ESPE Yearbook of Paediatric Endocrinology

Brief Summary: This study compared 2 groups of adults defined by their leptin concentrations relative to fat mass. Adults with ‘relatively high leptin’ (RHL, n=646) or ‘relatively low leptin’ (RLL, n=644) concentrations were compared in insulin concentration, insulin secretion, and insulin sensitivity, at both the whole-body level and within adipose tissue. Individuals with RHL showed a distinct metabolic phenotype, characterized by insulin resistance in both whole-body glucose metabolism and adipose tissue lipolysis, regardless of their degree of adiposity.

There is a high variability in leptin concentrations between individuals with the same BMI or fat mass. Whether individuals with RHL or RLL differ in terms of their metabolic phenotype and response to interventions is of clinical interest. As there are no reference values for leptin concentrations that cover the entire BMI spectrum in adults, the authors used a sex-specific leptin-fat mass regression within the studied cohort to categorise adults as having RLL or RHL. In another study, Akinci et al. grouped adults with leptin concentrations <25th percentile of NHANES III population based on sex and BMI as RLL and adults with leptin concentrations >75th percentile as RHL (1). Potential therapeutic consequences of RLL were suggested by Akinci et al., who showed that exogenous leptin therapy in adults with RLL reduced hepatic steatosis. Together, these findings support the idea of a metabolic phenotype characterized by relative leptin concentrations. The development of reference values for leptin concentrations according to sex, age, BMI or fat mass would allow more insights into these metabolic subtypes.

Reference: 1. Akinci, B.; Subauste, A.; Ajluni, N.; Esfandiari, N.H.; Meral, R.; Neidert, A.H.; Eraslan, A.; Hench, R.; Rus, D.; McKenna, B.; Hussain, H.K.; Chenevert, T.L.; Tayeh, M.K.; Rupani, a.R.; Innis, J.W.; Mantzoros, C.S.; Conjeevaram, H.S.; Burant, C.L.; Oral E.A. Metreleptin therapy for nonalcoholic steatohepatitis: Open-label therapy interventions in two different clinical settings? Med 2021, 9, 2(7):814-835. doi:10.1016/j.medj.2021.04.001.