Direct impact of fructose on hepatic lipid and glycogen metabolism

Background Overconsumption of fructose has been identified as major risk factor for the development of non-alcoholic fatty liver disease (NAFLD). Although the impact of dietary fructose on NAFLD development is multifactorial, a fructose-dependent increase in hepatic de novo fatty acid synthesis with an ensuing intrahepatic triglyceride accumulation is frequently claimed to be a relevant mechanism. However, direct evidence for such a mechanism is largely lacking.

Methods Rat hepatocyte cultures were incubated with varying concentrations of glucose and fructose ± insulin and the incorporation of a [14C]-label from glucose and fructose into glycogen and lipids was quantified.

Results [14C]-label from glucose and fructose was incorporated into glycogen. This incorporation was stimulated five to ten-fold by insulin. At low (5 mM) glucose concentrations and in absence of insulin, fructose (2 mM) enhanced the incorporation of [14C]-glucose into glycogen. This effect was no longer observed at high (20 mM) glucose concentrations or in presence of insulin.

Both [14C]-glucose and [14C]-fructose were incorporated into hepatic lipids. The incorporation was stimulated three to four-fold by insulin. Neither monosaccharide affected the incorporation of the other. Notably, however, both in absence and presence of insulin, the [14C]-hexose incorporation into lipids from a mixture of 2 mM fructose and 5 mM glucose was higher than from 7 mM Glucose. This effect of fructose was no longer observed at higher glucose concentrations.

Conclusion Thus, only at low physiological glucose concentrations but not at high postprandial glucose concentrations, fructose might directly drive lipid incorporation into hepatocytes.

Publikationsverlauf

Artikel online veröffentlicht:
26. Januar 2022