Consumption of high-fructose corn syrup compared with sucrose promotes adiposity and increased triglyceridemia but comparable NAFLD severity in juvenile Iberian pigs

Authors: MAJ, MAGDALENA - California Polytechnic State University; HARBOTTLE, BROOKE - California Polytechnic State University; THOMAS, PAYTON - California Polytechnic State University; HERNANDEZ, GABRIELLA - California Polytechnic State University; SMITH, VICTORIA - California Polytechnic State University; EDWARDS, MARK - California Polytechnic State University; FANTER, ROB - California Polytechnic State University; GLANZ, HUNTER - California Polytechnic State University; IMMOOS, CHAD - California Polytechnic State University; Burrin, Douglas - Doug; SANTIAGO-RODRIGUEZ, TASHA - Divergence, Inc; LA FRANCO, MICHAEL - California Polytechnic State University; MANJARIN, RODRIGO - California Polytechnic State University

Submitted to: Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/16/2020
Publication Date: 3/9/2021
Citation: Maj, M., Harbottle, B., Thomas, P., Hernandez, G., Smith, V., Edwards, M., Fanter, R., Glanz, H., Immoos, C., Burrin, D.G., Santiago-Rodriguez, T., La Franco, M., Manjarin, R. 2021. Consumption of high-fructose corn syrup compared with sucrose promotes adiposity and increased triglyceridemia but comparable NAFLD severity in juvenile Iberian pigs . Journal of Nutrition. 151(5):1139-1149. https://doi.org/10.1093/jn/nxaa441.
DOI: https://doi.org/10.1093/jn/nxaa441

Interpretive Summary: Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the U.S. The cause of NAFLD in children has been linked to excessive consumption of a nutrient rich diet, but it is not clear how specific nutrients lead to liver disease. There is increasing concern about the consumption of high fructose corn syrup and its potential contribution to NAFLD in children. In this study, we used our new model of pediatric NAFLD using a strain of Iberian pigs to test whether different types of sugar in a high calorie but low fat diet influences the development of the disease in infant pigs. The aim of this study was to test whether high fructose corn syrup compared to sucrose influence the signs of NAFLD after 16 weeks. We found that compared to a control low calorie diet, pigs fed a high calorie high sugar diet developed signs of obesity, namely increased subcutaneous fat and less muscle mass. However, there were few substantial differences in markers of NAFLD between HFCS and sucrose diet fed pigs. These findings in juvenile pigs would imply that consuming a high sugar diet leads to adverse metabolic outcomes regardless of the type of sugar consumed.

Technical Abstract: Fructose consumption has been linked to non-alcoholic fatty liver disease (NAFLD) in children. However, the effect of high-fructose corn syrup (HFCS) vs. sucrose in pediatric NAFLD has not been investigated. We tested whether the isocaloric substitution of dietary sucrose by HFCS would increase the severity of NAFLD in juvenile pigs, and whether this effect would be associated with changes in gut histology, short-chain fatty acid (SCFA) production and microbial diversity. 53-d-old Iberian pigs pair-housed in pens balanced for weight and sex were randomly assigned to receive a mesh diet top-dressed with sucrose (SUC; n = 3 pens; 281.6 to 486.8 g/kg-1 diet) or HFCS (n = 4; 444.3 to 724.8 g/kg-1 diet) for 16 weeks. Diets exceeded the animal's energy requirements by providing sugars in excess, but met the requirements for all other nutrients. Animals were euthanized at 165 d of age after blood sampling, and liver and gut were collected for histology, metabolome, and microbiome analyses. Data was analyzed by multivariate and univariate statistics. Compared with SUC, HFCS increased backfat thickness over the loin, triacylglyceride in plasma and butyrate in colon (P = 0.05). In addition, HFCS decreased uridine monophosphate and short-chain acyl carnitines in liver, and urea nitrogen and creatinine in serum (P = 0.05). Multivariate analysis showed a 24.8% average dissimilarity between HFCS and SUC microbiomes, associated with changes in SCFA producing-bacteria. Body weight gain, histological and serum markers of liver injury, and circulating hormones, glucose, and pro-inflammatory cytokines did not differ between diets. Fructose consumption derived from HFCS promoted butyrate synthesis and subcutaneous lipid deposition in juvenile Iberian pigs, but did not increase serum and histological markers of NAFLD compared with a sucrose-enriched diet. Longer studies may be needed to observe differences in liver injury among sugar types.