Noll Christophe, Carpentier André C
Division of Endocrinology, Department of Medicine, Centre de recherche du CHUS, Université de Sherbrooke, Sherbrooke, Quebec, Canada.
Curr Opin Lipidol. 2017 Feb;28(1):1-10. doi: 10.1097/MOL.0000000000000369.
Experimental evidences are strong for a role of long-chain saturated fatty acids in the development of insulin resistance and type 2 diabetes. Ectopic accretion of triglycerides in lean organs is a characteristic of prediabetes and type 2 diabetes and has been linked to end-organ complications. The contribution of disordered dietary fatty acid (DFA) metabolism to lean organ overexposure and lipotoxicity is still unclear, however. DFA metabolism is very complex and very difficult to study in vivo in humans.
We have recently developed a novel imaging method using PET with oral administration of 14-R,S-F-fluoro-6-thia-heptadecanoic acid (FTHA) to quantify organ-specific DFA partitioning. Our studies thus far confirmed impaired storage of DFA per volume of fat mass in abdominal adipose tissues of individuals with prediabetes. They also highlighted the increased channeling of DFA toward the heart, associated with subclinical reduction in cardiac systolic and diastolic function in individuals with prediabetes.
In the present review, we summarize previous work on DFA metabolism in healthy and prediabetic states and discuss these in the light of our novel findings using PET imaging of DFA metabolism. We herein provide an integrated view of abnormal organ-specific DFA partitioning in prediabetes in humans.
有充分的实验证据表明长链饱和脂肪酸在胰岛素抵抗和2型糖尿病的发生发展中起作用。瘦组织器官中甘油三酯的异位蓄积是糖尿病前期和2型糖尿病的一个特征,并与终末器官并发症相关。然而,饮食中脂肪酸(DFA)代谢紊乱对瘦组织器官过度暴露和脂毒性的影响仍不清楚。DFA代谢非常复杂,在人体中进行体内研究非常困难。
我们最近开发了一种新型成像方法,通过口服14-R,S-F-氟-6-硫代十七烷酸(FTHA)进行正电子发射断层扫描(PET),以量化器官特异性DFA分配。我们目前的研究证实,糖尿病前期个体腹部脂肪组织中每单位体积脂肪量的DFA储存受损。这些研究还强调,糖尿病前期个体中DFA向心脏的分流增加,这与心脏收缩和舒张功能的亚临床降低有关。
在本综述中,我们总结了之前关于健康和糖尿病前期状态下DFA代谢的研究工作,并根据我们使用DFA代谢PET成像的新发现进行讨论。我们在此提供了人类糖尿病前期异常器官特异性DFA分配的综合观点。