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Abstract Details
Relationship of IGF-1 and IGF Binding Proteins to Disease Severity and Glycemia in Non-Alcoholic Fatty Liver Disease
J Clin Endocrinol Metab. 2020 Oct 30;dgaa792. doi: 10.1210/clinem/dgaa792.Online ahead of print.
Takara L Stanley1, Lindsay T Fourman1, Isabel Zheng1, Colin M McClure1, Meghan N Feldpausch1, Martin Torriani2, Kathleen E Corey3, Raymond T Chung3, Hang Lee4, David E Kleiner5, Colleen M Hadigan6, Steven K Grinspoon1
Author information
1Metabolism Unit, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
2Department of Radiology, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
3Liver Center, Gastroenterology Division, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
4Biostatistics Center, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA.
5Laboratory of Pathology, Center for Cancer Research, National Cancer Institute, Bethesda, MD, USA.
6National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, MD, USA.
Abstract
Context: GH and IGF-1 help regulate hepatic glucose and lipid metabolism, and reductions in these hormones may contribute to development of nonalcoholic fatty liver disease (NAFLD).
Objective: To assess relationships between hepatic expression of IGF1 and IGF binding proteins (IGFBPs) and measures of glycemia and liver disease in adults with NAFLD. Secondarily to assess effects of GH releasing hormone (GHRH) on circulating IGFBPs.
Design: Analysis of data from a randomized clinical trial of GHRH.
Setting: Two US academic medical centers.
Participants: 61 men and women 18-70yo with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy.
Main outcome measures: Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis.
Results: Hepatic IGF1 mRNA was significantly lower in individuals with higher steatosis and NAFLD Activity Score (NAS) and was inversely related to glucose parameters, independent of circulating IGF-1. Among the IGFBP's, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA were positively associated with NAS. IGFBP7 mRNA increased with increasing fibrosis. Hepatic IGFBP1 mRNA was inversely associated with glycemia and insulin resistance, with opposite relationships present for IGFBP3 and IGFBP7. GHRH increased circulating IGFBP-1 and IGFBP-3, but decreased IGFBP-2 and IGFBP-6.
Conclusions: These data demonstrate novel relationships of IGF-1 and IGFBPs with NAFLD severity and glucose control, with divergent roles seen for different IGFBPs. Moreover, the data provide new information on the complex effects of GHRH on IGFBPs.