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The effect of fructose on intestinal triacylglycerol production and de novo fatty acid synthesis in humans and in an enterocyte model.

Steenson, Simon (2019) The effect of fructose on intestinal triacylglycerol production and de novo fatty acid synthesis in humans and in an enterocyte model. Doctoral thesis, University of Surrey.

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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.

Item Type: Thesis (Doctoral)
Divisions : Theses
Authors :
Steenson, Simon
Date : 28 February 2019
Funders : BBSRC DTP
DOI : 10.15126/thesis.00850160
Contributors :
Depositing User : Simon Steenson
Date Deposited : 25 Jan 2019 09:29
Last Modified : 15 Mar 2019 08:10

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