Anti-EMR1 monoclonal antibody, clone Cl:A3-1 [APC]

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 wildtype 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 similar to 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 macrophagespecific putative sugar transporter is central to the metabolism of the macrophage population specifically present in obese WAT.

Background: Visceral white adipose tissue (WAT) hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. Results: C57BL/6 J mice were fed a high-fat diet (HFD) or normal diet (ND) and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery) after 2-4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9) and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14). Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. Conclusions: In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of diet-induced obesity.