Skeleton interoception regulates bone and fat metabolism through hypothalamic neuroendocrine NPY.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 34468315.
- Also identified by DOI 10.7554/eLife.70324 and PMC identifier 8439655.
- Licence recorded as CC BY.
- The licence permits redistribution, so the abstract is shown in full and the full text is available from the publisher.
Abstract
The central nervous system regulates activity of peripheral organs through interoception. In our previous study, we have demonstrated that PGE2/EP4 skeleton interception regulate bone homeostasis. Here, we show that ascending skeleton interoceptive signaling downregulates expression of hypothalamic neuropeptide Y (NPY) and induce lipolysis of adipose tissue for osteoblastic bone formation. Specifically, the ascending skeleton interoceptive signaling induces expression of small heterodimer partner-interacting leucine zipper protein (SMILE) in the hypothalamus. SMILE binds to pCREB as a transcriptional heterodimer on <i>Npy</i> promoters to inhibit NPY expression. Knockout of EP4 in sensory nerve increases expression of NPY causing bone catabolism and fat anabolism. Importantly, inhibition of NPY Y1 receptor (Y1R) accelerated oxidation of free fatty acids in osteoblasts and rescued bone loss in <i>Avil<sup>Cre</sup>:Ptger4<sup>fl/fl</sup></i> mice. Thus, downregulation of hypothalamic NPY expression lipolyzes free fatty acids for anabolic bone formation through a neuroendocrine descending interoceptive regulation.
Medical subject headings
- Adipose Tissue
- Bone and Bones
- Hypothalamus
- Interoception
- Neuropeptide Y
- Skeleton