Relationship of IGF-1 and IGF-Binding Proteins to Disease Severity and Glycemia in Nonalcoholic Fatty Liver Disease

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.

Exosomal miR-486-5p derived from human placental microvascular endothelial cells regulates proliferation and invasion of trophoblasts via targeting IGF1

“…## P < 0.01 compared to H/R-exo. ^^P < 0.01 compared to (H/R + NC inhibitor)-exo in some diseases [30][31][32]. Previous research found that IGF1 overexpression may promote the migration of trophoblast cells [24].…”

Hepatocrinology

“…Serum IGF-1 levels are decreased in cirrhosis as the synthetic capacity of the liver is diminished [ 18 , 19 ]. Hepatic IGF-1 production is also lower in those with higher degrees of steatosis, non-alcoholic fatty liver disease (NAFLD) activity score (NAS), and hepatic fibrosis [ 20 , 21 ]. Conversely, NAFLD occurs more commonly in adult GHD.…”

La Non-Alcoholic Fatty Liver Disease, una patologia epatica di interesse endocrinologico

“…Il GH influenza fisiologicamente il metabolismo glico-lipidico, promuovendo la lipolisi, la glicolisi e la gluconeogenesi, ma è altresì responsabile di un aumento dell’insulino-resistenza. Dati recenti suggeriscono una forte associazione tra i livelli epatici di IGF-1 e alcune proteine leganti l’IGF e il grado di steatosi epatica [ 15 ]. L’associazione tra il deficit di secrezione dell’ormone della crescita nell’adulto (GHD) e la steatosi epatica non è ancora completamente chiarita.…”

“…2 Fattori che contribuiscono alla genesi della steatosi epatica. FFA, acidi grassi liberi associazione tra i livelli epatici di IGF-1 e alcune proteine leganti l'IGF e il grado di steatosi epatica [15]. L'associazione tra il deficit di secrezione dell'ormone della crescita nell'adulto (GHD) e la steatosi epatica non è ancora completamente chiarita.…”