title: Differential effects of local versus systemic angiotensin II in the regulation of leptin release from adipocytes.
abstract: Adipocytes secrete a variety of factors, including angiotensinogen, the only known precursor to Angiotensin II (AngII). Recent studies suggest that adipocyte-derived angiotensinogen can contribute to circulating angiotensinogen concentrations and modulate blood pressure; however, an autocrine role for adipocyte-derived angiotensinogen and/or AngII has not been well defined. We sought to determine whether locally produced AngII influences the release of leptin from adipocytes and thus circulating leptin concentrations. In adipocytes from rats treated for 3 d with captopril demonstrating reductions in AngII release, leptin release and plasma leptin concentration were decreased. Incubation of adipocytes with AngII resulted in an increase in leptin mRNA expression and leptin release. To determine the effect of elevated systemic AngII on leptin, rats were infused with AngII (175 ng/kg.min) or saline for 1, 2, or 7 d. Plasma leptin concentration progressively declined with duration of AngII exposure. Basal and AngII-stimulated release of leptin from isolated adipocytes was initially (d 1) increased in AngII-infused rats; thereafter leptin release declined to levels less than control. To define mechanisms for declines in leptin in AngII-infused rats, we examined the effect of alpha-methyl-p-tyrosine on catecholamine turnover and plasma leptin concentration in saline- and AngII (175 ng/kg.min)-infused rats. Infusion of AngII increased catecholamine turnover in adipose tissue. Moreover, sympathetic blockade eliminated differences in plasma leptin concentration between saline- and AngII-infused rats. These results indicate that locally produced AngII directly increases leptin release from adipocytes; however, with elevations in systemic AngII, sympathetic activation counterbalances effects from locally produced AngII.
mesh_terms: D017667:Adipocytes / Q000187:drug effects* / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D000818:Animals; D002216:Captopril / Q000494:pharmacology; D020738:Leptin / Q000097:blood* / Q000235:genetics; D008297:Male; D009638:Norepinephrine / Q000378:metabolism; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013564:Sympathetic Nervous System / Q000502:physiology; D014662:Vasoconstrictor Agents / Q000494:pharmacology*
chemical_list: D000806:Angiotensin-Converting Enzyme Inhibitors; D020738:Leptin; D012333:RNA, Messenger; D014662:Vasoconstrictor Agents; D000804:Angiotensin II; D002216:Captopril; D009638:Norepinephrine