The major facilitator superfamily member Slc37a2 is a novel macrophage- specific gene selectively expressed in obese white adipose tissue.
A marked degree of macrophage infiltration of white adipose tissue (WAT) occurs in obesity and may link excess adiposity with the chronic inflammatory state underlying metabolic syndrome and other comorbidities of obesity. Excess deposition of fat in the intra-abdominal vs. subcutaneous WAT depots is a key component of metabolic syndrome. Through construction and differential screening of a murine ob/ob WAT cDNA library, we identified Slc37a2, a novel sugar transporter of the major facilitator superfamily, to be twofold enriched in intra-abdominal vs. subcutaneous fat. We find Slc37a2 is a macrophage-enriched transcript. In murine tissues, Slc37a2 transcript is restricted to spleen, thymus, and obese WAT. It is also readily detected in the RAW264.7 macrophage cell line and increases 46-fold during macrophage differentiation of THP-1 human monocytes. Compared with wild-type mice, Slc37a2 transcript is increased epididymal ninefold in ob/ob WAT and assessment of expression of the macrophage marker emr1 indicated upregulation of Slc37a2 transcript in macrophages populating ob/ob WAT. Studies with PNGase F and tunicamycin reveal the Slc37a2 protein is posttranslationally modified by addition of N-linked glycans. Slc37a2 protein migrates as heterogeneous species of approximately 50-75 kDa and its ectopic expression in mammalian cells results in the appearance of large intracellular vacuoles. We postulate that the function of this macrophage-specific putative sugar transporter is central to the metabolism of the macrophage population specifically present in obese WAT.
Kim
Ji Young
JY
Department of Biochemistry and Cancer Biology, Medical University of Ohio, 3000 Arlington Ave., Toledo, OH 43614, USA.
Tillison
Kristin
K
Zhou
Shengli
S
Wu
Yu
Y
Smas
Cynthia M
CM
D052436:Adipose Tissue, White / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D017920:Antiporters / Q000235:genetics* / Q000378:metabolism*; D019556:COS Cells; D002634:Chemotaxis, Leukocyte; D002522:Chlorocebus aethiops; D006367:HeLa Cells; D006801:Humans; D050152:Intra-Abdominal Fat / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics* / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D008820:Mice, Obese; D008969:Molecular Sequence Data; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D009928:Organ Specificity; D014162:Transfection
D017920:Antiporters; D026901:Membrane Transport Proteins; C569995:Slc37a2 protein, human; C522574:Slc37a2 protein, mouse