than MVECs from SAT. This observation could be impor- tant for explaining the deleterious effects of visceral adipose tissue. In this study, we interrogated the secretome of whole adipose tissue and subsequently cells of the stromovascu- lar fraction, preadipocytes and MVECs, to determine which component of adipose tissue was principally re- sponsible for adipokine secretion. A total of 115 proteins were identiﬁed from these three samples, of which 67 were unique to adipose tissue explants, 16 were unique to MVECs, and 7 were unique to preadipocytes. Eight pro- teins were identiﬁed in all samples, including members of the collagen family, osteonectin, metalloproteinase inhib- itor 1, C1 esterase inhibitor, plasminogen activator inhib- itor-1, and cathepsin B. These data suggest adipocytes themselves or other cells in the stromovascular fraction not interrogated in this study, including macrophages and neurons, are the key secretory cells within adipose tissue. When the secretome of whole adipose tissue was com- pared with the secretomes of both differentiated 3T3-L1 adipocytes and primary rat adipocytes, only 26 (29%) and 20 (22%) common proteins, respectively, were identiﬁed. These data infer that adipocytes alone are not the principal source of secreted proteins in adipose tissue. As the adipose tissue came from lean animals, the expected number of macrophages should be low and in fact only three secreted proteins common to the secretomes of whole adipose tissue and human macrophages were found. This leads to the important conclusion that the secretome of whole adipose tissue is not simply the sum of each of its component parts but is the result of a paracrine interaction between the multiple cell types within adipose tissue. ACKNOWLEDGMENTS This work was supported by grants from the National Health and Medical Research Council of Australia and Australian Postgraduate Awards. No potential conﬂicts of interest relevant to this article were reported. L.W. designed experiments, researched data (mass spec- trometry), analyzed data, and wrote the manuscript. S.H. designed experiments, researched data (isolation of fat pads, preadipocytes, endothelial cells), analyzed data, and wrote the manuscript. M.G. provided guidance for mass spectrometry experiments and was sadly deceased prior to project completion. D.J.C. reviewed/edited the manu- script. D.E.J. provided intellectual guidance, contributed to experimental design and discussion, and reviewed/ edited the manuscript. We thank Dr. Jerry Greenﬁeld, the Garvan Institute of Medical Research and St Vincents’ Hospital, and Dr. Shane Gray, the Garvan Institute of Medical Research, for review- ing the manuscript and the Biological Testing Facility, the Garvan Institute of Medical Research, for help with animal care. REFERENCES 1. Carey DG, Jenkins AB, Campbell LV, Freund J, Chisholm DJ. 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