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Taniguchi H.,Waseda University | Tanisawa K.,Waseda University | Tanisawa K.,Japan Society for the Promotion of Science | Sun X.,Waseda University | And 3 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2016

Context: Age-related hepatic fat accumulation increases the risk of cardiometabolic diseases, and the fibroblast growth factor (FGF) 21â€"resistant state caused by fatty liver underlies the pathogenesis of these diseases. Objective: Previous studies suggested that a higher level of cardiorespiratory fitness was associated with both lower hepatic fat contentandserum FGF21 levels; however, the effect of endurance exercise on hepatic fat content and serum FGF21 concentration has not been studied. Therefore, we aimed to elucidate whether endurance exercise reduced hepatic fat content and serum FGF21 levels. Design: This is a randomized crossover trial. Setting: The study setting was an institutional practice. Patients: Thirty-three elderly Japanese men participated in the study. Intervention: The intervention was a 5-week endurance exercise program comprising three cycle ergometer sessions per week. Main Outcome Measures: Hepatic fat content was assessed by proton magnetic resonance spectroscopy, and serum FGF21 level was determined by ELISA. Results:A5-week endurance exercise program decreased the hepatic fat content and serum FGF21 levels without weight loss, and the changes were higher in the exercise period than in the control period (P=.021andP=.026, respectively). Correlation analysis demonstrated that only the change in hepatic fat content was significantly and positively correlated with change in serum FGF21 levels (r = 0.366, P = .006). Conclusions: A 5-week endurance exercise program decreased hepatic fat content and serum FGF21 levels without weight loss in elderly men, and exercise-induced hepatic fat reduction mediated the reduction in serum FGF21 levels. These findings suggest that endurance exercise modulates hepatic fat content and FGF21 resistance, regardless of obesity status. Copyright © 2016 by the Endocrine Society. Source

Tanisawa K.,Waseda University | Taniguchi H.,Waseda University | Sun X.,Waseda University | Ito T.,Waseda University | And 5 more authors.
Metabolism: Clinical and Experimental | Year: 2014

Objective This cross-sectional study analyzed the association of serum irisin concentrations with cardiorespiratory fitness levels and common single nucleotide polymorphisms (SNPs) in the FNDC5 gene and examined the relationships between cardiorespiratory fitness levels, common SNPs in FNDC5, and glucose metabolism. Materials/Methods Cardiorespiratory fitness was assessed by measuring peak oxygen uptake (VO2peak) and serum irisin levels by ELISA in 163 Japanese men (age, 21-79 years). Subjects were divided into low- and high-fitness groups within each age group according to the median VO 2peak value. Common SNPs (rs3480 and rs16835198) of the FNDC5 gene were genotyped with the TaqMan assay. Glucose metabolism was evaluated by measuring HbA1c, fasting plasma glucose (FPG), insulin levels, and HOMA-IR. Results Serum irisin levels were negatively correlated with age (p < 0.001) and not associated with the VO2peak or HOMA-IR. In the low-fitness group, SNP analysis revealed that subjects with the rs3480 AG and GG genotypes had higher levels of insulin and HOMA-IR than those with the AA genotype (p < 0.01; no significant difference was observed in the high-fitness group). The GG genotypes of rs16835198 were associated with increased HbA1c and FPG in the low-fitness group only (p < 0.05). SNPs and both fitness groups were not associated with serum irisin levels. Conclusions In Japanese men, cardiorespiratory fitness levels and common SNPs in FNDC5 are not associated with circulating irisin levels, whereas high cardiorespiratory fitness abolishes the association between the rs3480 and rs16835198 SNPs and glucose metabolism independent of serum irisin levels. © 2014 Elsevier Inc. Source

Tanisawa K.,Waseda University | Tanisawa K.,Tokyo Metropolitan University | Ito T.,Waseda University | Sun X.,Waseda University | And 6 more authors.
Physiological Genomics | Year: 2014

High cardiorespiratory fitness (CRF) is associated with a reduced risk for dyslipidemia; however, blood lipid levels are also affected by individual genetic variations. We performed a cross-sectional study to determine whether CRF modifies polygenic risk for dyslipidemia. Serum levels of triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C) were measured in 170 Japanese men (age 20-79 yr). CRF was assessed by measuring maximal oxygen uptake (VO2max), and subjects were divided into low-fitness and high-fitness groups according to the reference VO2max value for health promotion in Japan. We analyzed 19 single nucleotide polymorphisms (SNPs) associated with TG, LDL-C, or HDL-C levels. Based on these SNPs, we calculated three genetic risk scores (GRSs: TG-GRS, LDL-GRS, and HDL-GRS), and subjects were divided into low, middle, and high groups according to the tertile for each GRS. Serum TG levels of low-fitness individuals were higher in the high and middle TG-GRS groups than in the low TG-GRS group (P < 0.01 and P < 0.05, respectively), whereas no differences were detected in the TG levels of high-fitness individuals among the TG-GRS groups. In contrast, the high LDL-GRS group had higher LDL-C levels than did the low LDL-GRS group, and HDL-C levels were lower in the high HDL-GRS group than in the low HDL-GRS group regardless of the fitness level (P < 0.05). These results suggest that high CRF attenuates polygenic risk for hypertriglyceridemia; however, high CRF may not modify the polygenic risk associated with high LDL-C and low HDL-C levels in Japanese men. © 2014 the American Physiological Society. Source

Taniguchi H.,Waseda University | Tanisawa K.,Waseda University | Sun X.,Waseda University | Cao Z.-B.,Waseda University | And 6 more authors.
Journal of Clinical Endocrinology and Metabolism | Year: 2014

Context: Fibroblast growth factor-21 (FGF21) is an important metabolic regulator suggested to improve glucose metabolism and prevent dyslipidemia. An FGF21-resistant state that increases circulating FGF21 has been reported in obese patients. Although regular exercise prevents metabolic disease, the relationship of the fitness level to serum FGF21 level and body fat distribution in humans remains poorly understood.Objective: The objective of the study was to determine the relationship among the serum FGF21 concentration, cardiorespiratory fitness (CRF) level, and visceral fat area (VFA).Design: Serum FGF21 was measured by an ELISA in 166 middle-aged and elderly Japanese men (aged 30-79 y) and 25 untrained and 21 endurance-trained young men (aged 19-29y). CRF was assessed by measuring the peak oxygen uptake (VO2peak) and VFA by magnetic resonance imaging.Results: In the middle-aged and elderly subjects, the serum FGF21 level correlated with the VO2peak (r = -0.355, P <.001) and VFA (r= 0.487, P <.001). Stepwise multiple regression analysis showed VFA to be most strongly associated with the serum FGF21 level (β =.360, P <.001), and VO2peak was also an independent predictor of the serum FGF21 level (β = -.174, P =.019). Furthermore, the proportion of subjects with an FGF21 level below the limit of detection was significantly higher among the endurance-trained than among the untrained young men (71.4% vs24.0%, P=.001), and the VO2peak and VFA were independently associated with an undetectable FGF21 level (P <.05).Conclusions: CRF and VFA are key determinants of the circulating FGF21 concentration. Copyright © 2014 by the Endocrine Society. Source

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