Effects of exogenous lactate on lipid, protein, and glucose metabolism-a randomized crossover trial in healthy males.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM American journal of physiology. Endocrinology and metabolism Pub Date : 2024-04-01 Epub Date: 2024-02-07 DOI:10.1152/ajpendo.00301.2023
Mette G B Pedersen, Nikolaj Rittig, Maj Bangshaab, Kristoffer Berg-Hansen, Nigopan Gopalasingam, Lars C Gormsen, Esben Søndergaard, Niels Møller
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Abstract

Lactate may inhibit lipolysis and thus enhance insulin sensitivity, but there is a lack of metabolic human studies. This study aimed to determine how hyperlactatemia affects lipolysis, glucose- and protein metabolism, and insulin sensitivity in healthy men. In a single-blind, randomized, crossover design, eight healthy men were studied after an overnight fast on two occasions: 1) during a sodium-lactate infusion (LAC) and 2) during a sodium-matched NaCl infusion (CTR). Both days consisted of a 3-h postabsorptive period followed by a 3-h hyperinsulinemic-euglycemic clamp (HEC). Lipolysis rate, endogenous glucose production (EGP), and delta glucose rate of disappearance (ΔRdglu) were evaluated using [9,10-3H]palmitate and [3-3H]glucose tracers. In addition, whole body- and forearm protein metabolism was assessed using [15N]phenylalanine, [2H4]tyrosine, [15N]tyrosine, and [13C]urea tracers. In the postabsorptive period, plasma lactate increased to 2.7 ± 0.5 mmol/L during LAC vs. 0.6 ± 0.3 mmol/L during CTR (P < 0.001). In the postabsorptive period, palmitate flux was 30% lower during LAC compared with CTR (84 ± 32 µmol/min vs. 120 ± 35 µmol/min, P = 0.003). During the HEC, palmitate flux was suppressed similarly during both interventions (P = 0.7). EGP, ΔRdglu, and M value were similar during LAC and CTR. During HEC, LAC increased whole body phenylalanine flux (P = 0.02) and protein synthesis (P = 0.03) compared with CTR; LAC did not affect forearm protein metabolism compared with CTR. Lactate infusion inhibited lipolysis by 30% under postabsorptive conditions but did not affect glucose metabolism or improve insulin sensitivity. In addition, whole body phenylalanine flux was increased. Clinical trial registrations: NCT04710875.NEW & NOTEWORTHY Lactate is a decisive intermediary metabolite, serving as an energy substrate and a signaling molecule. The present study examines the effects of lactate on substrate metabolism and insulin sensitivity in healthy males. Hyperlactatemia reduces lipolysis by 30% without affecting insulin sensitivity and glucose metabolism. In addition, hyperlactatemia increases whole body amino acid turnover rate.

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外源性乳酸盐对脂质、蛋白质和葡萄糖代谢的影响--一项针对健康男性的随机交叉试验。
背景:乳酸可抑制脂肪分解,从而增强胰岛素敏感性,但目前还缺乏对人体代谢的研究。本研究旨在确定高乳酸血症如何影响健康男性的脂肪分解、葡萄糖和蛋白质代谢以及胰岛素敏感性。研究方法采用单盲、随机、交叉设计的方法,对 8 名健康男性在一夜禁食后进行了两次研究:1)钠-乳酸盐输注(LAC)期间;2)钠匹配氯化钠输注(CTR)期间。这两天都包括 3 小时的吸收后时间,然后是 3 小时的高胰岛素血糖钳夹(HEC)。使用[9,10-3H]棕榈酸酯和[3-3H]葡萄糖示踪剂评估了脂肪分解率、内源性葡萄糖生成(EGP)和δ葡萄糖消失率(ΔRdglu)。此外,还使用[15N]苯丙氨酸、[2H4]酪氨酸、[15N]酪氨酸和[13C]尿素示踪剂评估了全身和前臂的蛋白质代谢。结果:在吸收后阶段,LAC期间血浆乳酸增至2.7±0.5 mmol/L,而CTR期间为0.6±0.3 mmol/L(pglu和M值在LAC和CTR期间相似)。在 HEC 期间,与 CTR 相比,LAC 增加了全身苯丙氨酸通量(p=0.02)和蛋白质合成(p=0.03);与 CTR 相比,LAC 不影响前臂蛋白质代谢。结论在吸收后条件下,输注乳酸可抑制脂肪分解 30%,但不会影响糖代谢或改善胰岛素敏感性。此外,全身苯丙氨酸通量增加。临床试验注册:NCT04710875。
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来源期刊
CiteScore
9.80
自引率
0.00%
发文量
98
审稿时长
1 months
期刊介绍: The American Journal of Physiology-Endocrinology and Metabolism publishes original, mechanistic studies on the physiology of endocrine and metabolic systems. Physiological, cellular, and molecular studies in whole animals or humans will be considered. Specific themes include, but are not limited to, mechanisms of hormone and growth factor action; hormonal and nutritional regulation of metabolism, inflammation, microbiome and energy balance; integrative organ cross talk; paracrine and autocrine control of endocrine cells; function and activation of hormone receptors; endocrine or metabolic control of channels, transporters, and membrane function; temporal analysis of hormone secretion and metabolism; and mathematical/kinetic modeling of metabolism. Novel molecular, immunological, or biophysical studies of hormone action are also welcome.
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