In central obesity, weight loss restores platelet sensitivity to nitric oxide and prostacyclin.
Central obesity shows impaired platelet responses to the antiaggregating effects of nitric oxide (NO), prostacyclin, and their effectors--guanosine 3',5'-cyclic monophosphate (cGMP) and adenosine 3',5'-cyclic monophosphate (cAMP). The influence of weight loss on these alterations is not known. To evaluate whether a diet-induced body-weight reduction restores platelet sensitivity to the physiological antiaggregating agents and reduces platelet activation in subjects affected by central obesity, we studied 20 centrally obese subjects before and after a 6-month diet intervention aiming at reducing body weight by 10%, by measuring (i) insulin sensitivity (homeostasis model assessment of insulin resistance (HOMA(IR))); (ii) plasma lipids; (iii) circulating markers of inflammation of adipose tissue and endothelial dysfunction, and of platelet activation (i.e., soluble CD-40 ligand (sCD-40L) and soluble P-selectin (sP-selectin)); (iv) ability of the NO donor sodium nitroprusside (SNP), the prostacyclin analog Iloprost and the cyclic nucleotide analogs 8-bromoguanosine 3',5'-cyclic monophosphate (8-Br-cGMP) and 8-bromoadenosine 3',5'-cyclic monophosphate (8-Br-cAMP) to reduce platelet aggregation in response to adenosine-5-diphosphate (ADP); and (v) ability of SNP and Iloprost to increase cGMP and cAMP. The 10 subjects who reached the body-weight target showed significant reductions of insulin resistance, adipose tissue, endothelial dysfunction, and platelet activation, and a significant increase of the ability of SNP, Iloprost, 8-Br-cGMP, and 8-Br-cAMP to reduce ADP-induced platelet aggregation and of the ability of SNP and Iloprost to increase cyclic nucleotide concentrations. No change was observed in the 10 subjects who did not reach the body-weight target. Changes of platelet function correlated with changes of HOMA(IR). Thus, in central obesity, diet-induced weight loss reduces platelet activation and restores the sensitivity to the physiological antiaggregating agents, with a correlation with improvements in insulin sensitivity.
Russo
Isabella
I
Department of Clinical and Biological Sciences, Internal Medicine Unit, University of Turin, San Luigi Gonzaga Hospital, Orbassano, Italy.
Traversa
Monica
M
Bonomo
Katia
K
De Salve
Alessandro
A
Mattiello
Luigi
L
Del Mese
Paola
P
Doronzo
Gabriella
G
Cavalot
Franco
F
Trovati
Mariella
M
Anfossi
Giovanni
G
D000244:Adenosine Diphosphate / Q000494:pharmacology; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001792:Blood Platelets / Q000187:drug effects*; D000242:Cyclic AMP / Q000378:metabolism; D006152:Cyclic GMP / Q000378:metabolism; D004038:Diet, Reducing; D004730:Endothelium, Vascular / Q000503:physiopathology; D011464:Epoprostenol / Q000494:pharmacology; D005260:Female; D006801:Humans; D016285:Iloprost / Q000494:pharmacology; D007333:Insulin Resistance; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D009599:Nitroprusside / Q000494:pharmacology; D056128:Obesity, Abdominal / Q000178:diet therapy / Q000503:physiopathology*; D015539:Platelet Activation / Q000187:drug effects*; D010975:Platelet Aggregation Inhibitors / Q000494:pharmacology*; D015431:Weight Loss / Q000502:physiology*
D010975:Platelet Aggregation Inhibitors; D009599:Nitroprusside; D009569:Nitric Oxide; D000244:Adenosine Diphosphate; D011464:Epoprostenol; D000242:Cyclic AMP; D006152:Cyclic GMP; D016285:Iloprost