The role of dietary sugars and de novo lipogenesis in non-alcoholic fatty liver disease

J Bernadette Moore, Pippa J Gunn, Barbara A Fielding, J Bernadette Moore, Pippa J Gunn, Barbara A Fielding

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.

Figures

Figure 1
Figure 1
The effect of hypercaloric monosaccharide feeding on IHCL over seven days or less. * Values estimated from figures, T2D; type 2 diabetes, IHCL; intrahepatocellular lipid.
Figure 2
Figure 2
The effect of isocaloric (IC) and hypercaloric monosaccharide feeding on IHCL over more than seven days. (A) Changes in interventions using fructose and/or glucose. Interventions were hypercaloric unless otherwise stated (B) Changes in interventions using alternative fructose-containing solutions and comparators (Bravo et al. [104]; isocaloric high-fructose corn syrup (HFCS) vs. sucrose, Maersk et al. [103]; hypercaloric sucrose-sweetened beverage (SSB) vs. milk). * Values estimated from figures, IHCL; intrahepatocellular lipid.
Figure 3
Figure 3
The % of individual fatty acids (±SEM) that have arisen by DNL 4 h after healthy subjects consumed 0.75 g fructose/kg body weight (9% of energy requirement) as part of a mixed liquid meal. Calculated from data collected for Chong et al. [110].

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Source: PubMed

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