Melanin‐concentrating hormone‐producing neurons in the hypothalamus regulate brown adipose tissue and thus contribute to energy expenditure

Key points Melanin‐concentrating hormone (MCH) neuron‐ablated mice exhibit increased energy expenditure and reduced fat weight. Increased brown adipose tissue (BAT) activity and locomotor activity‐independent energy expenditure contributed to body weight reduction in MCH neuron‐ablated mice. MCH neurons send inhibitory input to the medullary raphe nucleus to modulate BAT activity. Hypothalamic melanin‐concentrating hormone (MCH) peptide robustly affects energy homeostasis. However, it is unclear whether and how MCH‐producing neurons, which contain and release a variety of neuropeptides/transmitters, regulate energy expenditure in the central nervous system and peripheral tissues. We thus examined the regulation of energy expenditure by MCH neurons, focusing on interscapular brown adipose tissue (BAT) activity. MCH neuron‐ablated mice exhibited reduced body weight, increased oxygen consumption, and increased BAT activity, which improved locomotor activity‐independent energy expenditure. Trans‐neuronal retrograde tracing with the recombinant pseudorabies virus revealed that MCH neurons innervate BAT via the sympathetic premotor region in the medullary raphe nucleus (MRN). MRN neurons were activated by MCH neuron ablation. Therefore, endogenous MCH neuron activity negatively modulates energy expenditure via BAT inhibition. MRN neurons might receive inhibitory input from MCH neurons to suppress BAT activity.