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Cited by 74Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesHypothalamic control of reproductive hormones

The Effects of Leptin Administration in Non‐obese Human Subjects

Mackintosh, Ronald M., Hirsch, Jules·2001·Obesity Research
DOI 10.1038/oby.2001.60
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Abstract

Objective: Body fatness is partly under hypothalamic control with effector limbs that include the endocrine system and the autonomic nervous system (ANS). In previous studies of both obese and never‐obese subjects, we have shown that weight increase leads to increased sympathetic and decreased parasympathetic activity, whereas weight decrease leads to decreased sympathetic and increased parasympathetic activity. We now report on the effect of leptin, independent of weight change, on the ANS. Research Methods and Procedures: Normal weight males (ages 20–40 years) were fed a solid food diet, measured carefully to maintain body weight, for 3 weeks, as inpatients at the Rockefeller University General Clinical Research Center. In a single‐blind, 22‐day, placebo/drug/placebo design, six subjects received leptin 0.3 mg/kilogram subcutaneously for 6 days. ANS measures of amount of parasympathetic control and sympathetic control of heart period (interbeat interval) were made by sequential pharmacological blockade with intravenous atropine and esmolol. Norepinephrine, dopamine, and epinephrine levels in 24‐hour urine collections were also measured as well as resting metabolic rate. Results: Sufficient food intake maintained constant body weight in all subjects. There was no evidence that leptin administration led to changes in energy metabolism sufficient to require additional food intake or to alter resting metabolic rate. Likewise, leptin administration did not alter autonomic activity. Parasympathetic control and sympathetic control, as well as the urinary catecholamines, were not significantly affected by leptin administration. Glucose and insulin levels were increased by food intake as expected, but leptin had no affect on these levels before or after food intake. Discussion: ANS responses to changes in energy metabolism found when food intake and body weight are altered were not found in these never‐obese subjects given leptin for 6 days. Although exogenous leptin administration has profound effects on food intake and energy metabolism in animals genetically deprived of leptin, we found it to have no demonstrable effect on energy metabolism in never‐obese humans. The effects of longer periods of administration to obese individuals and to those who have lost weight demand additional investigation.

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  • Our findings are in agreement with a previous study in nonobese men on an isocaloric diet in whom leptin administration (0.3 mg/kg per day) for 6 days had no effect on autonomic activity or urinary catecholamines.

    “Our findings are in agreement with a previous study in nonobese men on an isocaloric diet in whom leptin administration (0.3 mg/kg per day) for 6 days had no effect on autonomic activity or urinary catecholamines (52).”

    From The role of falling leptin levels in the neuroendocrine and metabolic adaptation to short-term starvation in healthy men (2003) · cites this paper as [52]

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Authors
Mackintosh, R. M., & Hirsch, J.
Affiliations
Rockefeller University (US)
Corresponding author
Hirsch, Jules
Venue
Obesity Research
Publisher
Wiley
Published
2001-08
Volume
9
Issue
8
Pages
462-469
ISSN
  • 1071-7323 (ISSN-L)
  • 1550-8528
DOI
10.1038/oby.2001.60
OpenAlex
W1981452149
Cited by
74
References
15
Citations by year
2025: 1 · 2023: 2 · 2022: 2 · 2021: 2 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 4 · 2016: 2 · 2015: 2 · 2014: 5 · 2013: 1 · 2012: 2
FWCI
1.66
Type
journal article
Language
en
Open access
closed
Licence
onlinelibrary.wiley.com/termsAndConditions#vor (vor, 4054 d)
Locations
  • Obesity Research (publishedVersion)
  • PubMed (publishedVersion)
Funders
  • National Institutes of Health (2m01rr000102-41)
  • National Center for Research Resources (M0-1 RR00102)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Health Sciences › Medicine › Reproductive Medicine › Hypothalamic control of reproductive hormones
Keywords
leptin, autonomic nervous system, sympathetic activity, parasympathetic activity, heart period, resting metabolic rate, energy metabolism, dietary intake, urinary catecholamines, norepinephrine, dopamine, epinephrine, non-obese patients
MeSH terms
Adult, Autonomic Nervous System, Basal Metabolism, Blood Pressure, Catecholamines, Energy Metabolism, Humans, Injections, Subcutaneous, Male, Body Mass Index, Leptin

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