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Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease.
Int J Mol Sci. 2020 Dec 01; 21(23)IJ

Abstract

Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD.

Authors+Show Affiliations

Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Group on the Molecular and Cell Biology of Lipids, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada.Group on the Molecular and Cell Biology of Lipids, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada.Group on the Molecular and Cell Biology of Lipids, Department of Agricultural, Food and Nutritional Science, University of Alberta, Edmonton, AB T6G 2R3, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada. Department of Pathology and Laboratory Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.Department of Physiology and Pharmacology, Schulich School of Medicine and Dentistry, Western University, London, ON N6A 5C1, Canada.

Pub Type(s)

Journal Article

Language

eng

PubMed ID

33271781

Citation

Wilson, Rachel B., et al. "Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation Without Significant Weight Loss in Obese Mice With Non-Alcoholic Fatty Liver Disease." International Journal of Molecular Sciences, vol. 21, no. 23, 2020.
Wilson RB, Zhang R, Chen YJ, et al. Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2020;21(23).
Wilson, R. B., Zhang, R., Chen, Y. J., Peters, K. M., Sawyez, C. G., Sutherland, B. G., Patel, K., Kennelly, J. P., Leonard, K. A., Jacobs, R. L., Wang, R., & Borradaile, N. M. (2020). Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease. International Journal of Molecular Sciences, 21(23). https://doi.org/10.3390/ijms21239156
Wilson RB, et al. Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation Without Significant Weight Loss in Obese Mice With Non-Alcoholic Fatty Liver Disease. Int J Mol Sci. 2020 Dec 1;21(23) PubMed PMID: 33271781.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Two-Week Isocaloric Time-Restricted Feeding Decreases Liver Inflammation without Significant Weight Loss in Obese Mice with Non-Alcoholic Fatty Liver Disease. AU - Wilson,Rachel B, AU - Zhang,Richard, AU - Chen,Yun Jin, AU - Peters,Kia M, AU - Sawyez,Cynthia G, AU - Sutherland,Brian G, AU - Patel,Krisha, AU - Kennelly,John P, AU - Leonard,Kelly-Ann, AU - Jacobs,René L, AU - Wang,Rennian, AU - Borradaile,Nica M, Y1 - 2020/12/01/ PY - 2020/11/02/received PY - 2020/11/27/revised PY - 2020/11/28/accepted PY - 2020/12/4/entrez PY - 2020/12/5/pubmed PY - 2021/3/10/medline KW - NAFLD KW - inflammation KW - liver KW - mouse KW - obesity JF - International journal of molecular sciences JO - Int J Mol Sci VL - 21 IS - 23 N2 - Prolonged, isocaloric, time-restricted feeding (TRF) protocols can promote weight loss, improve metabolic dysregulation, and mitigate non-alcoholic fatty liver disease (NAFLD). In addition, 3-day, severe caloric restriction can improve liver metabolism and glucose homeostasis prior to significant weight loss. Thus, we hypothesized that short-term, isocaloric TRF would improve NAFLD and characteristics of metabolic syndrome in diet-induced obese male mice. After 26 weeks of ad libitum access to western diet, mice either continued feeding ad libitum or were provided with access to the same quantity of western diet for 8 h daily, over the course of two weeks. Remarkably, this short-term TRF protocol modestly decreased liver tissue inflammation in the absence of changes in body weight or epidydimal fat mass. There were no changes in hepatic lipid accumulation or other characteristics of NAFLD. We observed no changes in liver lipid metabolism-related gene expression, despite increased plasma free fatty acids and decreased plasma triglycerides in the TRF group. However, liver Grp78 and Txnip expression were decreased with TRF suggesting hepatic endoplasmic reticulum (ER) stress and activation of inflammatory pathways may have been diminished. We conclude that two-week, isocaloric TRF can potentially decrease liver inflammation, without significant weight loss or reductions in hepatic steatosis, in obese mice with NAFLD. SN - 1422-0067 UR - https://www.unboundmedicine.com/medline/citation/33271781/Two_Week_Isocaloric_Time_Restricted_Feeding_Decreases_Liver_Inflammation_without_Significant_Weight_Loss_in_Obese_Mice_with_Non_Alcoholic_Fatty_Liver_Disease_ L2 - https://www.mdpi.com/resolver?pii=ijms21239156 DB - PRIME DP - Unbound Medicine ER -