Neuroendocrine and genetic aspects of metabolic disturbances in women with simple obesity, polycystic ovary syndrome (PCOS) and eating disorders
Agnieszka Baranowska-Bik1, Wojciech Bik1, Ewa Wolinska-Witort1, Pawel Gaj2, Michal Mikula2, Piotr Bragoszewski2, Jerzy Ostrowski2 & Boguslawa Baranowska1
Neuropeptides and adipocytokines influence metabolic homeostasis and food intake. Deregulation in their secretion leads to insulin resistance or metabolic syndrome. Adiponectin possesses anti-diabetic and insulin sensitizing properties. Expression of this gene remains under control of nuclear peroxisome proliferator-activated receptor (PPAR)-gamma. Ghrelin, an endogenous ligand for GH secratagogue receptor (GHSR), modulates metabolic homeostasis. A high amino-acid homology and transmembrane localization of G-protein coupled receptor 39 (GPR39) and GHSR suggest that ghrelin secretion can be modified by GPR39. Genetic variation found in genomic DNA sequences is a potentially important factor regulating expression level of mentioned genes. We evaluated the role of genetic factors and relationship between metabolic alterations and plasma adiponectin, ghrelin and leptin levels in women with simple obesity, PCOS (non-obese) and anorexia nervosa (AN).
The study consisted of 142 women (109 patients and 33 healthy lean controls) in similar age and was approved by the Local Ethics Committee. For SNP (single nucleotide polymorphism) analyses we genotyped all women for: (PPAR)-gamma, TNF-alpha, GPR39, GHSR, and ADIPOQ. We compared the distribution of alleles according to different clinical course vs. healthy controls. Our main findings are that in lean PCOS women insulin and HOMA-IR were higher comparing to controls but adiponectin and ghrelin did not differ significantly. Furthermore, in AN adiponectin and ghrelin were higher and leptin was lower compared with controls. The correlations between adiponectin, leptin and metabolic parameters were found. Genetic variant correlation was shown only for (PPAR)-gamma (Pro12Ala-rs1801282) locus comparing AN to healthy controls with a preference of higher level of heterozygosity among these patients. Decreased adiponectin and ghrelin levels in obesity cannot be explained by variations loci we examined. We conclude that lean PCOS women show increased insulin resistance. An evidence of genetic correlation of (PPAR)-gamma (Pro12Ala-rs1801282) locus in the group of AN patients was found.