The development of obesity is becoming an international problem and the role of fructose is unclear. Studies using liver tissue and hepatocytes have contributed to the understanding of fructose metabolism. Excess fructose consumption also affects extra hepatic tissues including adipose tissue. The effects of fructose on human adipocytes are not yet fully characterized, although in vivo studies have noted increased adiposity and weight gain in response to fructose sweetened-beverages. In order to understand and predict the metabolic responses of adipocytes to fructose, this study examined differentiating and differentiated human adipocytes in culture, exposed to a range of fructose concentrations equivalent to that reported in blood after consuming fructose. A stable isotope based dynamic profiling method using [U-13C6]-d-fructose tracer was used to examine the metabolism and fate of fructose. A targeted stable isotope tracer fate association method was used to analyze metabolic fluxes and flux surrogates with exposure to escalating fructose concentration. This study demonstrated that fructose stimulates anabolic processes in adipocytes robustly, including glutamate and de novo fatty acid synthesis. Furthermore, fructose also augments the release of free palmitate from fully differentiated adipocytes. These results imply that in the presence of fructose, the metabolic response of adipocytes in culture is altered in a dose dependent manner, particularly favoring increased glutamate and fatty acid synthesis and release, warranting further in vivo studies.
Keywords: 13C labeled fructose; Fatty acids; Fructose metabolism; Human adipocytes; Isobolomics; Targeted tracer fate association study.