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Title: The effect of fructose on intestinal triacylglycerol production and de novo fatty acid synthesis in humans and in an enterocyte model
Author: Steenson, Simon
ISNI:       0000 0004 7657 4019
Awarding Body: University of Surrey
Current Institution: University of Surrey
Date of Award: 2019
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Background: Cardiovascular disease (CVD) remains a significant cause of mortality globally, with a reduction in free sugars consumption a public health target for decreasing disease burden. Fructose raises post-prandial triacylglycerol (TAG) concentrations (risk factor for CVD), relative to glucose or sucrose, possibly due disrupted intestinal TAG metabolism. Aims: Determine whether effects of high-fructose consumption on plasma TAG concentration are explained by intestinal and/or hepatic TAG lipoprotein kinetics, as well as de novo lipogenesis (DNL), in humans and an in vitro model. Methods: Five overweight males consumed drinks containing 30% energy as fructose or complex carbohydrate hourly for 11h on two separate occasions, in a randomised cross-over design (4 week washout). Stable isotopes were given to measure DNL, chylomicron (CM)-TAG and VLDL-TAG kinetics. CM and VLDL were separated according to their apolipoprotein B (apoB) content (Sf > 20 fraction). Caco-2 cells were treated (96h) with different fructose and glucose concentrations, or a mixture of sugars ("Mix"), and stable isotopes tracers ([13C6]-fructose; [13C6]-glucose). TAG enrichments were measured by gas chromatography-mass spectrometry. Results: Fructose consumption in comparison to the complex CHO had no effect on either intestinal or hepatic DNL. Intestinal and hepatic DNL were correlated in the fasted (P < 0.0001) and fed state (P≤0.004). Plasma TAG (P < 0.005) and VLDL-TAG (P=0.003) were greater, and CM-TAG production rate (PR, P=0.046) and fractional catabolic rate (FCR, P=0.073) lower, when fructose was consumed, with no differences in VLDL-TAG kinetics. Insulin was lower (P=0.005) and apoB48 (P=0.039), apoB100 (P=0.013) and plasma NEFA (P=0.013) higher in response to fructose. Caco-2 cells utilised fructose and glucose for TAG-palmitate and TAG-glycerol synthesis dose-dependently, with more palmitate derived from glucose after "Mix" treatment (P < 0.05). Conclusions: Fructose increased post-prandial TAG concentrations, possibly due to less insulin-mediated lipoprotein metabolism. DNL was unaffected by fructose consumption. This study supports public strategies to restrict dietary free sugars.
Supervisor: Umpleby, Margot Sponsor: BBSRC
Qualification Name: Thesis (Ph.D.) Qualification Level: Doctoral