Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease.
Stanley. Takara L TL; Fourman. Lindsay T LT; Zheng. Isabel I; McClure. Colin M CM; Feldpausch. Meghan N MN; Torriani. Martin M; Corey. Kathleen E KE; Chung. Raymond T RT; Lee. Hang H; Kleiner. David E DE; Hadigan. Colleen M CM; Grinspoon. Steven K SK
Key Findings
- Hepatic IGF‑1 mRNA is lower in people with more liver fat and higher glucose levels
- IGFBP2 and IGFBP4 decrease while IGFBP6, IGFBP7 increase as steatosis worsens
- GHRH treatment raises circulating IGFBP‑1 and IGFBP‑3 but lowers IGFBP‑2 and IGFBP‑6
Practical Outcomes
- Tesamorelin may shift IGFBP patterns toward a profile associated with better glucose handling and less liver fibrosis, offering a potential metabolic benefit for NAFLD. However, evidence is limited to a small HIV cohort, so any self‑experiment should start with low doses, monitor liver enzymes, glucose, and IGFBP levels, and be approached cautiously.
Summary
The study found that lower liver production of IGF‑1 and changes in IGF‑binding proteins (IGFBPs) are linked to worse fatty liver and higher blood sugar. Giving a growth‑hormone‑releasing hormone (GHRH) altered several IGFBPs in the blood, which could affect liver fat and glucose control. This suggests that tesamorelin, a GHRH analog, might influence metabolic health in people with fatty liver, though the data are from a small HIV‑positive group.
Abstract
Growth hormone (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). 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. Analysis of data from a randomized clinical trial of GHRH. Two US academic medical centers. Participants were 61 men and women 18 to 70 years of age with HIV-infection, ≥5% hepatic fat fraction, including 39 with RNA-Seq data from liver biopsy. Hepatic steatosis, inflammation, and fibrosis by histopathology and measures of glucose homeostasis. 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 IGFBPs, IGFBP2 and IGFBP4 were lower and IGFBP6 and IGFBP7 (also known as IGFBP-related protein 1) were higher with increasing steatosis. Hepatic IGFBP6 and IGFBP7 mRNA levels 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. 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.
Study Information
pubmed
2021
2021-01-23T00:00:00.000Z
10.1210/clinem/dgaa792
86
76