Maltais-Payette Ina, Vijay Jinchu, Simon Marie-Michelle, Corbeil Jacques, Brière Francis, Grundberg Elin, Tchernof André
Quebec Heart and Lung Institute, Laval University, 2725 Chemin Sainte-Foy (Y-4212), Québec, Québec, Canada.
School of Nutrition, Laval University, Québec, Québec, Canada.
Amino Acids. 2022 Sep;54(9):1287-1294. doi: 10.1007/s00726-022-03181-1. Epub 2022 Jul 9.
Circulating levels of the amino acid glutamate are associated with central fat accumulation, yet the pathophysiology of this relationship remains unknown. We aimed to (i) refine and validate the association between circulating glutamate and abdominal obesity in a large twin cohort, and (ii) investigate whether transcriptomic profiles in adipose tissue could provide insight into the biological mechanisms underlying the association. First, in a cohort of 4665 individuals from the TwinsUK resource, we identified individuals with abdominal obesity and compared prevalence of the latter across circulating glutamate quintiles. Second, we used transcriptomic signatures generated from adipose tissue, both subcutaneous and visceral, to investigate associations with circulating glutamate levels. Individuals in the top circulating glutamate quintile had a sevenfold higher prevalence of abdominal obesity compared to those in the bottom quintile. The adipose tissue transcriptomic analyses identified GLUL, encoding Glutamate-Ammonia Ligase, as being associated with circulating glutamate and abdominal obesity, with pronounced signatures in the visceral depot. In conclusion, circulating glutamate is positively associated with the prevalence of abdominal obesity which relates to dysregulated GLUL expression specifically in visceral adipose tissue.
氨基酸谷氨酸的循环水平与中心性脂肪堆积有关，然而这种关系的病理生理学仍然未知。我们旨在：（i）在一个大型双胞胎队列中细化并验证循环谷氨酸与腹部肥胖之间的关联，以及（ii）研究脂肪组织中的转录组谱是否能为这种关联背后的生物学机制提供见解。首先，在来自英国双胞胎资源库的4665名个体的队列中，我们确定了腹部肥胖个体，并比较了循环谷氨酸五分位数中腹部肥胖的患病率。其次，我们使用从皮下和内脏脂肪组织生成的转录组特征，来研究与循环谷氨酸水平的关联。循环谷氨酸最高五分位数的个体与最低五分位数的个体相比，腹部肥胖的患病率高出七倍。脂肪组织转录组分析确定，编码谷氨酸-氨连接酶的GLUL与循环谷氨酸和腹部肥胖相关，在内脏脂肪库中有明显的特征。总之，循环谷氨酸与腹部肥胖的患病率呈正相关，这与内脏脂肪组织中GLUL表达失调有关。
