Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice
In diabetes, pancreatic β-cells gradually lose their ability to secrete insulin with disease progression. β-cell dysfunction is a contributing factor to diabetes severity. Recently, islet cell heterogeneity, exemplified by β-cell dedifferentiation and identified in diabetic animals, has attracted at...
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MDPI AG
2024-03-01
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| author | Xiao Lei Emi Ishida Satoshi Yoshino Shunichi Matsumoto Kazuhiko Horiguchi Eijiro Yamada |
| author_facet | Xiao Lei Emi Ishida Satoshi Yoshino Shunichi Matsumoto Kazuhiko Horiguchi Eijiro Yamada |
| author_sort | Xiao Lei |
| collection | DOAJ |
| description | In diabetes, pancreatic β-cells gradually lose their ability to secrete insulin with disease progression. β-cell dysfunction is a contributing factor to diabetes severity. Recently, islet cell heterogeneity, exemplified by β-cell dedifferentiation and identified in diabetic animals, has attracted attention as an underlying molecular mechanism of β-cell dysfunction. Previously, we reported β-cell dedifferentiation suppression by calorie restriction, not by reducing hyperglycemia using hypoglycemic agents (including sodium-glucose cotransporter inhibitors), in an obese diabetic mice model (<i>db</i>/<i>db</i>). Here, to explore further mechanisms of the effects of food intake on β-cell function, <i>db</i>/<i>db</i> mice were fed either a high-carbohydrate/low-fat diet (db-HC) or a low-carbohydrate/high-fat diet (db-HF) using similar calorie restriction regimens. After one month of intervention, body weight reduced, and glucose intolerance improved to a similar extent in the db-HC and db-HF groups. However, β-cell dedifferentiation did not improve in the db-HC group, and β-cell mass compensatory increase occurred in this group. More prominent fat accumulation occurred in the db-HC group livers. The expression levels of genes related to lipid metabolism, mainly regulated by peroxisome proliferator-activated receptor α and γ, differed significantly between groups. In conclusion, the fat/carbohydrate ratio in food during calorie restriction in obese mice affected both liver lipid metabolism and β-cell dedifferentiation. |
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| language | English |
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| series | Nutrients |
| spelling | doaj.art-b97519c75e3a40f4b5b4d3be9075dd6b2024-04-12T13:24:19ZengMDPI AGNutrients2072-66432024-03-0116799510.3390/nu16070995Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic MiceXiao Lei0Emi Ishida1Satoshi Yoshino2Shunichi Matsumoto3Kazuhiko Horiguchi4Eijiro Yamada5Department of Internal Medicine, Division of Endocrinology and Metabolism, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, JapanDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, JapanDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, JapanDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, JapanDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, JapanDepartment of Internal Medicine, Division of Endocrinology and Metabolism, Graduate School of Medicine, Gunma University, Maebashi 371-8511, Gunma, JapanIn diabetes, pancreatic β-cells gradually lose their ability to secrete insulin with disease progression. β-cell dysfunction is a contributing factor to diabetes severity. Recently, islet cell heterogeneity, exemplified by β-cell dedifferentiation and identified in diabetic animals, has attracted attention as an underlying molecular mechanism of β-cell dysfunction. Previously, we reported β-cell dedifferentiation suppression by calorie restriction, not by reducing hyperglycemia using hypoglycemic agents (including sodium-glucose cotransporter inhibitors), in an obese diabetic mice model (<i>db</i>/<i>db</i>). Here, to explore further mechanisms of the effects of food intake on β-cell function, <i>db</i>/<i>db</i> mice were fed either a high-carbohydrate/low-fat diet (db-HC) or a low-carbohydrate/high-fat diet (db-HF) using similar calorie restriction regimens. After one month of intervention, body weight reduced, and glucose intolerance improved to a similar extent in the db-HC and db-HF groups. However, β-cell dedifferentiation did not improve in the db-HC group, and β-cell mass compensatory increase occurred in this group. More prominent fat accumulation occurred in the db-HC group livers. The expression levels of genes related to lipid metabolism, mainly regulated by peroxisome proliferator-activated receptor α and γ, differed significantly between groups. In conclusion, the fat/carbohydrate ratio in food during calorie restriction in obese mice affected both liver lipid metabolism and β-cell dedifferentiation.https://www.mdpi.com/2072-6643/16/7/995diabetesdyslipidemiaobesity<i>db</i>/<i>db</i> micecalorie restrictioncarbohydrate/fat ratio |
| spellingShingle | Xiao Lei Emi Ishida Satoshi Yoshino Shunichi Matsumoto Kazuhiko Horiguchi Eijiro Yamada Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice Nutrients diabetes dyslipidemia obesity <i>db</i>/<i>db</i> mice calorie restriction carbohydrate/fat ratio |
| title | Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice |
| title_full | Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice |
| title_fullStr | Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice |
| title_full_unstemmed | Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice |
| title_short | Calorie Restriction Using High-Fat/Low-Carbohydrate Diet Suppresses Liver Fat Accumulation and Pancreatic Beta-Cell Dedifferentiation in Obese Diabetic Mice |
| title_sort | calorie restriction using high fat low carbohydrate diet suppresses liver fat accumulation and pancreatic beta cell dedifferentiation in obese diabetic mice |
| topic | diabetes dyslipidemia obesity <i>db</i>/<i>db</i> mice calorie restriction carbohydrate/fat ratio |
| url | https://www.mdpi.com/2072-6643/16/7/995 |
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