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1 Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, Ohio, United States
2 Toledo, Ohio, United States; Biochemistry and Cancer Biology, Medical University of Ohio, Toledo, Ohio, United States
* To whom correspondence should be addressed. E-mail: csmas{at}meduohio.edu.
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 co-morbidities 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 2-fold 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 to wild type mice, Slc37a2 transcript is increased ~9-fold 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 post-translationally modified by addition of N-linked glycans. Slc37a2 protein migrates as heterogeneous species of ~50-75 kDa and its ectopic expression in mammalian cells results 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.
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