Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs

Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weig...

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Main Authors: Qiang Zhang, Lingyan Xu, Jie Xia, Dongmei Wang, Min Qian, Shuzhe Ding
Format: Article
Language:English
Published: Wiley 2018-01-01
Series:PPAR Research
Online Access:http://dx.doi.org/10.1155/2018/4827643
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author Qiang Zhang
Lingyan Xu
Jie Xia
Dongmei Wang
Min Qian
Shuzhe Ding
author_facet Qiang Zhang
Lingyan Xu
Jie Xia
Dongmei Wang
Min Qian
Shuzhe Ding
author_sort Qiang Zhang
collection DOAJ
description Type 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPARγ and lipid synthetic genes, as well as enhancing PPARα and lipid β-oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes.
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spelling doaj-art-7a26986de7fa4c83bfdf688cdeb971942025-08-20T03:07:02ZengWileyPPAR Research1687-47571687-47652018-01-01201810.1155/2018/48276434827643Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene ProgramsQiang Zhang0Lingyan Xu1Jie Xia2Dongmei Wang3Min Qian4Shuzhe Ding5Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaKey Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaShanghai Key Laboratory of Regulatory Biology, Institute of Biomedical Sciences and School of Life Sciences, East China Normal University, Shanghai, ChinaKey Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai 200241, ChinaType 2 diabetes is a prevalent chronic disease arising as a serious public health problem worldwide. Diet intervention is considered to be a critical strategy in glycemic control of diabetic patients. Recently, the low-carbohydrate ketogenic diet is shown to be effective in glycemic control and weight loss. However, hepatic lipid accumulation could be observed in mice treated with ketogenic diet. On the other hand, exercise is a well-known approach for treating nonalcoholic fatty liver disease. We thus hypothesize that the combination of ketogenic diet and exercise could improve insulin sensitivity, while minimizing adverse effect of hepatic steatosis. In order to test this hypothesis, we established diabetic mice model with streptozotocin (STZ) and divided them into control group, ketogenic diet group, and ketogenic diet with aerobic exercise group. We found that after six weeks of intervention, mice treated with ketogenic diet and ketogenic diet combined with exercise both have lower body weights, HbAlc level, HOMA index, and improvements in insulin sensitivity, compared with diabetes group. In addition, mice in ketogenic diet intervention exhibited hepatic steatosis shown by serum and hepatic parameters, as well as histochemistry staining in the liver, which could be largely relieved by exercise. Furthermore, gene analysis revealed that ketogenic diet in combination with exercise reduced PPARγ and lipid synthetic genes, as well as enhancing PPARα and lipid β-oxidation gene program in the liver compared to those in ketogenic diet without exercise. Overall, the present study demonstrated that the combination of ketogenic diet and a moderate-intensity aerobic exercise intervention improved insulin sensitivity in diabetic mice, while avoiding hepatic steatosis, which provided a novel strategy in the combat of diabetes.http://dx.doi.org/10.1155/2018/4827643
spellingShingle Qiang Zhang
Lingyan Xu
Jie Xia
Dongmei Wang
Min Qian
Shuzhe Ding
Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs
PPAR Research
title Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs
title_full Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs
title_fullStr Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs
title_full_unstemmed Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs
title_short Treatment of Diabetic Mice with a Combination of Ketogenic Diet and Aerobic Exercise via Modulations of PPARs Gene Programs
title_sort treatment of diabetic mice with a combination of ketogenic diet and aerobic exercise via modulations of ppars gene programs
url http://dx.doi.org/10.1155/2018/4827643
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