Leptin replacement prevents weight loss-induced metabolic adaptation in congenital leptin-deficient patients.
BACKGROUND
Leptin regulates energy homeostasis by suppressing food intake; however, its role in energy expenditure and fat oxidation remains uncertain in humans.


OBJECTIVE
The aim of the study was to assess 24-h energy metabolism before and after weight loss induced by leptin treatment in congenital leptin-deficient subjects or low-calorie diet in controls.


METHODS
We measured 24-h energy expenditure, 24-h fat oxidation, and body fat in three null homozygous leptin-deficient obese adults before and after weight loss induced by a 19-wk leptin replacement period (0.02-0.04 mg/kg/d). The same measures were performed in three obese controls pair-matched for sex, age, and weight loss induced by a 10- to 21-wk low-calorie diet. Measurements were preceded for 1 wk of weight stabilization. Energy expenditure was adjusted for fat-free mass, fat mass, sex, and age based on a reference population (n = 842; R(2) = 0.85; P < 0.0001). Similarly, fat oxidation was adjusted for fat-free mass, percentage body fat, energy balance, and diet composition during the 24-h respiratory chamber stay (R(2) = 0.38; P < 0.0001).


RESULTS
Before weight loss, congenital leptin-deficient and control subjects had similar energy expenditure. However, after weight loss ( approximately 15 kg), controls had energy expenditures lower than expected for their new weight and body composition (-265 +/- 76 kcal/d; P = 0.04), whereas leptin-treated subjects had values not different from the reference population (-128 +/- 119 kcal/d; P = 0.67). Before weight loss, fat oxidation was similar between groups. However, after weight loss, leptin-treated subjects had higher fat oxidation than controls (P = 0.005) and higher than the reference population (P = 0.0001).


CONCLUSIONS
In congenital leptin-deficient subjects, leptin replacement prevented the decrease in energy expenditure and fat oxidation often observed after weight loss.
Galgani
Jose E
JE
Pennington Biomedical Research Center, 6400 Perkins Road, Baton Rouge, Louisiana 70808, USA.
Greenway
Frank L
FL
Caglayan
Sinan
S
Wong
Ma-Li
ML
Licinio
Julio
J
Ravussin
Eric
E
D000222:Adaptation, Physiological; D000273:Adipose Tissue / Q000378:metabolism; D000328:Adult; D001823:Body Composition; D004734:Energy Metabolism; D005260:Female; D020249:Hormone Replacement Therapy; D006801:Humans; D020738:Leptin / Q000097:blood / Q000172:deficiency* / Q000627:therapeutic use*; D008297:Male; D010084:Oxidation-Reduction; D015431:Weight Loss / Q000502:physiology*
D020738:Leptin