Genetic Variants in the Activation of the Brown-Like Adipocyte Pathway and the Risk for Severe Obesity

Abstract

Background: Regular physical activity has an important role in energy expenditure and combats the development of obesity. During exercise, PPARGC1A is overexpressed, stimulating an increase of the expression of FNDC5. This protein is cleaved to release the hormone irisin, which activates a browning process in white adipose tissue through an increase in UCP1 expression. As a result, irisin leads to mitochondrial heat production and energy expenditure. Objectives: The aim of this study was to investigate whether genetic variants in genes related to browning are associated with severe obesity and obesity-related features. This case-control study comprised 210 individuals with severe obesity (median body mass index [BMI] 45.6 [range 40.5-52.2]) and 191 normal-weight subjects ). Methods: Genomic DNA was extracted from peripheral blood and the genotypes of the PPARGC1A (rs8192678, rs3736265, rs2970847, and rs3755863) and UCP1 (rs6536991 and rs12502572) genes were obtained using Taqman ® assay. For the FNDC5 gene, screening of exons 3-5 as well as their intron-exon boundaries was performed using automatic sequencing. Results: Our results demonstrated that PPARGC1A rs2970847 and UCP1 rs12502572 are associated with severe obesity. Furthermore, these polymorphisms influence anthropometric traits, such as BMI, body weight, and body adiposity index. Our findings also showed a dose-effect relationship between PPARGC1A rs8192678 and fasting plasma glucose. Finally, 5 rare mutations were identified in FNDC5, and 1 of these is a novel missense mutation. Conclusion: This study shows that genetic variants in the activation of brown-like adipocyte pathway play an important role in the susceptibility to severe obesity.

Association of Genetic Variant in MC4R (rs17782313) Gene with Obesity and Other Health Behaviors among Selected Bangladeshi Population: A Population-based Case-control Study

“…al. also found a higher value of anthropometric and biochemical parameters in obese people than in normal [30]. Another study conducted by Luying Gao et.…”