Cyclic glycine-proline administration normalizes high-fat diet-induced synaptophysin expression in obese rats

Neuropeptides. 2019 Aug:76:101935. doi: 10.1016/j.npep.2019.05.006. Epub 2019 May 22.

Abstract

Childhood metabolic disorders are associated with insulin-like growth factor (IGF)-1 deficiency, which can adversely affect brain development and function. As a neuropeptide, cyclic glycine-proline (cGP) improves IGF-1 function in brain and regulates IGF-1 bioavailability in plasma. Whether such a regulatory process mediates the neurotrophic effects of cGP remains unknown. This study examined the effects cGP treatment on synaptic expression and their association with IGF-1, IGF binding protein (IGFBP)-2 and cGP concentrations in the brain of rats with high fat diet (HFD)-induced obesity. Male rats received either a HFD or a standard chow diet (STD) from weaning and were then treated with either saline or cGP from 11 to 15 weeks of age. The concentrations of cGP, IGF-1 and IGFBP-2 were measured in the brain tissues using ELISA and HPLC-MS. The expressions of synaptic markers were evaluated in the hippocampus, hypothalamus and striatum using immunohistochemical staining. Compared to the STD group, IGF-1 and IGFBP-2, but not cGP concentrations, were lower in the HFD groups. The expression of hippocampal synaptophysin, glutamate receptor-1, GFAP and striatal tyrosine-hydroxylase were also reduced in the HFD groups. While treatment did not alter tissue IGF-1, cGP administration that increased the concentration of cGP in brain tissues, normalized the expression of synaptophysin, GFAP and tyrosine-hydroxylase, but not glutamate receptor-1. IGF-1 concentration in brain tissues correlated with the expression of all synaptic markers. HFD feeding reduced synaptic expression and tissue IGF-1 in brains which were closely associated, thus suggesting IGF-1 in the brain is largely bioavailable. Without increasing IGF-1 in the brain, administration of cGP normalized synaptic expression, possibly be mediated through increasing bioavailable IGF-1, but further studies are required to confirm this.

Keywords: Autocrine regulation; Cyclic glycine-proline (cGP); Expression of synaptic markers; IGF binding protein (IGFBP)-2; Insulin-like growth factor-1 (IGF-1).

MeSH terms

  • Animals
  • Diet, High-Fat
  • Disease Models, Animal
  • Insulin-Like Growth Factor I / metabolism
  • Male
  • Obesity / metabolism*
  • Peptides, Cyclic / administration & dosage*
  • Rats, Sprague-Dawley
  • Synaptophysin / metabolism*

Substances

  • Peptides, Cyclic
  • Synaptophysin
  • Syp protein, rat
  • cyclic glycine-proline
  • insulin-like growth factor-1, rat
  • Insulin-Like Growth Factor I