Dose Dependent Effects of Fructose and Glucose on de novo Palmitate and Glycerol Synthesis in an Enterocyte Cell Model

Abstract

Scope: Fructose exacerbates post-prandial hypertriacylglycerolaemia; perhaps partly due to increased enterocyte de novo lipogenesis (DNL). It is unknown whether this is concentration-dependent or if fructose has a greater effect on lipid synthesis than glucose. Dose-dependent effects of fructose and glucose on DNL and de novo triacylglycerol (TAG)-glycerol synthesis are investigated in a Caco-2 cell model. Methods and Results: Caco-2 cells are treated for 96 h with 5, 25, or 50 mM fructose or glucose, or 12.5 mM fructose/12.5 mM glucose mix. DNL is measured following addition of [13C2]-acetate to apical media. Separately, [13C6]-fructose and [13C6]-glucose are used to measure DNL and de novo TAG-glycerol synthesis. DNL from [13C2]-acetate is detected following all treatments, with greater amounts in intracellular than secreted (media) samples (all p < 0.05). DNL from [13C6]-fructose and [13C6]-glucose is also measurable. Intracellular synthesis is concentration-dependent for both glucose (p = 0.003) and fructose (p = 0.034) tracers and is higher with 25 mM glucose than 25 mM fructose (p = 0.025). DNL from fructose and glucose is <1%, but up to 70% of de novo TAG-glycerol is synthesized from glucose or fructose. Conclusion: Fructose is not a major source of DNL in Caco-2 cells but contributes substantially to de novo TAG-glycerol synthesis.