Abstract
Pharmacological treatment modalities for non‐alcoholic fatty liver disease (NAFLD) and steatohepatitis (NASH) are scarce, and discoveries are challenged by lack of predictive animal models adequately reflecting severe human disease stages and co‐morbidities such as obesity and type 2 diabetes. To mimic human NAFLD/NASH etiology, many preclinical models rely on specific dietary components, though metabolism may differ considerably between species, potentially affecting outcomes and limiting comparability between studies. Consequently, understanding the physiological effects of dietary components is critical for high translational validity. This study investigated the effects of high fat, cholesterol, and carbohydrate sources on NASH development and metabolic outcomes in guinea pigs. Diet groups (n = 8/group) included: low‐fat low‐starch (LF‐LSt), low‐fat high-starch (LF‐HSt), high‐fat (HF) or HF with 4.2%, or 8.4% sugar water supplementation. The results showed that caloric compensation in HF animals supplied with sugar water led to reduced feed intake and a milder NASH phenotype compared to HF. The HF group displayed advanced NASH, weight gain and glucose intolerance compared to LF‐LSt animals, but not LF‐HSt, indicating an undesirable effect of starch in the control diet. Our findings support the HF guinea pig as a model of advanced NASH and highlights the importance in considering carbohydrate sources in preclinical studies of NAFLD.
Originalsprog | Engelsk |
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Artikelnummer | 2523 |
Tidsskrift | Nutrients |
Vol/bind | 13 |
Udgave nummer | 8 |
ISSN | 2072-6643 |
DOI | |
Status | Udgivet - 2021 |
Bibliografisk note
Funding Information:Acknowledgments: We would like to thank Ricki Thanning, Chichi N. Oskarsson and Anders A. Larsen for excellent technical support. This work was funded by the LifePharm Centre of In Vivo Pharmacology at the University of Copenhagen.
Funding Information:
Conflicts of Interest: J.S.‐R., D.H.I. and J.L. were supported in part by the LifePharm Centre of In Vivo Pharmacology, which has received funding from Novo Nordisk A/S. The funder had no role in experimental design, acquisition, analysis and interpretation of data, writing the manuscript or the decision to publish. M.L. is employed by Novo Nordisk A/S.
Publisher Copyright:
© 2021 by the authors. Licensee MDPI, Basel, Switzerland.