Unloading-Induced Skeletal Interoception Alters Hypothalamic Signaling to Promote Bone Loss and Fat Metabolism.

ABSTRACT: Microgravity is the primary factor that affects human physiology in spaceflight, particularly bone loss and disturbances of the central nervous system. However, little is known about the cellular and molecular mechanisms of these effects. Here, it is reported that in mice hindlimb unloading stimulates expression of neuropeptide Y (NPY) and tyrosine hydroxylase (TH) in the hypothalamus, resulting in bone loss and altered fat metabolism. Enhanced expression of TH and NPY in the hypothalamus occurs downstream of a reduced prostaglandin E2 (PGE2)-mediated ascending interoceptive signaling of the skeletal interoception. Sympathetic antagonist propranolol or deletion of Adrb2 in osteocytes rescue bone loss in the unloading model. Moreover, depletion of TH⁺ sympathetic nerves or inhibi

SUBMITTER: Guo Q 

PROVIDER: S-EPMC10724445 | biostudies-literature | 2023 Dec

REPOSITORIES: biostudies-literature