University Hospital Zurich University of Zurich Fructose and sucrose but not glucosesweetened beverages promote hepatic de novo lipogenesis A randomized controlled trial J Hepatol 2021 Jul 7514654 ID: 1030459
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1. Bettina Geidl, PhDDivision of Endocrinology, Diabetes, and Clinical NutritionUniversity Hospital Zurich, University of ZurichFructose- and sucrose- but not glucose-sweetened beverages promote hepatic de novo lipogenesis: A randomized controlled trialJ Hepatol. 2021 Jul. 75(1):46-54
2. Sugar intake – a risk factor for metabolic disease NAFLDAdded SugarObesityJensen et al. Fructose and Sugar: A Major Mediator of Nonalcoholic Fatty Liver Disease. Jhepal, 2018
3. Glucose vs fructose metabolism3 GlucoseFructoseInsulinDe novo lipogenesisFructoseGlucoseGlycogen70%KHK-C
4. Aim of the study / hypotheses SucroseFructoseGlucoseFatty acid synthesisLipolysisInsulin resistance?β oxidationLipogenic enzymes?Muscle?Liver?Free fatty acid effluxFood intakeLaboratory parametersOGTTAdipokines80g/day
5. Study design: randomized controlled trialGlucoseNo SSB (Control)FructoseSucrose94 healthy young men, BMI < 24 kg/m2Week 5Week 7Week 0FFA oxidationLipolysisFatty acid and TAG synthesis/secretion LipolysisOGTTDietary intakeOGTTDietary intakeWeek 6
6. Hepatic de novo fatty acid synthesisG6PFructoseChREBPSREBP1cXBP-1Lipogenic genesFatty acid synthesisFatty acidsTAGGlucoseFatty acid oxidation genesPPARα Fatty acid oxidationBeta oxidation
7. Measurement of fatty acid synthesis by Mass Isotopomer Distribution Analysis (MIDA)TAGVLDL[2H5] glycerolPreformed FA[1,2-13C] acetateglucosePalmitate IsotopomersM+0, M+2, M+4 Palmitatede novo FA[2H5]glycerolglycerol3x Fatty acidTAG
8. Consumption of fructose- and sucrose-SSB increases basal FA synthesis
9. Lipolysis and FA oxidationTriglycerideLipolysisFatty acidsβ oxidationβ oxidation[2H5]glycerolU-13C-palmitate
10. Effects of SSB consumption on dietary intake*
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12. Effects of SSB on secondary outcome parametersSucroseFructoseGlucoseGlucose metabolismOral Glucose ToleranceFasting glucoseFasting insulinBlood lipidsFasting TAGFasting cholesterolAdipokinesLeptinGlucoseFructoseSucroseLDL profileSmall dense LDLGlucoseFructoseSucrose
13. Summary
14. Prof. Dr. Luc TappyPD Dr. Harald KöfelerDr. Isabelle Herter-AeberliDr. med. Agota NemethPD Dr. Michel HochuliProf. Dr. Kaspar Berneis † Prof. Dr. Giatgen SpinasPD Dr. Philipp GerberClinical Trial Center USZPhilhuman FoundationPromedica FoundationDr. Anita Eberl