Montastier Émilie, Ye Run Zhou, Noll Christophe, Amrani Mehdi, Frisch Frédérique, Fortin Mélanie, Bouffard Lucie, Phoenix Serge, Sarrhini Otman, Cunnane Stephen C, Guérin Brigitte, Turcotte Eric E, Carpentier André C
Division of Endocrinology, Department of Medicine, Centre de Recherche du CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Department of Nuclear Medicine and Radiobiology, Centre de Recherche du CHUS, Université de Sherbrooke, Quebec, Canada.
Eur J Pharmacol. 2025 Jul 5;998:177563. doi: 10.1016/j.ejphar.2025.177563. Epub 2025 Mar 27.
Increased adipose tissue (AT) dietary fatty acids (DFA) trapping limits fatty acid exposure to lean organs in the face of elevated postprandial nonesterified fatty acid (NEFA) flux from excess AT intracellular lipolysis in prediabetes. We hypothesized that pharmacological inhibition of postprandial AT intracellular lipolysis using short-acting nicotinic acid (NA) would increase AT DFA trapping and limit AT NEFA spillover to lean organs in subjects with prediabetes. Twenty subjects with impaired glucose tolerance and 19 individuals with normal glucose tolerance underwent four postprandial studies with positron emission tomography/computed tomography with radio-labeled fatty acid tracers and stable isotopic palmitate tracers. Over the 6-h postprandial period, NA increased AT DFA partitioning with reciprocal reduction in liver and in muscle. NA also robustly reduced cardiac and liver total (DFA + NEFA) postprandial fatty acid uptake. Short-acting NA administered postprandially thus enhances AT DFA trapping and markedly reduces postprandial hepatic and cardiac fatty acid uptake. (clinicaltrials.gov NCT02808182).
在糖尿病前期,过量脂肪组织(AT)细胞内脂解导致餐后非酯化脂肪酸(NEFA)通量升高,此时增加的AT膳食脂肪酸(DFA)捕获可限制脂肪酸暴露于瘦组织器官。我们假设,使用短效烟酸(NA)对餐后AT细胞内脂解进行药理学抑制,会增加AT对DFA的捕获,并限制糖尿病前期受试者的AT中NEFA向瘦组织器官的溢出。20名糖耐量受损受试者和19名糖耐量正常个体接受了四项餐后研究,使用放射性标记脂肪酸示踪剂和稳定同位素棕榈酸示踪剂进行正电子发射断层扫描/计算机断层扫描。在餐后6小时期间,NA增加了AT对DFA的分配,同时肝脏和肌肉中的分配相应减少。NA还显著降低了心脏和肝脏餐后总(DFA+NEFA)脂肪酸摄取。因此,餐后给予短效NA可增强AT对DFA的捕获,并显著降低餐后肝脏和心脏的脂肪酸摄取。(临床试验.gov NCT02808182)