Michio Otsuki
   Department   School of Medicine(Tokyo Women's Medical University Hospital), School of Medicine
   Position   Professor and Division head
Article types Original article
Language English
Peer review Peer reviewed
Title Lactate dehydrogenase regulates basal glucose uptake in adipocytes.
Journal Formal name:Biochemical and biophysical research communications
Abbreviation:Biochem Biophys Res Commun
ISSN code:10902104/0006291X
Domestic / ForeginForegin
Volume, Issue, Page 607,pp.20-27
Author and coauthor Minemura Tomomi, Fukuhara Atsunori, Otsuki Michio, Shimomura Iichiro
Publication date 2022/06
Summary Plasma glucose levels are homeostatically regulated within strict boundaries and are maintained through a balance between peripheral glucose uptake and hepatic glucose production. However, little is known about the regulatory mechanism of glucose uptake in adipocytes during fasting. Under fasting conditions, the expression levels of 8 glycolytic enzymes were significantly reduced in adipose tissue. Among them, we focused on lactate dehydrogenase A (LDHA), the last enzyme of the glycolytic pathway. Under fasting conditions, both LDHA and Glut1 protein levels tended to decrease in adipose tissue. To elucidate the significance of LDHA in adipocytes, we generated adipocyte-specific LDHA knockout mice (AdLDHAKO) for the first time. AdLDHAKO mice showed no apparent changes in body weight or tissue weight. Under fasting conditions, AdLDHAKO mice exhibited a significant reduction in Glut1 protein levels and glucose uptake in adipose tissues compared with control mice. Similarly, siRNA of LDHA in 3T3-L1 adipocytes reduced Glut1 protein levels and basal glucose uptake. Moreover, treatment with bafilomycin A1, an inhibitor of lysosomal protein degradation, restored Glut1 protein levels by siRNA of LDHA. These results indicate that LDHA regulates Glut1 expression and basal glucose uptake in adipocytes.
DOI 10.1016/j.bbrc.2022.03.113
PMID 35366539