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Lactate dehydrogenase in adipocyte regulates glucose metabolism

峰村, 友美 大阪大学 DOI:10.18910/88169

2022.03.24

概要

Plasma glucose concentrations are homeostatically regulated and maintained within strict boundaries. During fasting, liver produces glucose via gluconeogenesis stimulated by hormonal factors, however, little has been known about the mechanism of adipose tissue to regulate glucose uptake during fasting.

Here, I revealed that expression levels of 8 glycolytic enzymes were significantly reduced in adipose tissue under fasting conditions using public microarray database. Among them, I focused on lactate dehydrogenase A, which is responsible for conversion of pyruvate into lactate, the last step of glycolysis pathway. In adipose tissues of WT mice, LDHA expression decreased in parallel with reduced Glut1 protein, a major glucose transporter during fasting. To elucidate the significance of LDHA in adipocytes, I generated adipocyte-specific LDHA knockout mice (AdLDHAKO). AdLDHAKO mice showed no apparent differences in body weight and tissue weight. Under fasting conditions, ADLDHAKO mice exhibited significantly decreased Glut1 protein. Subsequently, adipose tissue of AdLDHAKO mice exhibited reduced glucose uptake than that of control mice.

These results indicate that LDHA-deficiency causes reduction of Glut1 protein and glucose uptake, suggesting that there is a new mechanism to reduce glucose uptake. Considering that both LDHA and Glut1 expressions are decreased during fasting, LDHA might regulate glucose uptake in adipose tissues to supply it to other demanding organs. It could lead to a new insight of adipose tissue as a metabolic organ to maintain glucose homeostasis by reducing glucose uptake during fasting, in addition to taking up excess glucose during feeding.

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