Adiponectin, chemerin, cytokines, and dipeptidyl peptidase 4 are released from human adipose tissue in a depot-dependent manner: an in vitro system including human serum albumin

BACKGROUND Adipose tissue (AT) contributes to metabolic dysfunction through imbalanced production of adipokines, including cytokines. Visceral AT in particular is associated with metabolic disorders, indicating a specific secretory status. The relative significance of different human AT depots in adipokine release is not fully known. Further, previous in vitro systems usually included medium containing bovine serum albumin (BSA), which may induce cytokine release. Our aim was to compare release of a number of adipokines/cytokines - all implicated in insulin resistance - from human subcutaneous and visceral AT in a short-term incubation system minimizing cytokine induction and including repeated measurements during 24 h. A prerequisite was to evaluate a potential alternative to BSA in the incubation medium. METHODS Subcutaneous and/or visceral AT from 17 patients (age 20-68 years; BMI 22.6-56.7 kg/m2) undergoing elective surgery was incubated for 2, 4, 6, 8, and 24 h in medium with or without 1% BSA or human serum albumin (HSA). Medium concentrations of adiponectin, chemerin, nine cytokines, dipeptidyl peptidase 4 (DPP4), and omentin were analyzed by multiplex immunoassay or ELISA. Adipocyte size, AT macrophage density, and medium concentrations of endotoxin were determined. RESULTS Cytokine release was induced by BSA but not by HSA. In evaluation of the final incubation protocol including 1% HSA, and as expected, adiponectin release was higher from subcutaneous biopsies of nonobese than of obese subjects and inversely associated with adipocyte size; omentin was released almost exclusively from visceral AT. Exploratory incubations revealed more abundant release of chemerin, cytokines (except IL-6), and DPP4 from the visceral depot, while adiponectin release was higher from subcutaneous than visceral AT. Release was linear for a maximum of 2-6 h. Macrophage density was higher in visceral than subcutaneous AT. Levels of endotoxin in the medium were negligible. CONCLUSIONS Adiponectin, chemerin, many cytokines, and DPP4 are released from human AT in a depot-dependent manner. These results highlight functional differences between visceral and subcutaneous AT, and a mechanistic link between regional fat accumulation and metabolic disorders. Supplementation of human AT incubation medium with HSA rather than BSA is recommended to minimize induction of cytokine release.