Interactions between leptin and the human sympathetic nervous system by monkey6


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									Interactions between leptin and the human sympathetic nervous system.

Eikelis N et al.
Hypertension 2003; 41: 1072-1079.

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Rationale: Leptin released from adipose tissue in proportion to fat cell mass,
regulates fat mass by acting within the brain to reduce food intake and to increase
energy expenditure. This increase in energy expenditure is mediated by the
activation of the sympathetic nervous system by leptin. Long-term regulators of leptin
synthesis and release have been identified as being adiposity and gender. The
sympathetic nervous system has been suggested to be a short-term regulator,
whereby the catecholamines, noradrenaline and adrenaline, inhibit the release of
leptin. Consequently it has been suggested that a 2-way interaction exists between
leptin and the sympathetic nervous system which may constitute a regulatory
feedback loop, with leptin enhancing sympathetic nervous system outflow which in
turn inhibits leptin release. The aim of this study was to determine whether such a 2-
way interaction exists in human subjects.

Methods: Arterial plasma leptin concentrations were measured in clinical models of
enhanced sympathetic tone such as heart failure (n=70), essential hypertension
(n=26) and pure autonomic failure (n=5) and compared to measurements obtained in
62 healthy volunteers. In addition within the 62 healthy volunteers comparisons of
leptin measurements were made between persons >60 years (aging as a clinical
model of reduced adrenaline secretion) and persons <35 years of age. Comparisons
were also made between obese (BMI >28 kg/m 2) and lean (BMI < 26 kg/m2)
otherwise healthy volunteers.

Renal leptin clearance was determined by renal vein catherization in order to ensure
that alterations in plasma concentration were not as a consequence of changes in
renal clearance of leptin.

To test for a possible stimulation of the sympathetic nervous system by leptin,
measures of regional sympathetic activity (isotope dilution measures of whole body,
renal and cardiac noradrenaline spill over rates) were interrelated with plasma leptin
concentrations over a range of varying adiposities.

Pharmacological alterations in sympathetic activity where determined by intravenous
infusion of nitroprusside (directly acting vasodilator hence activating the sympathetic
nervous system) in 11 patients with cardiac failure, and by intravenous infusions of
clonidine (a centrally acting inhibitor of sympathetic outflow) in 9 patients with cardiac
Findings: As expected total noradrenaline spill over was increased in the clinical
models of enhanced sympathetic tone (heart failure and hypertension). However
leptin concentrations were elevated in the patients with heart failure and
hypertension, rather than suppressed. This elevation was as a consequence of a
lower renal clearance of leptin which was due to a reduced renal plasma flow in the
patients with heart failure. There was a tendency for the hypertensive patients to also
have a reduction in renal clearance of leptin.

Patients with pure autonomic failure had reduced total noradrenaline spill over
however leptin concentrations were not elevated.

With respect to aging effects, the secretion of adrenaline was substantially reduced
but leptin was only marginally higher.

Despite expected changes in noradrenaline spill over with pharmacological
modifications leptin concentrations were not altered.

Leptin concentrations were increased in obese versus lean healthy subjects. These
increases were not due to alterations in renal leptin clearance. Furthermore a
correlation between renal noradrenaline spill over and arterial leptin concentration
was observed in these subjects.

Interpretation: Using various models of either elevated sympathetic tone or reduced
sympathetic nervous system activity, no alterations in leptin concentrations were
observed. Hence it is unlikely that sympathetic nervous system activity regulates the
release of leptin from adipose tissue. However the data from this study was able to
support the hypothesis that leptin stimulates the sympathetic nervous system.

                                                               Prof Angela Woodiwiss

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