High-fat and high-carbohydrate diets increase bone fragility through TGF-β-dependent control of osteocyte function.

ABSTRACT: Obesity can increase the risk of bone fragility, even when bone mass is intact. This fragility stems from poor bone quality, potentially caused by deficiencies in bone matrix material properties. However, cellular and molecular mechanisms leading to obesity-related bone fragility are not fully understood. Using male mouse models of obesity, we discovered TGF-β signaling plays a critical role in mediating the effects of obesity on bone. High-carbohydrate and high-fat diets increase TGF-β signaling in osteocytes, which impairs their mitochondrial function, increases cellular senescence, and compromises perilacunar/canalicular remodeling and bone quality. By specifically inhibiting TGF-β signaling in mouse osteocytes, some of the negative effects of high-fat and high-carbohydrate diets on bon

SUBMITTER: Dole NS 

PROVIDER: S-EPMC11343608 | biostudies-literature | 2024 Jul

REPOSITORIES: biostudies-literature