Leptin levels in humans are acutely suppressed by isoproterenol despite acipimox-induced inhibition of lipolysis, but not by free fatty acids

Citation
M. Stumvoll et al., Leptin levels in humans are acutely suppressed by isoproterenol despite acipimox-induced inhibition of lipolysis, but not by free fatty acids, METABOLISM, 49(3), 2000, pp. 335-339
Citations number
24
Categorie Soggetti
Endocrinology, Nutrition & Metabolism
Journal title
METABOLISM-CLINICAL AND EXPERIMENTAL
ISSN journal
00260495 → ACNP
Volume
49
Issue
3
Year of publication
2000
Pages
335 - 339
Database
ISI
SICI code
0026-0495(200003)49:3<335:LLIHAA>2.0.ZU;2-N
Abstract
Leptin secretion is complexly regulated in humans. Insulin has been shown t o stimulate leptin secretion, whereas in vitro data suggest that catecholam ines and free fatty acids (FFAs) inhibit leptin secretion. To dissect diffe rential effects on leptin secretion, we performed two experimental protocol s in 11 lean healthy subjects in addition to a saline infusion plus oral ac ipimox to suppress lipolysis (SAL + ACX) as a control experiment: (1) isopr oterenol (similar to 30 ng/kg . min, to increase the heart rate by similar to 50 bpm) plus oral acipimox (ISO + ACX, 240 minutes) and (2) Intralipid ( Pharmacia & Upjohn, Erlangen, Germany) plus heparin (LIP, 420 minutes). Dur ing SAL + ACX, FFAs decreased from 0.44 +/- 0.04 to 0.06 +/- 0.02 mmol/L (P = .001), while serum insulin and leptin remained unchanged. During ISO + A CX, FFAs decreased similarly from 0.41 +/- 0.13 to 0.09 +/- 0.02 mmol/L (P = .001), while insulin increased from 47 +/- 8 to a maximum of 116 +/- 15 p mol/L (P = .001) and serum leptin decreased acutely from 6.4 +/- 2.1 to a m inimum of 5.4 +/- 1.8 ng/mL after 90 minutes (P = .003 vSAL + ACX). After 1 50 minutes, leptin returned to control levels. During LIP, the elevation of FFAs from 0.34 +/- 0.04 to 1.71 +/- 0.19 mmol/L (P = .001) had no effect o n serum insulin or leptin concentrations (both P = nonsignificant). In conc lusion, our results show that in humans, isoproterenol acutely suppresses l eptin levels independently of increased FFAs, and elevated FFAs have no acu te effect on leptin levels. The fact that an inhibition of leptin secretion occurred despite conditions that are known to suppress intracellular cycli c adenosine monophosphate (cAMP) levels, as demonstrated by suppressed lipo lysis, suggests that signaling mechanisms other than those mediated by cAMP must be involved in modulating leptin secretion. Copyright (C) 2000 by W.B . Saunders Company.