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Mechanisms underlying the direct effects of exercise on metabolic health (independently of weight loss) are poorly understood, and very little is known about the effects of exercise on adipose tissue. The purpose of this study was to examine the effects of exercise training on the key extracellular matrix (ECM) modifiers, matrix metalloproteinase 2 (MMP2) and MMP9, in abdominal subcutaneous adipose tissue (aSAT) of obese adults. Seven obese adults (BMI=33±4 kg/m2; age=32±6) completed 12 weeks of exercise training (either 45min of steady-state exercise at 70% HRmax or 10x1min intervals at 90% HRmax with 1min recovery between intervals), and they were required to maintain body weight throughout. aSAT biopsies were collected before training (Pre) and twice after training - 1 day post exercise (1d PEX) and again 4 days post exercise (4d PEX; to wash out the acute effects of exercise). Using standard immunoblotting methods, we found no evidence for effects of training on either MMP2 or MMP9. However, using gelatin zymography (a technique with more than 100-fold higher sensitivity than immunoblotting) we found a strong trend for an increased MMP9 abundance 1d PEX (3.7±1.0 vs. 3.0±1.4 arbitrary units (AU), for 1d PEX vs. Pre; P=0.08). Interestingly, however, MMP9 returned to Pre training levels by 4d PEX (1.9±1.3 AU; P In summary, because increased abundance and activity of MMPs may alter the fibrotic content and composition of the ECM, exercise-induced increases in MMP2 and MMP9 within aSAT may contribute to favorable modifications within adipose tissue ECM of obese adults. Disclosure P. Varshney: None. B.J. Ryan: None. C. Ahn: None. M.W. Schleh: None. J.F. Horowitz: None. Funding National Institutes of Health (R01DK077966, P30DK089503, F32DK117522, UL1TR002240)

Many metabolic health complications in obese adults are linked to abnormalities within their enlarged adipose tissue mass, which include hypertrophic adipocytes, a fibrotic extracellular matrix (ECM), and suppressed capillary density. Exercise training is a first-line treatment for obesity-related diseases, but the direct effects of exercise on adipose tissue structure and metabolic function remain unclear. The purpose of this study was to determine the effects of moderate-intensity continuous training (MICT) and high-intensity interval training (HIIT) on subcutaneous adipose tissue morphology. 17 obese adults were randomly assigned to 12 weeks (4 days/week) of MICT (45 minutes at 70% HRmax, n=9) or HIIT (10 X 1 minutes at 90% HRmax, 1 minute recovery, n=8) and were required to maintain their body weight throughout. Abdominal subcutaneous adipose tissue biopsy samples were collected before and after training for histological and immunoblot measures to assess adipocyte cell size, markers of ECM remodeling and capillarization. Aerobic fitness (VO2peak) improved ∼10% in both MICT and HIIT (P In summary, exercise training, perhaps especially HIIT, may increase adipogenic and angiogenic capacity in adipose tissue, as well as trigger adipose ECM remodeling. Disclosure C. Ahn: None. B.J. Ryan: None. J.B. Gillen: None. A. Ludzki: None. M.W. Schleh: None. B.A. Reinheimer: None. J.F. Horowitz: Research Support; Self; American Diabetes Association. Funding National Institutes of Health (R01DK077966, P30DK089503, T32DK007245); Canadian Institutes of Health Research (DFS146190)

High body iron stores are positively related to insulin resistance in humans, but the underlying mechanisms remain unresolved. Iron stimulates lipolysis in murine adipocytes in vitro, but the influence of iron stores on lipolytic rate in vivo is unknown. Our aim was to determine if body iron stores are associated with lipolytic rate and whole-body insulin sensitivity in obese, pre-menopausal women. We studied 20 subjects with clinically-normal (20-200 ng/mL) plasma [ferritin], an index of body iron stores. Fatty acid rate of appearance into systemic circulation (FA Ra) was assessed by 13C-palmitate isotope dilution, insulin resistance was assessed by hyperinsulinemic-euglycemic clamp, and abdominal subcutaneous adipose tissue protein expression was assessed via immunoblot. [Ferritin] was significantly (p < 0.01), positively correlated with FA Ra (r2 = 0.42), adipose hormone sensitive lipaseser660 phosphorylation (p-HSLser660, a marker of lipolytic activation in adipose tissue; r2 = 0.41), and whole-body insulin resistance (r2 = 0.33). Importantly, [ferritin] remained a significant, independent predictor for these parameters in multiple regression models including body mass index, plasma [adiponectin], and plasma [CRP] as covariates. We stratified subjects into tertiles based on [ferritin] to compare high-normal and low-normal [ferritin] groups (138 ± 30 vs. 40 ± 15 ng/mL). Compared with the low-normal [ferritin] group, the high-normal [ferritin] group had significantly (p < 0.02) higher FA Ra (15.6 ± 5.5 vs. 8.8 ± 2.4 µmol/kg fat mass/min), adipose p-HSLser660 (1.3 ± 0.4 vs. 0.6 ± 0.2 AU) and whole-body insulin resistance (glucose infusion rate 9.2 ± 2.3 vs. 14.3 ± 3.5 mg/kg fat free mass/min). There were no between-group differences in anthropometric characteristics, plasma [adiponectin], or plasma [CRP]. Our findings suggest that iron-mediated activation of adipose lipolysis may be a mechanism linking body iron stores and insulin resistance in obese humans. Disclosure B.J. Ryan: None. D.W. Van Pelt: None. L.M. Guth: None. A. Ludzki: None. R.A. Gioscia-Ryan: None. C. Ahn: None. J.F. Horowitz: None.