Feeding Neurons Integrate Metabolic and Reproductive States in Mice

Abstract

Trade-offs between metabolic and reproductive processes are important for survival, particularly in mammals that gestate their young. Puberty and reproduction, as energetically taxing life stages, are often gated by metabolic availability in animals with ovaries. How the nervous system coordinates these trade-offs is an active area of study. We identify somatostatin neurons of the tuberal nucleus (TNSST) as a node of the feeding circuit that alters feeding in a manner sensitive to metabolic and reproductive states in mice. Whereas chemogenetic activation of TNSSTneurons increased food intake across sexes, selective ablation decreased food intake only in female mice during proestrus. Interestingly, this ablation effect was only apparent in animals with a low body mass. Fat transplantation and bioinformatics analysis of TNSSTneuronal transcriptomes revealed white adipose as a key modulator of the effects of TNSSTneurons on food intake. Together, these studies point to a mechanism whereby TNSSThypothalamic neurons modulate feeding by responding to varying levels of circulating estrogens differentially based on energy stores. This research provides insight into how neural circuits integrate reproductive and metabolic signals, and illustrates how gonadal steroid modulation of neuronal circuits can be context-dependent and gated by metabolic status.

Egr1 is a sex-specific regulator of neuronal chromatin, synaptic plasticity, and behaviour

“…The gene counts produced by Star were collated into a matrix. Differential gene expression analysis was then performed using DESeq2 10 at significance level p adj <0.05. Volcano plots were created using EnhancedVolcano (https://github.com/kevinblighe/EnhancedVolcano).…”

“…Sex-specific characteristics of the brain are dynamically shaped throughout life, as a result of the actions of gonadal hormones, sex chromosomes, and the environment 1,4 . During the reproductive period in females, cycling ovarian hormones, oestrogens and progesterone, play a critical role in brain plasticity relevant to reproductive and non-reproductive behaviours including mating, feeding 10,11 , learning 12,13 , reward processing 14,15 , and anxiety- and depression-related behaviours 6,7 . In addition, ovarian hormone shifts are associated with increased risk for neuropsychiatric conditions such as anxiety and depression disorders in women 7,16 .…”