i DISRUPTION OF MITOCHONDRIAL FITNESS IN HUMAN PREADIPOCYTES BY FATTY ACIDS By

Adipose tissue lies at the core of energy metabolism, by not only releasing and taking up fatty acids (FA) according to the individuals energy requirements, but also signaling other tissues to regulate their own metabolism. If adipose tissue function is lost, insulin resistance, hypertriglyceridemia and hepatic steatosis can develop. Despite understanding how adipocytes function in normal and diseased states, preadipocytes, which can safeguard against adipocyte dysfunction by differentiating and joining the adipocyte pool, have been overlooked. Furthermore, how preadipocytes, which have a diminished capacity to esterify FA compared to adipocytes, are able to survive constant FA fluctuations within the adipose tissue depot without succumbing to lipotoxicity remains unclear. Therefore, how human preadipocytes sense and resist a mixture of FA (oleate, palmitate, stearate and linoleate) that resembles a healthy individual’s adipose tissue microenvironment was investigated. Experiments using a novel real-time flow cytometry device show that the maximal rate of mitochondrial superoxide accumulation, hydrogen peroxide (H2O2) production, and lipid ii peroxidation occurred within seconds of exposure to FA. Although mitochondrial ROS occurre