Adipose tissue is a dynamic secretory organ that has differing effects on metabolic disease depending upon location and composition. Resting beneath the fascia, and bordering muscle fibers, intermuscular adipose tissue (IMAT) secretes proteins and lipid signaling molecules that are uniquely positioned to directly impact insulin sensitivity and inflammation in skeletal muscle. Individuals with Obesity and type 2 diabetes have increased IMAT volume, and while IMAT is inversely correlated with muscle strength, function, and insulin sensitivity, the mechanisms by which it exerts these effects are unknown. We quantified the secretome of IMAT, subcutaneous adipose tissue (SAT), and visceral adipose tissue (VAT) to determine if there are differences between depots in the secretion of cytokines, eicosanoids, FFAs and proteins that influence metabolic function. SAT and VAT biopsies from bariatric surgery patients and IMAT from the vastus lateralis biopsies of individuals with Obesity were cultured for 48 hours in DMEM, and the conditioned media was analyzed using nanoflow HPLC-MS, multiplex ELISAs and LC/MS/MS for proteins, cytokines and eicosanoids/FFA, respectively. IMAT secretion of various extracellular matrix proteins was significantly different than VAT and SAT. Pro-inflammatory cytokine secretion of IFNγ, TNFα, IL-8 and IL-13 from IMAT was higher than VAT and significantly higher than SAT (p < 0.05). IMAT secretes significantly more pro-inflammatory eicosanoids TXB2 and PGE2 than VAT (p = 0.02, 0.05) and SAT (p = 0.01, 0.04). IMAT and VAT have significantly greater basal lipolysis assessed by FFA release rates compared to SAT (p = 0.01, 0.04). These data begin to characterize the disparate secretory properties of SAT, VAT and IMAT that may impact tissue function, and suggest that the metabolically adverse secretome of IMAT, with such proximity to skeletal muscle may play an important functional role in the pathogenesis of insulin resistance and type 2 diabetes.
D.E. Kahn: None. E. Macias: None. S. Zarini: None. K.A. Harrison: None. M. Cree-Green: None. B.C. Bergman: Advisory Panel; Spouse/Partner; AstraZeneca, Merck & Co., Inc., Novo Nordisk Inc.
National Institutes of Health (R01DK118149, RR-00036); Colorado Nutrition Obesity Research Center (P30DK048520)