Research ArticleHigh-fructose corn syrup-55 consumption alters hepatic lipid metabolism and promotes triglyceride accumulation☆
Introduction
Fructose consumption has dramatically increased in recent decades in the United States with the major source being from soft drink intake [1]. This has significant health implications since high dietary fructose intake has been reported to promote hepatic de novo lipogenesis (DNL), which increases the risk of adiposity and metabolic disorders [2], [3], [4]. High-fructose corn syrup-55 (HFCS-55) and sucrose are the major caloric sweeteners added to beverages and soft drinks [5]. Sucrose consists of 50% fructose and 50% glucose compared to HFCS-55, which consists of 55% fructose and 45% glucose [6]. Whether this slightly higher fructose content can contribute to greater risk of metabolic disorders and weight gain is unclear.
High carbohydrate intake stimulates the expression of transcription factors including sterol regulatory element-binding protein-1c (SREBP-1c) and carbohydrate response element binding protein (ChREBP) that induces the expression of genes involved in DNL [7]. Palmitic acid (16:0) is the final product of the series of reactions catalyzed by fatty acid synthase (FAS). In turn, palmitic acid can be elongated to other saturated fatty acids (SFAs). Stearoyl-CoA desaturase-1 (SCD-1) catalyzes the conversion of SFA into monounsaturated fatty acids (MUFAs). Burhans et al. [8] reported an inverse relationship between tissue MUFA content and metabolic health. Basaranoglu et al. [9] suggested that HFCS-containing beverages are associated with the development of nonalcoholic fatty liver disease (NAFLD) through increased hepatic DNL.
Other changes in lipid metabolism that may contribute to NAFLD include increased adipose lipolysis, decreased lipid export and reduced fatty acid oxidation [10]. Peroxisome proliferator–activated receptor α (PPARα) is a transcription factor that regulates the expression of genes involved in hepatic fatty acid oxidation [11]. Studies reported down-regulation of PPARα gene expression resulted in increased hepatic triglyceride accumulation [12]. NAFLD, characterized by hepatic triglyceride accumulation, has been diagnosed worldwide and is the most common liver disorder in Western countries [13]. High dietary fructose intake has been shown to promote NAFLD and related metabolic disorders [14]. However, few studies have investigated whether the slightly higher fructose content of HFCS-55 compared to sucrose at doses found in soft drinks is more lipogenic [9]. Therefore, the objectives of this study were to determine the effect of HFCS-55-sweetened solution intake on hepatic gene expression of lipid metabolism in relation to liver fatty acid composition and NAFLD risk using a rat model.
Section snippets
Animals and diets
Female rats were used due to their greater susceptibility to hepatic effects with fructose consumption than male rats [15]. Weanling female Sprague–Dawley rats (n=28) were purchased from Taconic Farms (Rockville, MD). All animal procedures were approved by the Animal Care and Use Committee at West Virginia University and conducted in accordance with the guidelines of the National Research Council for the Care and Use of Laboratory Animals [16]. Following a 7-day acclimation, rats were randomly
Caloric, sugar and fat intake
Shown in Table 1, rats drinking HFCS-55 or sucrose solutions had higher (P=.01) total liquid intake compared to rats drinking fructose solution and water. All rats drinking sugar solutions had significantly lower total food intake as purified AIN-93G diet and fat intake compared to rats drinking water. Standard purified AIN-93G diet consists of energy 3.8 kcal/g, 70 g/kg soybean oil and 10 g/kg sucrose. Ad libitum intake of sugar from beverage and food resulted in higher (P=.02) total sugar
Discussion
Drinking 13% (w/v) HFCS-55 solution resulted in the highest (P=.03) hepatic total lipid and triglyceride content. Histological evaluation also indicated rats drinking HFCS-55 solution had the most extensive hepatic lipid infiltration. Hepatic lipid accumulation was the result of an imbalance resulting from increased inflow from adipose lipolysis promoting DNL and reduced lipid disposal due to decreased β-oxidation without an increase in outflow of triglyceride-rich lipoproteins. This is of
Acknowledgments
We thank Stephanie Altman for assisting with the fatty acid analysis and Susan Slider for running the fatty acid samples.
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Conflict of Interest: The authors declare that they have no competing interests. Funding for this project was provided in part by the West Virginia University Program to Stimulate Competitive Research and Agricultural, Forestry Experimental Station Hatch Grant H45 and Summer Undergraduate Research Education program.