Association of metabolites with obesity based on two gene variants, MC4R rs17782313 and BDNF rs6265

Biochim Biophys Acta Mol Basis Dis. 2021 Jul 1;1867(7):166144. doi: 10.1016/j.bbadis.2021.166144. Epub 2021 Apr 14.

Abstract

Previous genome-wide association analyses for obesity related genes demonstrated the association of BDNF gene variant rs6265 and MC4R gene variant rs17782313 with body mass index (BMI). However, the associated metabolite pathways are still behind the curtain. The aim of the current study is to investigate the associations of metabolic changes in obesity with MC4R gene variant rs17782313 and BDNF variant rs6265. Gas chromatography-mass spectrometry based untargeted metabolomics approach was used and 42 identified serum metabolites were selected for statistical analyses. Significant association of seven metabolites with MC4R gene variant rs17782313 based on obesity and thirty metabolites with obesity dependent BDNF variant rs6265 using additive model (adjusted p < 0.05) was observed. This study highlights the importance of alteration of fatty acid biosynthesis, probably due to high consumption of fats may cause to develop obesity. But obesity is a complex disorder and the full clarification of this complex machinery is still distant. To understand the obesity in a better way, more studies are required to identify remaining metabolites and also mechanism of these metabolic entities.

Keywords: BDNF; Gas chromatography-mass spectrometry; MC4R; Metabolite-GWAS; Obesity.

MeSH terms

  • Adolescent
  • Adult
  • Body Mass Index*
  • Brain-Derived Neurotrophic Factor / genetics*
  • Case-Control Studies
  • Child
  • Female
  • Genetic Predisposition to Disease*
  • Genome-Wide Association Study
  • Genotype
  • Humans
  • Male
  • Metabolome*
  • Middle Aged
  • Obesity / etiology
  • Obesity / metabolism
  • Obesity / pathology*
  • Polymorphism, Single Nucleotide*
  • Prognosis
  • Receptor, Melanocortin, Type 4 / genetics*
  • Risk Factors
  • Young Adult

Substances

  • Brain-Derived Neurotrophic Factor
  • MC4R protein, human
  • Receptor, Melanocortin, Type 4
  • BDNF protein, human