Exercise Promotes Bone Marrow Microenvironment by Inhibiting Adipsin in Diet-Induced Male Obese Mice

Obesity is a growing global epidemic linked to many diseases, including diabetes, cardiovascular diseases, and musculoskeletal disorders. Exercise can improve bone density and decrease excess bone marrow adipose tissue (BMAT) in obese individuals. However, the mechanism of exercise regulating bone marrow microenvironment remains unclear. This study examines how exercise induces bone marrow remodeling in diet-induced obesity. We employed unbiased RNA-Seq to investigate the effect of exercise on the bone marrow of diet-induced obese male mice. Bone mesenchymal stem cells (BMSCs) were isolated to explore the regulatory effects of exercise in vitro. Our data demonstrated that exercise could slow down the progression of obesity and improve trabecular bone density. RNA-seq data revealed that exercise inhibited secreted phosphoprotein 1 (Spp1), which was shown to mediate bone resorption through mechanosensing mechanisms. Interactome analysis of Spp1 using the HINT database showed that Spp1 interacted with the adipokine adipsin. Moreover, exercise decreased BMAT, which induced osteoclast differentiation and promoted bone loss. Our study reveals that exercise improves the bone marrow microenvironment by at least partially inhibiting the adipsin-Spp1 signaling pathway so as to inhibit the alternative complement system from activating osteoclasts in diet-induced obese mice.

Automated summary

Obesity is a global epidemic associated with various diseases, and exercise has been shown to improve bone density and decrease excess bone marrow adipose tissue. This study investigated the mechanism by which exercise remodels the bone marrow microenvironment in diet-induced obese mice. The data revealed that exercise could slow down obesity progression, improve trabecular bone density, and inhibit the adipsin-Spp1 signaling pathway, thereby preventing the activation of osteoclasts in obese mice.