Deciphering the Role of SYNGAP1 in the Adipose Tissue

Abstract

Obesity has been regarded throughout history as a consequence of overeating; however, over the past two decades, research has revealed the involvement of complex networks and pathways that regulate feeding behaviour and energy expenditure. Among these, the crosstalk between the brain and adipose tissue plays a crucial role in maintaining energy homeostasis. Recent studies have discovered that secretions from adipose tissue can influence neuronal structure and synaptic plasticity. This study aims to investigate whether the reverse interaction, namely the influence of neuronal factors on adipose tissue, also occurs. SYNGAP1 is a postsynaptic protein involved in neuronal plasticity and has been reported to be hypomethylated in cases of obesity. To address this, in this study, the thermogenic and mitochondrial functions of adipose tissue were examined in mice with Syngap1 haploinsufficiency under basal and β3- adrenergic stimulated conditions. The Syngap1 haploinsufficiency resulted in minimal changes in brown adipose tissue; however, a unique and enhanced thermogenic and mitochondrial response was observed in inguinal white adipose tissue under experimental conditions. These findings indicate that alterations in the neuronal synaptic proteins may have an effect on adipose tissue function indirectly through neural pathways, highlighting a novel dimension of the brain-adipose tissue crosstalk in the regulation of energy homeostasis.