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Firstly, we found that elevated expression of 11β-hydroxysteroid dehydrogenase type 1 (11β-HSD1), the key enzyme responsible for local glucocorticoid (GC) activation, was associated with high-fat diet (HFD)-induced bone loss and obesity. To elucidate the contribution of osteoblastic 11β-HSD1 in HFD-induced dysmetabolism, we established mice with targeted depletion of 11β-HSD1 in osteoblasts. We found that these mice were largely protected from HFD-induced bone loss, glucose intolerance, insulin resistance and obesity. Notably, they also exhibited increased bone formation and improved skeletal glucose uptake as compared to their wild-type littermates after HFD feeding. Mechanistically, we observed the aberrantly high osteoblastic 11β-HSD1 activated excessive GC to restrain the Egr2 (Early growth response protein 2)-governed osteogenic activity and glucose uptake. By using the osteoblast-specific 11β-HSD1 inhibitor in established HFD-fed obese mice models, we validated that targeted inhibition of 11β-HSD1 in osteoblasts not only markedly increased bone formation and enhanced intraosseous glucose uptake, but also attenuated bone loss, reduced weight gain and improved glucose metabolism in these mice. Therefore, targeting osteoblastic 11β-HSD1 emerges as a viable therapeutic avenue to counteract bone loss and metabolic disorders in obese individuals.