United States Department of Agriculture Agricultural Research Service (USDA/ARS) Children's Nutrition Research Center, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
Division of Pediatric Endocrinology and Diabetes, Texas Children's Hospital, Baylor College of Medicine, Houston, Texas, USA.
JCI Insight. 2021 Feb 22;6(4):146000. doi: 10.1172/jci.insight.146000.
BACKGROUNDMetabolic flexibility (MF) refers to the relative ability to utilize lipid and carbohydrate substrates and to transition between them. It is not clear whether MF is impaired in obese youth and what the determining factors are.METHODSWe investigated the determinants of MF (increased respiratory exchange ratio [ΔRER] under insulin-stimulated conditions) in pubertal youth (n = 104; 15.6 ± 1.8 years) with obesity across the spectrum of glucose tolerance compared with normal weight (NW) controls, including body composition (fat-free mass [FFM], %body fat), visceral adipose fat (VAT) (MRI), glycemia, and insulin sensitivity (IS) [3-hour hyperinsulinemic-euglycemic clamp with measurement of lipolysis ([2H5] glycerol), free fatty acids (FFAs), and RER (indirect calorimetry)].RESULTSYouth with prediabetes and type 2 diabetes had lower ΔRER and oxidative and nonoxidative glucose disposal compared with NW, with no significant difference in ΔRER between NW and obese with normal glucose tolerance. In multiple regression analysis, ISFFM (β = 0.4, P = 0.004), percentage suppression of FFAs (r = 0.26, P = 0.007), and race/ethnicity (β = -0.23, P = 0.02) contributed to the variance in ΔRER (R2 = 0.30, P < 0.001) independent of percentage body fat (or VAT), sex, Tanner stage, and hemoglobin A1c.ConclusionMF is defective at the extreme of the metabolic phenotype in obese youth with dysglycemia related to a defect in IS limiting substrate utilization.FUNDINGUSDA/ARS Project Number 3092-51000-057.
代谢灵活性（MF）是指利用脂质和碳水化合物底物并在它们之间转换的相对能力。目前尚不清楚肥胖青少年的 MF 是否受损，以及其决定因素是什么。
我们研究了代谢灵活性（胰岛素刺激下呼吸交换率增加[ΔRER]）的决定因素，参与者为青春期肥胖青少年（n=104；15.6±1.8 岁），涵盖了葡萄糖耐量谱，与正常体重（NW）对照组相比，包括身体成分（去脂体重[FFM]，%体脂肪）、内脏脂肪（VAT）（MRI）、血糖和胰岛素敏感性（IS）[3 小时高胰岛素正葡萄糖钳夹，测量脂肪分解（[2H5]甘油）、游离脂肪酸（FFA）和 RER（间接测热法）]。
与 NW 相比，患有糖尿病前期和 2 型糖尿病的青少年的 ΔRER 和氧化及非氧化葡萄糖处置能力较低，NW 与葡萄糖耐量正常的肥胖青少年之间的 ΔRER 无显著差异。在多元回归分析中，ISFFM（β=0.4，P=0.004）、FFA 抑制百分比（r=0.26，P=0.007）和种族/民族（β=-0.23，P=0.02）与 ΔRER 的方差相关（R2=0.30，P<0.001），独立于体脂肪（或 VAT）百分比、性别、Tanner 分期和糖化血红蛋白。
在患有糖代谢异常的肥胖青少年中，代谢灵活性在代谢表型的极端状态下受损，与 IS 限制底物利用的缺陷有关。
美国农业部/ARS 项目编号 3092-51000-057。
