Alk-Fam150b (augmentor α) expression in the paraventricular nucleus of the mouse hypothalamus at molecular resolution, and its sensitivity to acute stress.

Augmentor α (Fam150b)-induced activation of the ALK receptor (Alk) has gained significance as a hypothalamic signaling pathway with relevance to the control of food intake and energy homeostasis. In contrast, much less is known about the sensitivity of Fam150b-Alk expression and signaling upon noxious challenges. In this regard, acute stress is of particular interest because augmentor α, released from afferents of the food intake circuit of the arcuate nucleus within the paraventricular hypothalamus (PVN), could link stress-induced changes in food consumption. Nevertheless, conflicting data exist on whether Fam150b mRNA is expressed in the PVN. Here, we combined single-cell RNA-seq and multiplexed in situ hybridization to demonstrate that both Fam150b and Alk are expressed in the PVN of adult mice, including corticotropin-releasing hormone (CRH)-containing neurons. As such, a dichotomy of CRH neurons is present through their mutually exclusive expression of either Fam150b or Scgn (secretagogin). Fam150b and Alk were not co-expressed. When inducing inflammation-associated stress, Fam150b but not Alk mRNA expression increased in a mifepristone-sensitive manner, implying regulation by peripheral glucocorticoid feedback. We suggest that augmentor α-ALK signaling could underpin, at least partly, stress-induced changes in feeding and the control of body weight.