Janus-faced citrate in aging and metabolism

Citrate, one of the tricarboxylic acid cycle inter-mediates, plays an important role in cellular energy metabolism. Citrate is also a common food ingredient, occurring in numerous juices and beverages, and potassium citrate has been used to treat kidney stones in some patients. However, the long-term effects of exogenous citrate administration on overall health has not been well explored. In a recent study, we demonstrated that dietary citrate supplementation was associated with lifespan extension, decreased hemolymph glucose and triglyceride, and reduced ATP/ADP ratio in fruit flies fed on a relatively high-calorie diet [1]. Furthermore, we found that AMP-activated protein kinase (AMPK) was activated and target of rapamycin (TOR) signaling was suppressed in these flies. In line with the aforementioned findings, parallel experiments in mice fed a high-fat diet showed similar metabolic benefits for citrate supplementation, including improved glucose homeostasis and reduced hepatic lipid accumulation. These mice also exhibited better social memory and novel object recognition memory in a citrate dose-dependent manner.