TITLE:
Fatigue Alleviation Mechanism of Citric Acid Determined by Gene Expression Analysis in the Mouse Liver
AUTHORS:
Yurie Hara, Nakamichi Watanabe
KEYWORDS:
Citric Acid, Fatigue, Gluconeogenesis, Inflammation, Fatigue-Alleviation Mechanism
JOURNAL NAME:
Food and Nutrition Sciences,
Vol.6 No.12,
September
7,
2015
ABSTRACT: Citric acid has been recognized for its ability to alleviate fatigue; however, the mechanism contributing to this effect has not yet been elucidated. Our previous study suggested that the alleviation of fatigue by citric acid intake might be induced by the acceleration of gluconeogenesis. In this study, we tested this hypothesis and evaluated whether the intake of citric acid accelerates gluconeogenesis in the mouse liver through microarray analysis. Because the microarray of focus includes 200 metabolic genes, it could be used to provide information on genes related to glucose metabolism as well as other pathways such as inflammation. Eight-week-old male C57/BL6J mice were divided into the distilled water and citric acid groups (n = 6), and were administered distilled water or a citric acid solution (20 mg/30g body weight) intragastrically with a probe, respectively. Forty minutes after administration, the mice were sacrificed by decapitation. The blood glucose level of the citric acid group was significantly higher (P = 0.001) than that of the distilled water group. The expression levels of genes related to glucose metabolism (Gck, Pfkl, Pklr, Pck1, G6pc) were not changed by the intake of citric acid. On the other hand, some transcriptional differences were observed in several other genes, including those related to inflammation, blood pressure, the electron transport system, uncoupling proteins, and anti-oxidation. The expression levels of genes related to inflammation were reduced in the citric acid group; e.g., the Il6 expression level was 0.78 times lower in the citric acid group than that in the distilled water group. In conclusion, the results of this study suggest that citric acid intake could accelerate gluconeogenesis and suppresses inflammation. Therefore, the fatigue-alleviation effects of citric acid might be induced by an additive effect between the maintenance of blood glucose levels and the suppression of inflammation.