(OR10-02-25) The Effect of Leptin Phenotypes on Weight Change and Energy Expenditure Responses to Acute and Prolonged Positive or Negative Energy Balance

Objectives: Leptin plays a role in regulating energy homeostasis and body mass. Despite its close correlation with adipose tissue mass, there is substantial variability in circulating leptin among people with similar adiposity. Recently, distinct “leptin phenotypes” characterized by high or low leptin concentration relative to body fat have been shown to explain differences in cardiometabolic risk factors. These phenotypes present an opportunity to test whether relatively high vs low leptin concentrations differentially affect the energy homeostasis response to perturbations of energy balance.

Methods: To test this hypothesis, we compared energy expenditure and weight change responses between the leptin phenotypes using four distinct experimental designs; 1) cross-sectional data of the Pennington Nutrition and Obesity Research Center (NORC) repository (N=104), 2) prospective data following 24-hour acute over- and underfeeding (N=77), 3) prospective data following prolonged over- and underfeeding via 24-month caloric restriction (N=144) and 4) 8-week overfeeding (N=28). Leptin phenotypes were defined based on the residuals of the sex-specific cubic fit between body fat percentage and plasma leptin concentration; individuals were classified as having relatively low or high leptin if they fell below or above the median value of the residuals’ distribution, respectively.

Results: There was no evidence of leptin phenotypes explaining variation in energy expenditure cross-sectionally, and leptin phenotypes were similarly not associated with differential metabolic adaptation when explored longitudinally across both acute and prolonged interventions. Moreover, leptin phenotype was not associated with weight change in response to energy restriction or surplus.

Conclusions: These results challenge the hypothesis that chronic exposure to relatively higher or lower leptin concentrations for any given level of body fat contributes to meaningful interindividual differences in regulation of energy expenditure and resulting body mass.

Funding Sources: National Institute on Aging; National Institutes of Health Cooperative Agreements; National Institute of Diabetes and Digestive and Kidney Diseases; Pennington/Louisiana Nutrition and Obesity Resource Center.