Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis
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 mi...
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MDPI AG
2021-07-01
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| Online Access: | https://www.mdpi.com/2072-6643/13/8/2523 |
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| author | Josephine Skat-Rørdam David Højland Ipsen Patrick Duncan Hardam Markus Latta Jens Lykkesfeldt Pernille Tveden-Nyborg |
| author_facet | Josephine Skat-Rørdam David Højland Ipsen Patrick Duncan Hardam Markus Latta Jens Lykkesfeldt Pernille Tveden-Nyborg |
| author_sort | Josephine Skat-Rørdam |
| collection | DOAJ |
| description | 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 (<i>n</i> = 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. |
| first_indexed | 2024-03-10T08:31:06Z |
| format | Article |
| id | doaj.art-4bf71c9b92f54267a739907dafbdde37 |
| institution | Directory Open Access Journal |
| issn | 2072-6643 |
| language | English |
| last_indexed | 2024-03-10T08:31:06Z |
| publishDate | 2021-07-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Nutrients |
| spelling | doaj.art-4bf71c9b92f54267a739907dafbdde372023-11-22T09:01:59ZengMDPI AGNutrients2072-66432021-07-01138252310.3390/nu13082523Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic SteatohepatitisJosephine Skat-Rørdam0David Højland Ipsen1Patrick Duncan Hardam2Markus Latta3Jens Lykkesfeldt4Pernille Tveden-Nyborg5Section of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkLiver Disease Research, Global Drug Discovery, Novo Nordisk A/S, 2880 Copenhagen, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkSection of Experimental Animal Models, Department of Veterinary and Animal Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, 1870 Frederiksberg, DenmarkPharmacological 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 (<i>n</i> = 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.https://www.mdpi.com/2072-6643/13/8/2523NASHglucose intolerancedietstarchsoft drink |
| spellingShingle | Josephine Skat-Rørdam David Højland Ipsen Patrick Duncan Hardam Markus Latta Jens Lykkesfeldt Pernille Tveden-Nyborg Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis Nutrients NASH glucose intolerance diet starch soft drink |
| title | Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis |
| title_full | Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis |
| title_fullStr | Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis |
| title_full_unstemmed | Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis |
| title_short | Differential Effects of Dietary Components on Glucose Intolerance and Non-Alcoholic Steatohepatitis |
| title_sort | differential effects of dietary components on glucose intolerance and non alcoholic steatohepatitis |
| topic | NASH glucose intolerance diet starch soft drink |
| url | https://www.mdpi.com/2072-6643/13/8/2523 |
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