Institute of Cardiovascular and Medical Sciences, University of Glasgow, Glasgow, United Kingdom.
PLoS One. 2010 Dec 1;5(12):e14197. doi: 10.1371/journal.pone.0014197.
South Asians are more insulin resistant than Europeans, which cannot be fully explained by differences in adiposity. We investigated whether differences in oxidative capacity and capacity for fatty acid utilisation in South Asians might contribute, using a range of whole-body and skeletal muscle measures.
METHODOLOGY/PRINCIPAL FINDINGS: Twenty men of South Asian ethnic origin and 20 age and BMI-matched men of white European descent underwent exercise and metabolic testing and provided a muscle biopsy to determine expression of oxidative and lipid metabolism genes and of insulin signalling proteins. In analyses adjusted for age, BMI, fat mass and physical activity, South Asians, compared to Europeans, exhibited; reduced insulin sensitivity by 26% (p = 0.010); lower VO2max (40.6±6.6 vs 52.4±5.7 ml x kg(-1) x min(-1), p = 0.001); and reduced fat oxidation during submaximal exercise at the same relative (3.77±2.02 vs 6.55±2.60 mg x kg(-1) x min(-1) at 55% VO2max, p = 0.013), and absolute (3.46±2.20 vs 6.00±1.93 mg x kg(-1) x min(-1) at 25 ml O(2) x kg(-1) x min(-1), p = 0.021), exercise intensities. South Asians exhibited significantly higher skeletal muscle gene expression of CPT1A and FASN and significantly lower skeletal muscle protein expression of PI3K and PKB Ser473 phosphorylation. Fat oxidation during submaximal exercise and VO2max both correlated significantly with insulin sensitivity index and PKB Ser473 phosphorylation, with VO2max or fat oxidation during exercise explaining 10-13% of the variance in insulin sensitivity index, independent of age, body composition and physical activity.
CONCLUSIONS/SIGNIFICANCE: These data indicate that reduced oxidative capacity and capacity for fatty acid utilisation at the whole body level are key features of the insulin resistant phenotype observed in South Asians, but that this is not the consequence of reduced skeletal muscle expression of oxidative and lipid metabolism genes.
南亚人比欧洲人胰岛素抵抗更严重，而这种差异不能完全用体脂差异来解释。我们通过一系列全身和骨骼肌测量来研究南亚人氧化能力和脂肪酸利用能力的差异是否会导致这种情况。
方法/主要发现：20 名南亚裔男性和 20 名年龄和 BMI 匹配的欧洲白种人男性接受了运动和代谢测试，并提供了肌肉活检，以确定氧化和脂质代谢基因以及胰岛素信号蛋白的表达。在调整年龄、BMI、脂肪量和体力活动的分析中，与欧洲人相比，南亚人表现出：胰岛素敏感性降低 26%（p=0.010）；最大摄氧量（VO2max）降低 40.6±6.6 比 52.4±5.7 ml x kg(-1) x min(-1)，p=0.001）；以及在相同相对（55%VO2max 时为 3.77±2.02 比 6.55±2.60 mg x kg(-1) x min(-1)，p=0.013）和绝对（25 ml O(2) x kg(-1) x min(-1) 时为 3.46±2.20 比 6.00±1.93 mg x kg(-1) x min(-1)，p=0.021）运动强度下的亚最大运动时脂肪氧化减少。南亚人骨骼肌中 CPT1A 和 FASN 的基因表达明显更高，PI3K 和 PKB Ser473 磷酸化的骨骼肌蛋白表达明显更低。亚最大运动时的脂肪氧化和 VO2max 与胰岛素敏感性指数和 PKB Ser473 磷酸化均呈显著相关，VO2max 或运动时的脂肪氧化可以解释胰岛素敏感性指数 10-13%的变化，与年龄、身体成分和体力活动无关。
结论/意义：这些数据表明，全身氧化能力和脂肪酸利用能力的降低是南亚人胰岛素抵抗表型的关键特征，但这不是骨骼肌氧化和脂质代谢基因表达减少的结果。
