TY - JOUR

T1 - Differential effects of dietary components on glucose intolerance and non‐alcoholic steatohepatitis

AU - Skat‐rørdam, Josephine

AU - Ipsen, David Højland

AU - Hardam, Patrick Duncan

AU - Latta, Markus

AU - Lykkesfeldt, Jens

AU - Tveden‐nyborg, Pernille

N1 - Publisher Copyright: © 2021 by the authors. Licensee MDPI, Basel, Switzerland.

PY - 2021

Y1 - 2021

N2 - 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.

AB - 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.

KW - Diet

KW - Glucose intolerance

KW - NASH

KW - Soft drink

KW - Starch

U2 - 10.3390/nu13082523

DO - 10.3390/nu13082523

M3 - Journal article

C2 - 34444683

AN - SCOPUS:85110727297

VL - 13

JO - Nutrients

JF - Nutrients

SN - 2072-6643

IS - 8

M1 - 2523

ER -