Low dose leptin administration reverses effects of sustained weight-reduction on energy expenditure and circulating concentrations of thyroid hormones.
Maintenance of a reduced body weight is associated with decreased 24-hour energy expenditure, and decreased circulating concentrations of leptin and thyroid hormones. To determine whether these adaptive metabolic and endocrine changes are partly leptin-mediated, we measured body composition, aspects of energy expenditure, and circulating concentrations of leptin and thyroid hormones in 4 subjects at 3 time points: 1.) Usual body weight; 2.) While stable at 10% reduced body weight; and 3.) During a 5-week period at 10% reduced body weight while receiving twice per day leptin injections that restored 8 AM circulating leptin concentrations to those seen at usual body weight. During maintenance of a 10% reduced body weight, circulating T3, T4, and leptin concentrations were decreased. All of these endocrine changes were reversed by administration of "replacement" doses of leptin (r-metHuLeptin). Indirect calorimetry, and subtle changes in body composition associated with leptin administration, were used to calculate the net change in stored calories and in 24-hour energy expenditure. Total energy expenditure increased in all subjects during r-metHuLeptin administration. These data indicate that decrease leptin concentrations resulting from loss of fat mass account for some aspects of the endocrine/metabolic phenotype associated with the weight-reduced state.
Rosenbaum
Michael
M
Columbia University, New York, New York, USA.
Murphy
Ellen M
EM
Heymsfield
Steven B
SB
Matthews
Dwight E
DE
Leibel
Rudolph L
RL
D000328:Adult; D001823:Body Composition / Q000187:drug effects; D002153:Calorimetry, Indirect; D004305:Dose-Response Relationship, Drug; D004734:Energy Metabolism / Q000187:drug effects*; D005260:Female; D006801:Humans; D020738:Leptin / Q000008:administration & dosage* / Q000031:analogs & derivatives* / Q000097:blood / Q000494:pharmacology; D008297:Male; D009994:Osmolar Concentration; D013963:Thyroid Hormones / Q000097:blood*; D015431:Weight Loss / Q000502:physiology*
D020738:Leptin; D013963:Thyroid Hormones; C122136:recombinant methionyl human leptin