학술논문
The GH/IGF-1 Axis Is Associated With Intrahepatic Lipid Content and Hepatocellular Damage in Overweight/Obesity
Document Type
Academic Journal
Author
Source
Journal of Clinical Endocrinology & Metabolism. September 2022, Vol. 107 Issue 9, pe3624, 9 p.
Subject
Language
English
ISSN
0021-972X
Abstract
Nonalcoholic fatty liver disease (NAFLD), fatty infiltration of the liver in the absence of alcohol use, is a prevalent and serious complication of obesity (1). However, the mechanisms responsible for [...]
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: We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. Methods: This cross-sectional study included 102 adults (43% women; age 19-67; BMI [greater than or equal to] 25 kg/[m.sup.2]) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by [greater than or equal to] 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS). Results: There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean ([+ or -] SD) IHL was higher in NAFLD vs controls (21.8 [+ or -] 13.3% vs 2.9 [+ or -] 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 [+ or -] 6.3 vs 15.4 [+ or -] 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 serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. Conclusion: Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are 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. Key Words: growth hormone, insulin-like growth factor-1, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis Abbreviations: ALT, alanine aminotransferase; BMI, body mass index; CT, computed tomography; FIB-4, Fibrosis-4 score; GH, growth hormone; GHRH, growth hormone--releasing hormone; [.sup.1]H-MRS, proton magnetic resonance spectroscopy; HbA1c, glycated hemoglobin; HSC, hepatic stellate cell; IGF-1, insulin-like growth factor 1; IHL, intrahepatic lipid content; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.
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: We aimed to investigate serum GH and IGF-1 levels in relation to intrahepatic lipid content (IHL) and markers of hepatocellular damage and fibrosis in NAFLD. Methods: This cross-sectional study included 102 adults (43% women; age 19-67; BMI [greater than or equal to] 25 kg/[m.sup.2]) without type 2 diabetes. IHL was measured by magnetic resonance spectroscopy; NAFLD was defined by [greater than or equal to] 5% IHL. Peak-stimulated GH in response to GH releasing hormone and arginine was assessed as was serum IGF-1 (LC/MS). Results: There was no difference in mean age, BMI, or sex distribution in NAFLD vs controls. Mean ([+ or -] SD) IHL was higher in NAFLD vs controls (21.8 [+ or -] 13.3% vs 2.9 [+ or -] 1.1%, P < 0.0001). Mean peak-stimulated GH was lower in NAFLD vs controls (9.0 [+ or -] 6.3 vs 15.4 [+ or -] 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 serum IGF-1 levels were associated with lower risk of liver fibrosis by Fibrosis-4 scores. Conclusion: Individuals with NAFLD have lower peak-stimulated GH levels but similar IGF-1 levels as compared to controls. Higher peak-stimulated GH levels are associated with lower IHL and less hepatocellular damage. Higher IGF-1 levels are 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. Key Words: growth hormone, insulin-like growth factor-1, nonalcoholic fatty liver disease, nonalcoholic steatohepatitis Abbreviations: ALT, alanine aminotransferase; BMI, body mass index; CT, computed tomography; FIB-4, Fibrosis-4 score; GH, growth hormone; GHRH, growth hormone--releasing hormone; [.sup.1]H-MRS, proton magnetic resonance spectroscopy; HbA1c, glycated hemoglobin; HSC, hepatic stellate cell; IGF-1, insulin-like growth factor 1; IHL, intrahepatic lipid content; NAFLD, nonalcoholic fatty liver disease; NASH, nonalcoholic steatohepatitis.