Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes
Open accessAbstract
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.
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The effect of high carbohydrate and low protein to increase FGF21 appears to be regulated independently.
“the effect of high carbohydrate and low protein to increase FGF21 appears to be regulated independently”
From FGF21 and the physiological regulation of macronutrient preference (2020) · cites this paper as [162]
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FGF21 Signals Protein Status to the Brain and Adaptively Regulates Food Choice and Metabolism
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Self-citationFGF21 and the physiological regulation of macronutrient preference
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- Authors
- Laeger, T., Castaño-Martinez, T., Werno, M. W., Japtok, L., Baumeier, C., Jonas, W., Kleuser, B., & Schürmann, A.
- Affiliations
- German Center for Diabetes Research (DE)
- University of Potsdam (DE)
- Corresponding author
- Schürmann, Annette
- Venue
- Diabetologia
- Published
- 2018-03-17
- Volume
- 61
- Issue
- 6
- Pages
- 1459-1469
- ISSN
- 0012-186X (ISSN-L)
- 1432-0428
- PMC
- PMC6449005
- OpenAlex
- W2790540275
- Cited by
- 17
- References
- 40
- Citations by year
- 2025: 3 · 2024: 1 · 2023: 1 · 2022: 2 · 2021: 4 · 2020: 2 · 2019: 3 · 2018: 1
- FWCI
- 1.72
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Diabetologia (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- publish.UP (University of Potsdam) (submittedVersion, cc-by)
- Funders
- German Ministry of Education and Research and the Brandenburg State (82DZD00302)
- Deutsche Forschungsgemeinschaft (LA 3042/4-1)
- Topics
- Health Sciences › Medicine › Physiology › Dietary Effects on Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Fibroblast Growth Factor Research
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diet, Metabolism, and Disease
- Keywords
- protein restriction, type 2 diabetes, dietary carbohydrates, high-fat diet, FGF21, hyperglycemia, beta cell destruction, energy expenditure, NZO mice, obesity, glucose tolerance
- MeSH terms
- Adipose Tissue, Animals, Blood Glucose, Body Weight, Diabetes Mellitus, Experimental, Diabetes Mellitus, Type 2, Dietary Carbohydrates, Energy Metabolism, Fibroblast Growth Factors, Glucose Tolerance Test, Insulin, Insulin Resistance, Male, Mice, Obese, Mice, Transgenic, Obesity, Diet, Protein-Restricted, Mice
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