title: The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease.
abstract: Dietary sugar consumption, in particular sugar-sweetened beverages and the monosaccharide fructose, has been linked to the incidence and severity of non-alcoholic fatty liver disease (NAFLD). Intervention studies in both animals and humans have shown large doses of fructose to be particularly lipogenic. While fructose does stimulate de novo lipogenesis (DNL), stable isotope tracer studies in humans demonstrate quantitatively that the lipogenic effect of fructose is not mediated exclusively by its provision of excess substrates for DNL. The deleterious metabolic effects of high fructose loads appear to be a consequence of altered transcriptional regulatory networks impacting intracellular macronutrient metabolism and altering signaling and inflammatory processes. Uric acid generated by fructose metabolism may also contribute to or exacerbate these effects. Here we review data from human and animal intervention and stable isotope tracer studies relevant to the role of dietary sugars on NAFLD development and progression, in the context of typical sugar consumption patterns and dietary recommendations worldwide. We conclude that the use of hypercaloric, supra-physiological doses in intervention trials has been a major confounding factor and whether or not dietary sugars, including fructose, at typically consumed population levels, effect hepatic lipogenesis and NAFLD pathogenesis in humans independently of excess energy remains unresolved.
authors.affiliation: Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK. j.b.moore@surrey.ac.uk.
authors.forename: J Bernadette
authors.initials: JB
authors.lastname: Moore
authors.affiliation: Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK. p.gunn@surrey.ac.uk.
authors.forename: Pippa J
authors.initials: PJ
authors.lastname: Gunn
authors.affiliation: Department of Nutritional Sciences, Faculty of Health and Medical Sciences, University of Surrey, Guildford, Surrey GU2 7XH, UK. B.Fielding@surrey.ac.uk.
authors.forename: Barbara A
authors.initials: BA
authors.lastname: Fielding
mesh_terms: D000818:Animals; D004040:Dietary Carbohydrates / Q000009:adverse effects* / Q000378:metabolism; D004734:Energy Metabolism / Q000235:genetics; D005247:Feeding Behavior; D005632:Fructose / Q000009:adverse effects* / Q000378:metabolism; D005786:Gene Expression Regulation; D006801:Humans; D050155:Lipogenesis / Q000235:genetics; D008099:Liver / Q000378:metabolism*; D065626:Non-alcoholic Fatty Liver Disease / Q000209:etiology* / Q000235:genetics / Q000378:metabolism; D009752:Nutritional Status; D018570:Risk Assessment; D012307:Risk Factors
chemical_list: D004040:Dietary Carbohydrates; D005632:Fructose