Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes
- Aims/hypothesis Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. Methods We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Results Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure.Aims/hypothesis Low-protein diets are well known to improve glucose tolerance and increase energy expenditure. Increases in circulating fibroblast growth factor 21 (FGF21) have been implicated as a potential underlying mechanism. Methods We aimed to test whether low-protein diets in the context of a high-carbohydrate or high-fat regimen would also protect against type 2 diabetes in New Zealand Obese (NZO) mice used as a model of polygenetic obesity and type 2 diabetes. Mice were placed on high-fat diets that provided protein at control (16 kJ%; CON) or low (4 kJ%; low-protein/high-carbohydrate [LP/HC] or low-protein/high-fat [LP/HF]) levels. Results Protein restriction prevented the onset of hyperglycaemia and beta cell loss despite increased food intake and fat mass. The effect was seen only under conditions of a lower carbohydrate/fat ratio (LP/HF). When the carbohydrate/fat ratio was high (LP/HC), mice developed type 2 diabetes despite the robustly elevated hepatic FGF21 secretion and increased energy expenditure. Conclusion/interpretation Prevention of type 2 diabetes through protein restriction, without lowering food intake and body fat mass, is compromised by high dietary carbohydrates. Increased FGF21 levels and elevated energy expenditure do not protect against hyperglycaemia and type 2 diabetes per se.…
| Author details: | Thomas LaegerORCiDGND, Teresa Castano-Martinez, Martin W. Werno, Lukasz JaptokGND, Christian BaumeierGND, Wenke JonasORCiDGND, Burkhard KleuserORCiDGND, Annette SchürmannORCiDGND |
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| DOI: | https://doi.org/10.1007/s00125-018-4595-1 |
| ISSN: | 0012-186X |
| ISSN: | 1432-0428 |
| Pubmed ID: | https://pubmed.ncbi.nlm.nih.gov/29550873 |
| Title of parent work (English): | Diabetologia : journal of the European Association for the Study of Diabetes (EASD) |
| Publisher: | Springer |
| Place of publishing: | New York |
| Publication type: | Article |
| Language: | English |
| Date of first publication: | 2018/03/17 |
| Publication year: | 2018 |
| Release date: | 2021/11/22 |
| Tag: | Energy expenditure; FGF21; Hyperglycaemia; Insulin resistance; NZO; Obesity; Protein restriction |
| Volume: | 61 |
| Issue: | 6 |
| Number of pages: | 11 |
| First page: | 1459 |
| Last Page: | 1469 |
| Funding institution: | German Ministry of Education and ResearchFederal Ministry of Education & Research (BMBF); Brandenburg State (DZD) [82DZD00302]; Deutsche Forschungsgemeinschaft (DFG)German Research Foundation (DFG) [LA 3042/3-1, LA 3042/4-1] |
| Organizational units: | Mathematisch-Naturwissenschaftliche Fakultät / Institut für Ernährungswissenschaft |
| DDC classification: | 5 Naturwissenschaften und Mathematik / 57 Biowissenschaften; Biologie / 570 Biowissenschaften; Biologie |
| License (German): |  CC-BY - Namensnennung 4.0 International |
