High-fructose, high-fat diet alters muscle composition and fuel utilization in a juvenile iberian pig model of non-alcoholic fatty liver disease

Authors: SPOONER, HEATHER - California Polytechnic State University; DERRICK, STEFANI - California Polytechnic State University; MAJ, MAGDALENA - California Polytechnic State University; MANJARIN, RODRIGO - California Polytechnic State University; HERNANDEZ, GABRIELLA - California Polytechnic State University; TAILOR, DEEPALI - California Polytechnic State University; BASTANI, PARISA - California Polytechnic State University; FANTER, ROB - California Polytechnic State University; FIOROTTO, MARTHA - Children'S Nutrition Research Center (CNRC); Burrin, Douglas - Doug; LAFRANO, MICHAEL - California Polytechnic State University; SIKALIDIS, ANGELOS - California Polytechnic State University; BLANK, JASON - (NCE, CECR)networks Of Centres Of Exellence Of Canada, Centres Of Excellence For Commercilization A

Submitted to: Nutrients
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 11/21/2021
Publication Date: 11/23/2021
Citation: Spooner, H., Derrick, S., Maj, M., Manjarin, R., Hernandez, G., Tailor, D., Bastani, P., Fanter, R., Fiorotto, M., Burrin, D.G., LaFrano, M., Sikalidis, A., Blank, J. 2021. High-fructose, high-fat diet alters muscle composition and fuel utilization in a juvenile Iberian pig model of non-alcoholic fatty liver disease. Nutrients. 13(12). Article 4195. https://doi.org/10.3390/nu13124195.
DOI: https://doi.org/10.3390/nu13124195

Interpretive Summary: In the U.S. there has been a marked increase in the number of children that develop fatty liver disease, also called NAFLD. This disease is often linked to increased consumption of foods high in fat and sugar. We previously reported results from a study using a unique breed of Iberian pigs that develop NAFLD after only three months of age when fed a diet high in fat and sugar. This pig breed provides a new animal model to explore how pediatric NAFLD influences development in children. In this study, we examined whether there were adverse effects of feeding a diet high in fat and sugar on skeletal muscle fiber composition as studies in adults with NAFLD suggest a loss of muscle function. The main aim of the current study was to test whether young pigs fed a high fat diet would is associated with changes in muscle phenotype that might affect fuel utilization and storage despite the absence of obesity and insulin resistance, potentially linking a "Western-style diet" to changes in muscle quality and functionality. Our results showed that pigs fed the high fat-sugar diet for 3 months had more fat in the muscle tissue but less inside muscle fiber cells themselves. Pigs with NAFLD also showed an accumulation of fat metabolites suggest a reduction in the type of muscle cells that metabolize fat. This study in a new pig model of pediatric NAFLD shows that reductions in metabolically active muscle cells may explain why high fat diets might lead to deterioration of muscle function in children.

Technical Abstract: Non-alcoholic fatty liver disease (NAFLD) is a serious metabolic condition affecting millions of people worldwide. A "Western-style diet" has been shown to induce pediatric NAFLD with the potential disruption of skeletal muscle composition and metabolism. To determine the in vivo effect of a "Western-style diet" on pediatric skeletal muscle fiber type and fuel utilization, 28 juvenile Iberian pigs were fed either a control diet (CON) or a high-fructose, high-fat diet (HFF), with or without probiotic supplementation, for 10 weeks. The HFF diets increased the total triacylglycerol content of muscle tissue but decreased intramyocellular lipid (IMCL) content and the number of type I (slow oxidative) muscle fibers. HFF diets induced autophagy as assessed by LC3I and LC3II, and inflammation, as assessed by IL-1a. No differences in body composition were observed, and there was no change in insulin sensitivity, but HFF diets increased several plasma acylcarnitines and decreased expression of lipid oxidation regulators PGC1a and CPT1, suggesting disruption of skeletal muscle metabolism. Our results show that an HFF diet fed to juvenile Iberian pigs produces a less oxidative skeletal muscle phenotype, similar to a detraining effect, and reduces the capacity to use lipid as fuel, even in the absence of insulin resistance and obesity.