Diacylglycerol ameliorates obesity-induced osteoporosis through inhibiting NF-κB pathway mediated osteoclast differentiation

With the rapid increase in obesity rates, osteoporosis caused by obesity has become a serious social health problem. Diacylglycerol (DAG) is a structural lipid with multiple metabolism benefits. However, the effects and underlying mechanisms of DAG in bone health are still unclear. In this study, an obese osteoporosis mouse model was supplemented with DAG for 12 weeks. Results showed that DAG supplementation significantly attenuated HFD-induced weight gain and improved the bone mineral density, biomechanical strength, and trabecular microarchitecture. Lipidomics and transcriptomics revealed that DAG supplementation reshaped the lipid composition, targeted the NF-κB signaling cascade, and downregulated the expression of osteoclastogenic factors (RANKL, NFATC1, and c-Fos), thereby inhibiting osteoclast differentiation and promoting osteogenic differentiation. These findings demonstrated that DAG ameliorated obesity-induced osteoporosis by modulating lipid metabolism and inhibiting the NF-κB pathway, highlighting its potential as a functional food ingredient for improving both health.