In obesity the endogenous inhibitor of lipolysis, adenosine, may be increased as a mechanism to increase blood flow and decrease intracellular lipolysis in order to limit the accumulation of fatty acids in the interstitium. Pharmacological and physiological stimulation of lipolysis via isoprenaline (ISO) and exercise, respectively, are commonly used means of studying lipolysis. However, the in-vivo effects of adenosine on these modes of stimulation are not well-known. PURPOSE: To determine the effects of adenosine on lipolysis under resting and exercise conditions. METHODS: We measured in-vivo lipolysis (interstitial glycerol levels) via microdialysis of subcutaneous abdominal adipose tissue (SCAAT) in 16 obese premenopausal women (29±4.7 yrs, BMI= 40.1±9.3kg/m2). Three microdialysis probes were perfused with: 1) control solution (Saline), 2) DPCPX (A1 adenosine receptor antagonist), or 3) 2-chloro-adenosine (2CA, adenosine receptor agonist) with and without local pharmacological stimulation by ISO. RESULTS: Local infusion of 2CA significantly reduced SCAAT glycerol concentrations (-11.5±4.9%, P = 0.013) compared to basal levels while local DPCPX infusion increased glycerol concentrations (11.8±4.7%, P = 0.055) compared to basal. The decreased glycerol concentration with 2CA at rest was abolished with inhibition of nitric oxide synthase using a co-infusion of 2CA and L-NMMA (5.3±4.6%, P = 0.51 vs basal and -11.5±4.9%, P = 0.015 vs 2CA alone). 2CA infusion also reduced the ISO stimulated increase in dialysate glycerol concentration (142.0±18.2% ISO alone vs. 74.7±12.5% ISO+ 2CA, P = 0.012). Exercise (30 min cycle ergometry at 60% VO2peak) resulted in a 64% increase in lipolysis above ISO alone with no differential effects of local infusions of 2CA or DPCPX (64.1±7.8% 2CA and 64.8±9.6% DPCPX, P = 0.920) on this increase. No differences in ethanol outflow/inflow ratio (index of local tissue blood flow) between probes or treatments during microdialysis were observed. CONCLUSION: Adenosine decreases resting and ISO-stimulated lipolysis in-vivo. However, adenosine does not inhibit maximally stimulated lipolysis via ISO and exercise combined. The endogenous lipolytic inhibitor, nitric oxide, may be a mechanism through which adenosine reduces lipolysis in-vivo. Supported by NIDDK 1R15DK074401.
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