Large-Scale Analysis of Circulating Amino Acids and Adipose Gene Expression in Relation to Abdominal Obesity

ABSTRACT Background Circulating level of the amino acid glutamate is 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 population-based twin cohort; and ii) investigate whether transcriptomic profiles in adipose tissue could provide insight into biological mechanisms underlying the association. Methods First, in a cohort of 4,665 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. Results Individuals in the top circulating glutamate quintile had a 7-fold 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. Conclusion Circulating glutamate is positively associated with the prevalence of abdominal obesity which relates to dysregulated GLUL expression specifically in visceral adipose tissue.