). Hepatic insulin resistance, measured as an index derived from endogenous glucose production x FPI (HIRi), and muscle insulin sensitivity, were assessed during a euglycemic insulin clamp with 3-[(3) H] glucose. Liver fat was measured by magnetic resonance imaging and spectroscopy, and a liver biopsy was performed to assess liver histology. Compared to patients without steatosis, patients with NAFLD were insulin resistant at the level of adipose tissue, liver, and skeletal muscle and had higher plasma aspartate aminotransferase and alanine aminotransferase, triglycerides, and lower high-density lipoprotein cholesterol and adiponectin levels (all P < 0.01). Metabolic parameters, hepatic insulin resistance, and liver fibrosis (but not necroinflammation) deteriorated as quartiles of adipose tissue insulin resistance worsened (all P < 0.01). CONCLUSION: Adipose tissue insulin resistance plays a key role in the development of metabolic and histological abnormalities of obese patients with NAFLD. Treatment strategies targeting adipose tissue insulin resistance (e.g., weight loss and thiazolidinediones) may be of value in this population. |
| DOI: | 10.1002/hep.25539 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 |
| 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 |
| D366 | Thiazolidinediones | Chemical drug | DB11898 | -- | -- | Under clinical trials | Details |
| D083 | CLA | Chemical drug | DB01211 | KCNH2; SLCO1B1; SLCO1B3 | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | 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 |