Metabolic fate of fructose in human adipocytes: a targeted 13C tracer fate association study

Abstract

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.Electronic supplementary materialThe online version of this article (doi:10.1007/s11306-014-0716-0) contains supplementary material, which is available to authorized users.

Challenging metabolic tissues with fructose: tissue‐specific and sex‐specific responses

“…Their findings indicate that fructose is primarily used as an anabolic substrate, promoting the synthesis of new fatty acids and glutamate, rather than being oxidised (Varma et al . ). In keeping with this finding, greater adipogenic differentiation has been reported following administration of fructose, in combination with glucose, to human bone marrow‐derived mesenchymal stem cells (MSCs) and primary human white preadipocytes, compared to glucose treatment alone (Khitan et al .…”

“…To delineate the fructose effect and confirm these findings would require all cells to be exposed to the same total number of carbons from sugars. Furthermore, the presence of fructose appears to alter the fate of glucose (Varma et al 2015b). Fructose dose-dependently increased glucose oxidation to CO 2 in SGBS cells but not by an increased carbon flux through the TCA cycle.…”

“…Using the SGBS (Simpson–Golabi–Behmel syndrome, a congenital overgrowth syndrome) human preadipocyte cell line, Varma et al . (, b ) recently performed a series of detailed metabolic studies examining the influence of fructose on intermediary carbohydrate metabolism. Making use of stable isotope tracers, they were able to trace the fate of fructose within SGBS cells.…”

“…Furthermore, the presence of fructose appears to alter the fate of glucose (Varma et al . ). Fructose dose‐dependently increased glucose oxidation to CO 2 in SGBS cells but not by an increased carbon flux through the TCA cycle.…”

Vitamin A and its metabolic pathway play a determinant role in high‐fructose‐induced triglyceride accumulation of the visceral adipose depot of male Wistar rats

“…mediated fructose uptake, in the WAT 27,28. Further, a study ofRobubi et al 29 has demonstrated that preadipocyte treated with fructose has showed increased lipid vesicle formation by altering the mRNA expression of lipogenic pathway genes FAS and glycerol-3phosphate acyltransferase (GPAT) and GLUT5.…”