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

• Published in: Nutrients Vol. 15; no. 1; p. 19
• Main Authors: Shi, Zunhan, Wang, Lihui, Luan, Jinwen, Yin, Liqin, Ji, Xiaohui, Zhang, Wenqian, Xu, Bingxiang, Chen, Linshan, He, Ying, Wang, Ru, Liu, Longhua
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 21.12.2022; MDPI
• Subjects: Adipose tissue; Adipose tissues; adipsin; alternative complement pathway; Body fat; Bone density; Bone loss; Bone marrow; Bone remodeling; Bone resorption; Bones; Cancellous bone; Cardiovascular diseases; Care and treatment; China; Complement activation; Complications and side effects; Density; Diabetes; Diabetes mellitus; Diet; Epidemics; Exercise; Glucose; Health aspects; Homeostasis; Insulin; Males; Mesenchyme; Metabolism; Microenvironments; Musculoskeletal diseases; Obesity; Osteoclastogenesis; Osteoclasts; Osteoporosis; Physiological aspects; Prevention; Proteins; Risk factors; RNA; RNA sequencing; Sample size; Signal transduction; Stem cell transplantation; Stem cells; China; exercise; adipsin; obesity; alternative complement pathway; bone resorption
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu15010019

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.