Hyperleptinemia: an early manifestation of juvenile obesity.
relations to body fat depots and insulin concentrations.
Caprio, S., W. V. Tamborlane, D. Silver, C. Robinson, R. Leibel, S.
McCarthy, A. Grozman, A. Belous, D. Maggs, and R. S. Sherwin.
Departments of Pediatrics, Internal Medicine, Diagnostic Radiology
and the Yale Children's and General Clinical Research Center, Yale
University School of Medicine, New Haven, CT 06520. Laboratory of
Human Behavior and Metabolism, Rockefeller University, New York, NY
10021, USA
APStracts 3:0128E, 1996.
Leptin, the OB gene product, is an adipocyte-derived circulating
protein. In several rodent models of obesity such as the db/db,
fa/fa, VMH-lesioned as well as adult obese subjects, leptin mRNA
expression and the circulating levels are elevated, suggesting
resistance to its action. However, it is unknown whether the rise in
leptin concentration occurs early in the natural evolution of human
obesity or is a chronic adaptation to the obese state. Moreover,
whether the distribution of body fat (i.e., visceral vs subcutaneous
abdominal fat) influences circulating leptin levels has not been
assessed. We have determined in a group of obese and non-obese
children and young adults whether leptin levels a) are increased
early in the development of obesity, b) are related to a specific fat
depot measured by magnetic resonance imaging, c) vary during
hyperinsulinemic euglycemic and hyperglycemic clamp studies, and d)
are different in males vs females. In the basal state, leptin levels
were elevated in obese children. Children and adults demonstrated a
strong positive correlation between leptin concentrations and the
subcutaneous fat depot (r=0.84, p<0.001). Surprisingly, a weaker
correlation was found with visceral fat mass (r=0.59, p=0.001).
Leptin levels remained unchanged under both euglycemic and
hyperglycemic hyperinsulinemic conditions in both obese and non-obese
subjects. A pronounced effect of gender on leptin levels was also
observed. We conclude that early in the development of juvenile
obesity leptin concentrations are elevated and are more closely
linked to subcutaneous than visceral fat mass. Acute increases in
insulin concentrations do not affect circulating leptin levels.
Received 2 April 1996; accepted in final form 12 June 1996.
APS Manuscript Number E164-6.
Article publication pending Am. J. Physiol. (Endocrinol. Metab.).
ISSN 1080-4757 Copyright 1996 The American Physiological Society.
Published in APStracts on 25 July 1996