Förderung 2016

"Bone metabolism and Lipotoxicity in Obesity"

Summary:

This application addresses the mechanisms underlying bone loss in obesity. We will analyze fundamental molecular pathways regulating bone homeostasis in obesity and define how these are modulated in response to periodontal bacterial infection.

The central hypothesis of the application is that excessive accumulation of saturated palmitic acid (PA) and downstream lipotoxic metabolic intermediates impact bone metabolism and modulates how bone responds to periodontal bacterial infection in obesity. Aim 1 will systematically analyze how saturated PA impacts bone structure and remodeling. We will define which lipid metabolites accumulate in bone and surrounding tissue to identify potential molecular pathways that drive bone loss in obesity. In Aim 2, we will evaluate how osteoblast and osteoclast cellular interactions are influenced by elevated fatty acids (FA). Aim 3 will investigate molecular mechanisms regulating local alveolar bone loss in periodontal infections to determine the impact of inflammatory changes on bone catabolism in obesity. Further, we will test whether pharmacologic inhibition of ceramide metabolism reducing lipotoxicity affects periodontal bone loss in obese animals on a high fat PA diet. In summary, our studies will broaden the understanding of the growing obesity epidemic and test novel therapeutic strategies that may ultimately lead to the identification of targets for new innovative therapeutic interventions counteracting bone loss.