Mechanisms of lipotoxicity in bone

Abstract

Interest in the interaction between fat and bone has increased recently. Two types of fat and bone connection have been described in the literature: systemic and local. This thesis focuses on the local connection, which refers to the infiltration of fat within the bone marrow, and to those factors released by fat, such as fatty acids and adipokines, that could affect bone metabolism as well as the other surrounding bone cells. Previous studies have shown that when osteoblasts were cultured in the presence of adipocytes or fatty acids (palmitate and stearate), osteoblast function and survival were reduced. These fatty acids are abundant in bone marrow and have a toxic effect on the bone. This toxic effect is known as lipotoxicity. However, the mechanisms by which fatty acids and adipokines trigger lipotoxicity remain unclear. In order to investigate these molecular mechanisms, osteoblasts and osteocytes were treated with palmitic acid. In osteoblasts, palmitic acid affects osteoblastogenesis, cellular function and cell death, which is activated by two main death pathways, apoptosis and autophagy. In osteocytes, palmitic acid not only induces apoptosis, but failure of autophagy takes place. The present study, which focuses on fat-induced lipotoxicity in bone cells and the mechanism and inhibition of fat-induced lipotoxicity, may contribute to the identification of future therapeutic targets.