Orexin neuropeptides promote arousal, appetite, reward, and energy expenditure. However, whether orexin affects bone mass accrual is unknown. Here, we show that orexin functions centrally through orexin receptor 2 (OX2R) in the brain to enhance bone formation. OX2R null mice exhibit low bone mass owing to elevated circulating leptin, whereas central administration of an OX2R-selective agonist augments bone mass. Conversely, orexin also functions peripherally through orexin receptor 1 (OX1R) in the bone to suppress bone formation. OX1R null mice exhibit high bone mass owing to a differentiation shift from marrow adipocyte to osteoblast that results from higher osseous ghrelin expression. The central action is dominant because bone mass is reduced in orexin null and OX1R2R double null mice but enhanced in orexin-overexpressing transgenic mice. These findings reveal orexin as a critical rheostat of skeletal homeostasis that exerts a yin-yang dual regulation and highlight orexin as a therapeutic target for osteoporosis.
Pharmacology, Toxicology and Pharmaceutical Science
2
4%
Other
6
11%
Unknown
13
23%
Attention Score in Context
Attention Score in Context
This research output has an Altmetric Attention Score of 33. This is our high-level measure of the quality and quantity of online attention that it has received. This Attention Score, as well as the ranking and number of research outputs shown below, was calculated when the research output was last mentioned on 14 July 2026.
All research outputs
#1,557,365
of 34,601,305 outputs
Outputs from Cell Metabolism (Science Direct)
#1,365
of 3,818 outputs
Outputs of similar age
#12,588
of 276,191 outputs
Outputs of similar age from Cell Metabolism (Science Direct)
#14
of 59 outputs
Altmetric has tracked 34,601,305 research outputs across all sources so far. Compared to these this one has done particularly well and is in the 95th percentile: it's in the top 5% of all research outputs ever tracked by Altmetric.
So far Altmetric has tracked 3,818 research outputs from this source. They typically receive a lot more attention than average, with a mean Attention Score of 75.9. This one has gotten more attention than average, scoring higher than 64% of its peers.
Older research outputs will score higher simply because they've had more time to accumulate mentions. To account for age we can compare this Altmetric Attention Score to the 276,191 tracked outputs that were published within six weeks on either side of this one in any source. This one has done particularly well, scoring higher than 95% of its contemporaries.
We're also able to compare this research output to 59 others from the same source and published within six weeks on either side of this one. This one has done well, scoring higher than 76% of its contemporaries.
