Research Article Details
| Article ID: | A04141 |
| PMID: | 33743554 |
| Source: | Hepatology |
| Title: | Increased Adipose Tissue Fibrogenesis, Not Impaired Expandability, Is Associated With Nonalcoholic Fatty Liver Disease. |
| Abstract: | BACKGROUND AND AIMS: It is proposed that impaired expansion of subcutaneous adipose tissue (SAT) and an increase in adipose tissue (AT) fibrosis causes ectopic lipid accumulation, insulin resistance (IR), and metabolically unhealthy obesity. We therefore evaluated whether a decrease in SAT expandability, assessed by measuring SAT lipogenesis (triglyceride [TG] production), and an increase in SAT fibrogenesis (collagen production) are associated with NAFLD and IR in persons with obesity. APPROACH AND RESULTS: In vivo abdominal SAT lipogenesis and fibrogenesis, expression of SAT genes involved in extracellular matrix (ECM) formation, and insulin sensitivity were assessed in three groups of participants stratified by adiposity and intrahepatic TG (IHTG) content: (1) healthy lean with normal IHTG content (Lean-NL; n = 12); (2) obese with normal IHTG content and normal glucose tolerance (Ob-NL; n = 25); and (3) obese with NAFLD and abnormal glucose metabolism (Ob-NAFLD; n = 25). Abdominal SAT TG synthesis rates were greater (P < 0.05) in both the Ob-NL (65.9 ± 4.6 g/wk) and Ob-NAFLD groups (71.1 ± 6.7 g/wk) than the Lean-NL group (16.2 ± 2.8 g/wk) without a difference between the Ob-NL and Ob-NAFLD groups. Abdominal SAT collagen synthesis rate and the composite expression of genes encoding collagens progressively increased from the Lean-NL to the Ob-NL to the Ob-NAFLD groups and were greater in the Ob-NAFLD than the Ob-NL group (P < 0.05). Composite expression of collagen genes was inversely correlated with both hepatic and whole-body insulin sensitivity (P < 0.001). CONCLUSIONS: AT expandability is not impaired in persons with obesity and NAFLD. However, SAT fibrogenesis is greater in persons with obesity and NAFLD than in those with obesity and normal IHTG content, and is inversely correlated with both hepatic and whole-body insulin sensitivity. |
| DOI: | 10.1002/hep.31822 |
| 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 | |
|---|---|---|---|---|---|---|---|
| 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 |