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
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.