Research Article Details
| Article ID: | A49358 |
| PMID: | 35779256 |
| Source: | J Clin Endocrinol Metab |
| Title: | The GH/IGF-1 axis is associated with intrahepatic lipid content and hepatocellular damage in overweight/obesity. |
| Abstract: | CONTEXT: Obesity is a state of relative growth hormone (GH) deficiency, and GH has been identified as a candidate disease-modifying target in nonalcoholic fatty liver disease (NAFLD) because of its lipolytic and anti-inflammatory properties. However, the GH/IGF-1 axis has not been well characterized in NAFLD. OBJECTIVE: Investigate GH and IGF-1 in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. DESIGN: Cross-sectional. PARTICIPANTS: 102 adults (43% women), 19-67yo, BMI ≥25 kg/m 2, without type 2 diabetes. MEASURES: IHL by magnetic resonance spectroscopy; NAFLD was defined by ≥5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine. Serum IGF-1 (LC/MS). RESULTS: There was no difference in mean age, BMI or sex distribution in NAFLD vs controls. Mean (±SD) IHL was higher in NAFLD vs controls (21.8±13.3% vs 2.9±1.1%, p<0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0±6.3 vs 15.4±11.2 ng/mL, p=0.003), including after controlling for age, sex, visceral adipose tissue and fasting glucose. In a stepwise model, peak-stimulated GH predicted 14.6% of the variability in IHL (p=0.004). Higher peak-stimulated GH was also associated with lower ALT. Higher IGF-1 was associated with lower risk of liver fibrosis by Fibrosis-4 scores. CONCLUSIONS: Individuals with NAFLD have lower peak-stimulated GH but similar IGF-1 levels versus controls. Higher peak-stimulated GH is associated with lower IHL and less hepatocellular damage. Higher IGF-1 is associated with more favorable fibrosis risk scores. These data implicate GH and IGF-1 as potential disease modifiers in the development and progression of NAFLD. |
| DOI: | 10.1210/clinem/dgac405 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D160 | Growth Hormone | Biological drug | DB00052 | GHR ligand; PRLR ligand | -- | Under clinical trials | Details |
| D328 | Serine | Chemical drug | DB00133 | SRR | Improve insulin resistance | Under clinical trials | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D343 | Somatropin | Biological drug | DB00052 | GHR ligand; PRLR ligand | Hormone replacement drug | 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 |