Influence of Single-Nucleotide Polymorphisms in PPAR-δ, PPAR-γ, and PRKAA2 on the Changes in Anthropometric Indices and Blood Measurements through Exercise-Centered Lifestyle Intervention in Japanese Middle-Aged Men.

Yuichiro Nishida,Chisato Shimanoe,Megumi Hara,Minako Iyadomi,Mikako Horita,Hiroaki Tanaka,Keitaro Tanaka,Yasuki Higaki,Hiroaki Taniguchi,Hirotaka Tominaga

doi:10.3390/ijms19030703

Abstract

The purpose of the current study was to examine the influence of single-nucleotide polymorphisms (SNPs) in the peroxisome proliferator-activated receptor-δ (PPAR-δ), PPAR-γ, and α2 isoforms of the catalytic subunit of AMP-activated protein kinase (PRKAA2) on the extent of changes in anthropometric indices and blood measurements through exercise-centered lifestyle intervention in middle-aged men. A total of 109 Japanese middle-aged male subjects (47.0 ± 0.4 years) participated in the baseline health checkup, 6-month exercise-centered lifestyle intervention, and second checkup conducted several months after the subject completed the intervention. The body mass index (BMI), waist circumference, and clinical measurements, including hemoglobin Alc (HbA1c), triglyceride (TG), alanine aminotransferase (ALT), and γ-glutamyl-transpeptidase (γ-GTP), were measured at the baseline and second checkup. The three SNPs of PPAR-δ A/G (rs2267668), PPAR-γ C/G (rs1801282), and PRKAA2 A/G (rs1418442) were determined. Blunted responses in the reduction in the BMI and waist circumference were observed in A/A carriers of PPAR-δ SNP compared with G allele carriers (all p < 0.05). The A/A carriers also displayed less-marked improvements in HbA1c, TG, ALT, and γ-GTP (all p < 0.05). The current results suggest that A/A carriers of PPAR-δ SNP (rs2267668) may enjoy fewer beneficial effects of exercise-centered lifestyle intervention on anthropometric indices and blood measurements.

Highlights

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that play an important role in obesity and metabolism [1,2]
The genotype distributions of the three single-nucleotide polymorphisms (SNPs), peroxisome proliferator-activated receptor-δ (PPAR-δ) A/G, PPAR-γ C/G, and PRKAA2 A/G in the current participants did not deviate from the Hardy-Weinberg equilibrium (p > 0.05)
Multiple linear regression analyses showed that the associations of the PPAR-δ SNP with the changes in HbA1c (p = 0.26) and ALT (p = 0.31) were attenuated, being statistically insignificant, whereas the associations of the PPAR-δ SNP with the changes in TG (p = 0.02) and γ-GTP (p = 0.04) remained significant even after adjustment for the change in body weight (Table 3)

Summary

Introduction

Peroxisome proliferator-activated receptors (PPARs) are nuclear receptors that play an important role in obesity and metabolism [1,2]. While PPAR-α and PPAR-γ are preferentially expressed in liver and adipose tissue, respectively [1], PPAR-δ is ubiquitously expressed throughout the body, and its expression is especially high in skeletal muscle compared with the other two isoforms [3,4] These three PPAR isoforms together control various aspects of fatty acid metabolism, energy balance, insulin sensitivity, and glucose homeostasis through their coordinated activities in adipose tissue, liver, and skeletal muscle [1]. Another key molecule in lipid and glucose metabolism as well as exercise adaptation is AMP-activated protein kinase (AMPK). While no defects in glucose homoeostasis were observed in AMPK α1 knockout mice, AMPK α2 knockout mice were insulin-resistant [6]

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