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.

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.

Association between the PPARGC1A polymorphism and aerobic capacity in Japanese middle-aged men.

OBJECTIVE: A lower frequency for the peroxisome proliferator-activated receptor γ coactivator 1α (PPARGC1A) Ser482 allele has been reported in elite-level endurance athletes among Caucasians, although this gene polymorphism has not been found to be associated with aerobic capacity in German, Dutch or Chinese populations. The purpose of the current study was to examine the associations between the Gly482Ser polymorphism and aerobic fitness in 112 Japanese middle-aged men. METHODS: The PPARGC1A Gly482Ser polymorphism was identified according to a TaqMan(®) SNP genotyping assay. Habitual physical activity was objectively measured using an accelerometer. The lactate threshold (LT), an index of aerobic fitness, was measured based on a submaximal graded exercise test performed on an electric cycle ergometer. The association between the LT and the Gly482Ser polymorphism was assessed according to a multiple regression analysis and analysis of covariance, with adjustment for potential confounders (age, body mass index, cigarette smoking, physical activity level and regular exercise). RESULTS: A significant association was observed between the PPARGC1A Gly482Ser polymorphism and LT, as carriers of the Ser482 had higher LT values than the Gly482 carriers. CONCLUSION: The current results suggest that the PPARGC1A Ser482 allele is associated with a higher aerobic capacity in Japanese middle-aged men.

Influence of physical activity intensity and aerobic fitness on the anthropometric index and serum uric acid concentration in people with obesity.

BACKGROUND AND OBJECTIVE: Physical activity (PA) is considered an important approach to prevent and treat obesity and hyperuricemia. The purpose of the present study was to examine the influence of PA intensity and aerobic fitness on anthropometric indices and serum uric acid in obese individuals. METHODS: PA was examined using a single-axial accelerometer and aerobic fitness was assessed by electric cycle ergometry in obese middle-aged men (n=71, 47.2 ± 4.4 years). PA was defined as light (<3 metabolic equivalents [METs]), moderate (3.0-6.0 METs) or vigorous (>6.0 METs) intensity from the corresponding METs multiplied by time spent at the corresponding intensity levels. Serum uric acid was measured by the uricase peroxidase method. RESULTS: The association between aerobic fitness index (lactate threshold) and serum uric acid did not reach statistical significance after adjustment for potential confounding factors (age, body mass index [BMI], and alcohol consumption) (ß=-0.110, p=0.138). Light intensity PA was inversely associated with BMI and waist circumference, even after adjustment for age and alcohol consumption (BMI: ß=-0.543, p=0.023; waist circumference: ß=-1.333, p=0.016). Moderate intensity PA, but not light or vigorous intensity PA, was inversely correlated with the uric acid level and this remained significant after adjustment for age, BMI, and alcohol consumption (ß=-0.222, p=0.036). CONCLUSION: Our results suggest that light intensity PA may have an important role in weight control while moderate intensity PA may be associated with the lower uric acid concentrations in obese individuals.

Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn.

Intrathecal administration of baclofen, a GABA(B)-receptor agonist, affects pain behavior induced by formalin in a biphasic manner; baclofen at low doses enhances pain while producing antinociception at high doses. This may be due to the fact that baclofen modulates each of excitatory and inhibitory transmission in the dorsal horn of the spinal cord with a distinct sensitivity, resulting in a biphasic action on pain transmission. To address this issue, we examined the actions of baclofen on miniature excitatory (glutamatergic) and inhibitory (GABAergic) postsynaptic currents (mEPSCs and mIPSCs, respectively) in substantia gelatinosa (SG) neurons of adult rat spinal cord slices by using the whole-cell voltage-clamp technique. Baclofen reduced the frequency of both mEPSC and mIPSC without a change in their amplitudes. These actions were dose-dependent in a concentration range of 0.1-100 microM; the effective concentrations for the half-inhibition of mEPSC and mIPSC frequency were 4.44+/-0. 60 microM (n=7) and 4.31+/-0.77 microM (n=6), respectively. These results indicate that each of glutamatergic and GABAergic nerve terminals in the SG is endowed with the GABA(B) receptor, the activation of which depresses the release of neurotransmitter from the terminal; this provides a cellular basis for the modulation of pain by baclofen. It is suggested from a similar affinity for baclofen of the GABA(B) receptors on both terminals that the baclofen-induced biphasic action on pain behaviors cannot be accounted for by only its presynaptic actions in the SG and that other actions such as an inhibitory action of baclofen on postsynaptic neurons also have to be taken into consideration.