Arcuate nucleus of the hypothalamus cells are sensitive to nutritional state in a sex dependent manner.

Obesity has reached epidemic levels and obesity increases the risk for negative health outcomes including type 2 diabetes. Sex differences are evident in metabolic homeostasis with differences seen both in amount and location of adipose stores. Males store more adipose viscerally whereas females store adipose subcutaneously. Interestingly, this can be affected by the brain. The arcuate nucleus of the hypothalamus is a key brain region that exerts control over feeding behavior and metabolism. The cells of the arcuate are heterogeneous in their transcriptomic expression and in their functions. Here we perform single nuclei RNA-sequencing of the arcuate in females and males under varying nutritional states. We found that Agrp neurons were the most sensitive to nutritional state and this was more pronounced in females than in males. KNDy neurons were also sensitive to nutritional state and major sex differences were observed. Dopamine neurons of the arcuate had major sex differences. Ghrh neurons saw moderate nutritional regulation and sexual dimorphism. Both microglia and oligodendrocytes had moderate differences observed between nutritional states. This study represents the first major effort to characterize sex differences across nutritional states in the arcuate. Overall design: Female and male mice were either ad. Libitum fed or fasted for 28 hours, had their arcuate nucleus of the hypothalamus collected and processed for snRNA-seq.