Abstract
BackgroundLeptin and adiponectin communicate with organ systems in order to regulate energetic and metabolic homeostasis. Their different points of action have been well characterized; however, no study has investigated their interrelationship with the metabolism at the molecular level in vivo.ObjectiveTo examine the associations of leptin and adiponectin with the metabolic profile reflecting the intercellular and interorgan communication as well as activated metabolic pathways.Patients/MethodsWe measured plasma concentrations of leptin, adiponectin, and insulin along with concentrations of 196 metabolites in 400 healthy, fasting 8-years old German children who participated in the German Ulm Birth Cohort Study (UBCS). Using multiple linear mixed models, we evaluated the associations between hormones and metabolites.ResultsLeptin levels increased exponentially with increasing BMI. Leptin was furthermore strongly associated with alanine and aspartate (Bonferroni corrected P[PBF] = 5.7×10−8 and 1.7×10−6, respectively), and negatively associated to the sum of the non-esterified fatty acids (NEFA) and the sum of the long-chain acylcarnitines C12–C18 (PBF = 0.009 and 0.0001, respectively). Insulin showed a similar association pattern, although the associations were less strong than for leptin. Adiponectin was neither related to BMI nor to any metabolite.ConclusionAlthough children were presumably metabolically similar, we found strong associations of insulin and leptin with the metabolite profile. High alanine concentrations and the lower concentrations of NEFA in children with high fasting leptin concentrations might arise from an increased gluconeogenesis and from the disinhibiting effect of leptin on the carnitine-palmitoyltransferase-1, respectively. As insulin had the same trend towards these associations, both hormones seem to be related to processes that provide the body with energy in fasting state.
Highlights
While many mechanisms of action of the adipokines leptin and adiponectin, such as fatty acid oxidation enhancing the effect of leptin or the insulin sensitizing effect of adiponectin, have been elucidated, some other effects, like their role in glucose metabolism, are not yet fully understood because different studies reported controversial results [1, 2]
Children were presumably metabolically similar, we found strong associations of insulin and leptin with the metabolite profile
High alanine concentrations and the lower concentrations of Nonesterified acids (NEFA) in children with high fasting leptin concentrations might arise from an increased gluconeogenesis and from the disinhibiting effect of leptin on the carnitine-palmitoyltransferase-1, respectively
Summary
While many mechanisms of action of the adipokines leptin and adiponectin, such as fatty acid oxidation enhancing the effect of leptin or the insulin sensitizing effect of adiponectin, have been elucidated, some other effects, like their role in glucose metabolism, are not yet fully understood because different studies reported controversial results [1, 2]. Many of these studies are done on mice models and it remains to be clarified what these animal models reveal about humans [3]. Their different points of action have been well characterized; no study has investigated their interrelationship with the metabolism at the molecular level in vivo
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