The response to prolonged fasting in hypothalamic serotonin transporter availability is blunted in obesity

Jan Booij,Katy A. van Galen,Ralph J. DiLeone,Gary J. Schwartz,Eric Fliers,Sofie M. Adriaanse,Unga A. Unmehopa,Kasper W. ter Horst,Anouk Schrantee,Mireille J. Serlie,Susanne E. la Fleur

doi:10.1016/j.metabol.2021.154839

Abstract

Background and aimsSerotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We therefore aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity. MethodsIn this randomized controlled cross-over trial, we assessed the effects of 12 vs 24 h of fasting on SERT and DAT availability in the hypothalamus/thalamus and striatum, respectively, using SPECT imaging in 10 lean men and 10 men with obesity. ResultsAs compared with the 12-h fast, a 24-h fast increased hypothalamic SERT availability in lean men, but not in men with obesity. We observed high inter-individual variation in the effects of fasting on thalamic SERT and striatal DAT, with no differences between lean men and those with obesity. In all subjects, fasting-induced increases in circulating free fatty acid (FFA) concentrations were associated with an increase in hypothalamic SERT availability and a decrease in striatal DAT availability. Multiple regression analysis showed that changes in plasma insulin and FFAs together accounted for 44% of the observed variation in striatal DAT availability. ConclusionLean men respond to prolonged fasting by increasing hypothalamic SERT availability, whereas this response is absent in men with obesity. Inter-individual differences in the adaptations of the cerebral serotonergic and dopaminergic systems to fasting may, in part, be explained by changes in peripheral metabolic signals of fasting, including FFAs and insulin.

Highlights

Obesity is defined as an excess of body fat and develops when longterm energy consumption exceeds energy expenditure [1]
There were no differences between groups in hypothalamic and thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability after the 12-h fast
Data from our study demonstrate that: i) a 24-h fast increases hypothalamic SERT availability in lean men, but not in men with obesity; ii) 24 h of fasting does not significantly affect mean thalamic SERT or striatal DAT availability in lean men nor in men with obesity, but with high inter-individual variation in the observed responses; and iii) fasting-induced changes in plasma free fatty acid (FFA) and insulin levels account for much of the observed variation

Summary

Introduction

Obesity is defined as an excess of body fat and develops when longterm energy consumption exceeds energy expenditure [1]. Serotonergic and dopaminergic systems in the brain are essential for homeostatic and reward-associated regulation of food intake and systemic energy metabolism. It is largely unknown how fasting influences these systems or if such effects are altered in humans with obesity. We aimed to evaluate the effects of fasting on hypothalamic/thalamic serotonin transporter (SERT) and striatal dopamine transporter (DAT) availability in lean subjects and subjects with obesity. We observed high inter-individual variation in the effects of fasting on thalamic SERT and striatal DAT, with no differences between lean men and those with obesity. Inter-individual differences in the adaptations of the cerebral serotonergic and dopaminergic systems to fasting may, in part, be explained by changes in peripheral metabolic signals of fasting, including FFAs and insulin

Methods

Results

Conclusion