The effects of angiotensin-II on lipolysis in humans.
Adipocytes express many of the proteins of the renin-angiotensin system including angiotensinogen and AT(1)-receptors. A principal function of adipocyte tissue is the provision of energy substrate through lipolysis. This study was undertaken to determine if angiotensin-II (Ang-II) infusion or blockade of the renin-angiotensin system by angiotensin-converting enzyme (ACE) inhibitor therapy with enalapril altered lipolytic activity and substrate oxidation. Eleven healthy male subjects were enrolled in the first study and postabsorptive whole-body lipolysis activity was measured using a stable isotope of glycerol ((2)H(5)-glycerol). Substrate oxidation was determined using indirect calorimetry in the Clinical Research Center. Subjects were then sequentially treated with low-dose Ang-II infusion (0.3 and then 1.0 ng/kg/min) on separate days, and the lipolysis and oxidation studies were repeated. Lastly, each subject was treated with 2 weeks of ACE inhibitor with enalapril (20 mg daily) and underwent lipolysis and oxidation studies for a fourth time. In a second study, 14 healthy male subjects were enrolled and underwent an identical baseline lipolysis and substrate oxidation assessment. These subjects then received an Ang-II infusion at pressor doses (10 ng/kg/min), and changes in lipolytic activity and substrate oxidation were measured again. In the first study, there was no effect on lipolysis activity from low-dose Ang-II infusion (baseline lipolysis activity (mean +/- SD) 2.06 +/- 0.55 micromol/kg/min, 2.10 +/- 0.69 micromol/kg/min after 0.3 ng/kg/min, and 2.32 +/- 0.56 micromol/kg/min after 1.0 ng/kg/min) or enalapril therapy (2.35 +/- 1.00 micromol/kg/min). In the second study, the larger dose of Ang-II increased blood pressure by 14/17 mm Hg, but there was no effect on lipolysis activity (1.36 +/- 0.49 micromol/kg/min v 1.63 +/- 0.82 micromol/kg/min). Substrate oxidation rates were largely unaffected by Ang-II infusions or enalapril therapy. There was no evidence that treatment with subpressor or pressor dosages of Ang-II produced a significant alteration in lipolytic activity. Moreover, blockade of the renin-angiotensin system with enalapril was equally unremarkable in its effects on whole-body lipolysis. These data support the general concept that the renin-angiotensin system in adipocytes serves more to regulate the regional blood flow to adipose tissue and the size and number of fat cells rather than participating directly in the regulation of energy substrate.
Townsend
R R
RR
Department of Medicine, University of Pennsylvania, Philadelphia 19104, USA.
D000328:Adult; D000804:Angiotensin II / Q000494:pharmacology*; D000806:Angiotensin-Converting Enzyme Inhibitors / Q000494:pharmacology; D001794:Blood Pressure / Q000187:drug effects; D050260:Carbohydrate Metabolism; D002395:Catecholamines / Q000097:blood; D004656:Enalapril / Q000494:pharmacology; D004734:Energy Metabolism / Q000502:physiology; D006801:Humans; D050356:Lipid Metabolism; D008066:Lipolysis / Q000187:drug effects*; D008297:Male; D010084:Oxidation-Reduction; D012083:Renin / Q000097:blood
D000806:Angiotensin-Converting Enzyme Inhibitors; D002395:Catecholamines; D000804:Angiotensin II; D004656:Enalapril; D012083:Renin