Exercise Physiology Laboratory, Department of Integrative Biology, University of California, Berkeley, California, United States.
Division of Endocrinology, Department of Medicine, University of California, San Francisco, California, United States.
J Appl Physiol (1985). 2024 Nov 1;137(5):1200-1219. doi: 10.1152/japplphysiol.00437.2024. Epub 2024 Sep 5.
Plasma glycerol and free fatty acid concentrations decrease following oral glucose consumption, but changes in the rate of lipolysis during an oral glucose tolerance test (OGTT) have not been documented in conjunction with changes in fatty acid (FA) oxidation or reesterification rates in healthy individuals. After a 12-h overnight fast, 15 young (21-35 yr; 7 men and 8 women) and 14 older (60-80 yr; 7 men and 7 women) participants had the forearm vein catheterized for primed continuous infusion of [1,1,2,3,3-H]glycerol. A contralateral hand vein was catheterized for arterialized blood sampling. Indirect calorimetry was performed simultaneously to determine total FA and carbohydrate (CHO) oxidation rates (Rox). Total FA reesterification rates (Rs) were estimated from tracer-measured lipolytic and FA oxidation rates. After a 90-min equilibration period, participants underwent a 120-min, 75-g OGTT. Glycerol rate of appearance (Ra), an index of lipolysis, decreased significantly from baseline 5 min postchallenge in young participants and 30 min in older participants. At 60 min, FA Rox decreased in both groups, but was significantly higher in older participants. Between 5 and 90 min, CHO Rox was significantly lower in older participants. In addition, FA Rs was significantly lower in older participants at 60 and 90 min. The area under the curve (AUC) for FA Rox was greater than that for FA Rs in older, but not in young participants. Our results indicate that, in aging, the postprandial suppression of lipolysis and FA oxidation are delayed such that FA oxidation is favored over CHO oxidation and FA reesterification. To our knowledge, our investigation is the first to demonstrate changes in lipolysis during an oral glucose tolerance test (OGTT) in healthy young and older individuals. Plasma glycerol and free fatty acid concentrations changed after glycerol rate of appearance (Ra), indicating that plasma concentrations are incomplete surrogates of the lipolytic rate. Moreover, simultaneous determinations of substrate oxidation rates are interpreted to indicate that metabolic inflexibility in aging is characterized by delayed changes in postprandial substrate utilization related to the lipolytic rate.
血浆甘油和游离脂肪酸浓度在口服葡萄糖后降低，但健康个体在口服葡萄糖耐量试验（OGTT）期间的脂肪分解率变化与脂肪酸（FA）氧化或再酯化率的变化尚未有相关记录。在 12 小时的夜间禁食后，15 名年轻（21-35 岁；7 名男性和 8 名女性）和 14 名年长（60-80 岁；7 名男性和 7 名女性）参与者在前臂静脉内置入用于持续输注[1,1,2,3,3-H]甘油的套管。对侧手部静脉内置入用于动脉化采血。同时进行间接测热法以确定总 FA 和碳水化合物（CHO）氧化率（Rox）。总 FA 再酯化率（Rs）通过示踪剂测量的脂肪分解和 FA 氧化率来估计。在 90 分钟的平衡期后，参与者进行 120 分钟、75 克 OGTT。年轻参与者在挑战后 5 分钟和年长参与者在 30 分钟时，甘油出现率（Ra），即脂肪分解的指标，显著低于基线。在 60 分钟时，两组的 FA Rox 均下降，但年长参与者的下降幅度显著更高。在 5 至 90 分钟之间，年长参与者的 CHO Rox 显著降低。此外，在 60 和 90 分钟时，年长参与者的 FA Rs 显著降低。在年长参与者中，FA Rox 的 AUC 大于 FA Rs，而在年轻参与者中则不然。我们的结果表明，在衰老过程中，餐后脂肪分解和 FA 氧化的抑制被延迟，从而使 FA 氧化优先于 CHO 氧化和 FA 再酯化。据我们所知，我们的研究首次证明了健康年轻和年长个体在口服葡萄糖耐量试验（OGTT）期间脂肪分解的变化。甘油出现率（Ra）后血浆甘油和游离脂肪酸浓度发生变化，表明血浆浓度不能完全替代脂肪分解率。此外，对底物氧化率的同时测定表明，衰老时代谢灵活性的特征是与脂肪分解率相关的餐后底物利用变化延迟。
