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Oxidative stress (OS) and mitochondrial dysfunction are key pathophysiological features of osteoporosis and obesity. Sodium butyrate (Na, produced by fermentation by the gut microbiota of the large intestine, has been demonstrated to protect against OS by improving specific antioxidant enzymes and to regulate mitochondria redox homeostasis in vivo. Here, in an unblinded study, we identified femur mitochondria as the main target of the beneficial effects of NaB, consisting of reversion of bone loss and body-weight gain in obesity-prone