Abstract
This study investigates the relationship between ambient temperature, brown adipose tissue (BAT) function, and bone metabolism, revealing how cold exposure and BAT mitochondrial activity influence bone health. Utilizing ovariectomized (OVX) mice to model primary osteoporosis and BAT-specific mitochondrial dysfunction (BKO) mice, we explored the effects of housing temperature on bone density, immune modulation in bone marrow, and the protective role of BAT against bone loss. The results showed that cold exposure universally decreases bone mass, increases osteoclastogenesis, and shifts bone marrow T-cell populations, suggesting a key role of the immune system in bone remodeling under cold stress. Crucially, the thermogenic function of BAT, underpinned by mitochondrial oxidative phosphorylation, protected against bone loss. Impairments in BAT function, either through surgical removal or mitochondrial dysfunction, exacerbated bone loss in cold environments, highlighting the importance of BAT metabolic activity for bone health. Additionally, we found that cold-induced alterations in BAT function led to systemic metabolic changes, including increased long-chain fatty acid levels, which directly and indirectly affected osteoclast differentiation and activity. These findings point to a systemic mechanism via which environmental temperature and BAT metabolism are interconnected with bone physiology, offering new insights into the metabolic and environmental determinants of bone health. In summary, our study underscores the complex interactions between ambient temperature, BAT function, and bone health, suggesting that novel bone disease therapies could be developed by targeting metabolic and environmental factors. Further research in these pathways may provide innovative approaches for managing bone health amid changing environmental conditions and metabolic dysfunctions.