Department of Human Biology, Nutrition and Toxicology Research Institute Maastricht, Maastricht University, Maastricht, The Netherlands.
Obesity (Silver Spring). 2010 Jul;18(7):1369-77. doi: 10.1038/oby.2009.377. Epub 2009 Oct 29.
Both obesity and insulin resistance have been related to low fat oxidation rates, which may be genetically determined. The association between variation in fat oxidation rates among obese subjects and genotype was studied for 42 common single-nucleotide polymorphisms (SNPs) in 26 candidate genes for fat oxidation, insulin resistance, and obesity, including FTO. Energy expenditure (EE) and fat oxidation were measured with indirect calorimetry during fasting and 3 h after a high fat load containing 95 energy% of fat (60% saturated fat, energy content 50% of estimated resting EE) in 722 obese subjects (541 women, 181 men) from 8 European centers. After adjustment for center and gender, -178 A>C CD36 (rs2232169) (P = 0.02), -22510 C>G SLC6A14 (women, rs2011162) (P = 0.03), and T690S C>G PCSK1 (rs6235) (P = 0.02) were related to a reduced fat oxidation, whereas 17 C>G SREBF1 (17 C>G) (P = 0.01) was related to increased fat oxidation in the fasting state. The ability to increase fat oxidation after a high fat load was increased in subjects with -174 G>C IL6 (rs1800795) (P = 0.01). Effect sizes range from 1.1 to 3.1% differences in fat oxidation (expressed as % of EE). FTO rs9939609 was not related to fat oxidation. At the same time, the results are not adjusted for multiple testing, thus none of the associations can be considered statistically significant. The results should therefore only be considered as leads to new hypotheses about effects of specific genetic polymorphisms on fasting and postprandial fat oxidation.
肥胖和胰岛素抵抗与低脂肪氧化率有关，而这种低脂肪氧化率可能是由基因决定的。本研究旨在探讨肥胖者脂肪氧化率的个体差异与基因型之间的关系，共检测了 26 个候选基因中的 42 个常见单核苷酸多态性（SNP），这些基因涉及脂肪氧化、胰岛素抵抗和肥胖。在 8 个欧洲中心的 722 名肥胖者（541 名女性，181 名男性）中，空腹时和高脂肪负荷后 3 小时（高脂肪负荷含有 95%的能量来自脂肪[60%为饱和脂肪，能量含量为估计静息能量消耗的 50%]）时通过间接热量法测量能量消耗（EE）和脂肪氧化。在调整中心和性别因素后，CD36（rs2232169，-178A>C）（P=0.02）、SLC6A14（rs2011162，-22510C>G，女性）（P=0.03）和 PCSK1（rs6235，T690S>C>G）与脂肪氧化减少有关，而 SREBF1（rs1800795，17C>G）（P=0.01）与空腹时脂肪氧化增加有关。高脂肪负荷后脂肪氧化增加的能力在 IL6（rs1800795，-174G>C）的受试者中增强（P=0.01）。脂肪氧化的差异效应大小范围为 1.1%至 3.1%（以 EE 的百分比表示）。FTO rs9939609 与脂肪氧化无关。同时，这些结果未经多重检验调整，因此，不能认为这些关联具有统计学意义。因此，这些结果只能被视为关于特定遗传多态性对空腹和餐后脂肪氧化影响的新假说的线索。
