This study investigated the effects of high-fat diet (HFD) and obesity on bone loss in mice. Researchers found that HFD-induced obesity, but not HFD alone, led to bone loss. Non-obese mice fed an HFD maintained healthy bones due to a gut microbiome that promoted short-chain fatty acid (SCFA) production. These SCFAs activated free fatty acid receptor 2 (FFAR2) and inhibited histone deacetylases, leading to increased Treg cell proliferation and inhibition of osteoclastogenesis. Fecal microbiota transplantation from non-obese mice to obese mice reversed bone loss, highlighting the importance of the gut microbiome in bone health.
