CONTEXT Studies on human renal metabolism are scanty. Nowadays, functional imaging allows the characterization of renal metabolism in a non-invasive manner. We have recently demonstrated that [18F]FDG-PET can be used to analyze renal glucose uptake rates (GU), and that the renal cortex is an insulin sensitive tissue. OBJECTIVE To confirm that renal GU is decreased in people with obesity, and to test whether circulating metabolites are related to renal GU. DESIGN, SETTING AND PARTICIPANTS 18 people with obesity and 18 non-obese controls were studied with [18F]FDG-PET during insulin clamp. Renal scans were obtained ∼60 min after [18F]FDG injection. Renal GU was measured using fractional uptake rate and after correcting for residual intratubular [18F]FDG. Circulating metabolites were measured using high-throughput proton NMR metabolomics. RESULTS Cortical GU was higher in healthy non-obese controls compared to people with obesity (4.7 [3.4-5.6] vs 3.1 [2.2-4.3], p = 0.004, respectively), and it associated positively with the degree of insulin sensitivity (M value) (r = 0.42, p = 0.01). Moreover, cortical GU was inversely associated with circulating β-OH-butyrate (r = -0.58, p = 0.009), acetoacetate (r = -0.48, p = 0.008), citrate (r = -0.44, p = 0.01) and free fatty acids (FFA) (r = -0.68, p < 0.0001), even when accounting for the M value. On the contrary, medullary GU was not associated with any clinical parameters. CONCLUSIONS These data confirm differences in renal cortical GU between people with obesity and healthy non-obese controls. Moreover, the negative correlations between renal cortex GU and FFA, ketone bodies and citrate are suggestive of substrate competition in the renal cortex.

中文翻译：

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胰岛素抵抗时肾皮质葡萄糖摄取减少，并与血清游离脂肪酸成反比。

背景 对人类肾脏代谢的研究很少。如今，功能成像可以以非侵入性方式表征肾脏代谢。我们最近证明[18F]FDG-PET可用于分析肾葡萄糖摄取率（GU），并且肾皮质是胰岛素敏感组织。目的 证实肥胖人群肾 GU 降低，并检测循环代谢物是否与肾 GU 相关。设计、设置和参与者 在胰岛素钳夹期间使用 [18F]FDG-PET 对 18 名肥胖者和 18 名非肥胖对照者进行了研究。[18F]FDG 注射后约 60 分钟进行肾脏扫描。使用分数摄取率并在校正残余管内[18F]FDG后测量肾GU。使用高通量质子核磁共振代谢组学测量循环代谢物。结果 与肥胖者相比，健康非肥胖对照者的皮质 GU 较高（分别为 4.7 [3.4-5.6] vs 3.1 [2.2-4.3]，p = 0.004），并且与胰岛素敏感性程度呈正相关（M值）（r = 0.42，p = 0.01）。此外，皮质 GU 与循环 β-OH-丁酸 (r = -0.58，p = 0.009)、乙酰乙酸 (r = -0.48，p = 0.008)、柠檬酸 (r = -0.44，p = 0.01) 和游离酸呈负相关。脂肪酸 (FFA)（r = -0.68，p < 0.0001），即使考虑了 M 值。相反，髓质 GU 与任何临床参数均无关。结论 这些数据证实了肥胖者和健康非肥胖者之间肾皮质 GU 的差异。此外，肾皮质GU与FFA、酮体和柠檬酸盐之间的负相关性表明肾皮质中存在底物竞争。