Effect of chronic restraint stress or repeated activation of PVN neurons responding to restraint stress on gene expression of white adipose tissues (iWAT and eWAT) during adipogenesis of mice

Comorbid depression and type 2 diabetes (T2D) is associated with more severe symptoms, higher suicide risk and poorer prognosis than those with either disease alone. However, the mechanisms underlying this comorbidity remain unclear. Here, we describe a brain–sympathetic nerve–adipose circuit originating in the hypothalamic paraventricular nucleus (PVN) that is crucial for the depressive-like behaviours and insulin resistance induced by chronic restraint stress. A subset of PVN neurons that were traced from WAT and activated under restraint stress, and chemogenetic manipulations demonstrated the sufficiency and necessity of those PVN neurons for changes in sympathetic innervation of adipose tissue and subsequent depression and insulin resistance induced by chronic stress. We further identify candidate adipokines for the development of depression and insulin resistance, and clarify the molecular mechanism by which the dynamics of sympathetic tone are translated into changes in the expression of candidate adipokines. Overall design: Adipose tissue (iWAT and eWAT) mRNA profiles of control group mice and the restraint group mice as well as mcherry group mice and hM3D group mice