Associations of GHR, IGF-1 and IGFBP-3 expression in adipose tissue cells with obesity-related alterations in corresponding circulating levels and adipose tissue function in children

Adipocyte. 2022 Dec;11(1):630-642. doi: 10.1080/21623945.2022.2148886.

Abstract

Components of the growth hormone (GH) axis, such as insulin-like growth factor-1 (IGF-1), IGF-1 binding protein-3 (IGFBP-3), GH receptor (GHR) and GH-binding protein (GHBP), regulate growth and metabolic pathways. Here, we asked if serum levels of these factors are altered with overweight/obesity and if this is related to adipose tissue (AT) expression and/or increased fat mass. Furthermore, we hypothesized that expression of GHR, IGF-1 and IGFBP-3 is associated with AT function. Serum GHBP levels were increased in children with overweight/obesity throughout childhood, while for IGF-1 levels and the IGF-1/IGFBP-3 molar ratio obesity-related elevations were detectable until early puberty. Circulating levels did not correlate with AT expression of these factors, which was decreased with overweight/obesity. Independent from obesity, expression of GHR, IGF-1 and IGFBP-3 was related to AT dysfunction,and increased insulin levels. Serum GHBP was associated with liver fat percentage and transaminase levels. We conclude that obesity-related elevations in serum GHBP and IGF-1 are unlikely to be caused by increased AT mass and elevations in GHBP are more closely related to liver status in children. The diminished AT expression of these factors with childhood obesity may contribute to early AT dysfunction and a deterioration of the metabolic state.

Trial registration: ClinicalTrials.gov NCT02208141 NCT01605123.

Keywords: GHBP; GHR; IGF-1; IGFBP-3; Obesity; adipose tissue; childhood obesity; children; growth hormone; liver fat.

MeSH terms

  • Adipose Tissue / metabolism
  • Child
  • Humans
  • Insulin-Like Growth Factor Binding Protein 3*
  • Insulin-Like Growth Factor I / metabolism
  • Overweight
  • Pediatric Obesity*

Substances

  • Insulin-Like Growth Factor Binding Protein 3
  • Insulin-Like Growth Factor I
  • somatotropin-binding protein

Associated data

  • ClinicalTrials.gov/NCT02208141
  • ClinicalTrials.gov/NCT01605123

Grants and funding

This work was supported by the German Research Foundation (DFG) for the Clinical Research Center ‘Obesity Mechanisms’ SFB1052/CRC1052 (No 209933838) project C05 to AK, the Integrated Research and Treatment Center Adiposity Diseases funded by the German Federal Ministry of Education and Research (Grant 01EO1501), and the German Diabetes Association (DDG). JS was supported by European Society for Pediatric Endocrinology (ESPE) Research Fellowship. EK was supported by ESPE Early Career Scientific Development Grant. The funders of the study had no role in study design, data collection, data analysis, data interpretation, or writing of the report.