2018
DOI: 10.1007/s00125-018-4595-1
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Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes

Abstract: 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 p… Show more

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Cited by 13 publications
(20 citation statements)
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“…Therefore, if high carbohydrate were essential, we would not observe effects with the HFLP diet, yet both LP and HFLP robustly increase FGF21 and induce metabolic effects that are dependent on FGF21 and FGF21 signaling in the brain. Similar observations were made in the research by Laeger et al (2018) , in which LP diet increased FGF21, regardless of whether the diet was balanced by fat or carbohydrate. Thus, our data strongly demonstrate that the diets induce a state of protein restriction, leading to increases in FGF21, which acts in the brain to coordinate the metabolic response to protein restriction.…”
Section: Discussionsupporting
confidence: 87%
See 2 more Smart Citations
“…Therefore, if high carbohydrate were essential, we would not observe effects with the HFLP diet, yet both LP and HFLP robustly increase FGF21 and induce metabolic effects that are dependent on FGF21 and FGF21 signaling in the brain. Similar observations were made in the research by Laeger et al (2018) , in which LP diet increased FGF21, regardless of whether the diet was balanced by fat or carbohydrate. Thus, our data strongly demonstrate that the diets induce a state of protein restriction, leading to increases in FGF21, which acts in the brain to coordinate the metabolic response to protein restriction.…”
Section: Discussionsupporting
confidence: 87%
“…Dietary protein restriction improves glucose homeostasis in settings of diet induced obesity ( Cummings et al, 2018 ; Fontana et al, 2016 ; Laeger et al, 2018 ; Maida et al, 2016 , 2017 ; Solon-Biet et al, 2014 ) and represents an alternative nutritional strategy to general dietary (calorie) restriction. To directly compare the metabolic effect of protein restriction and dietary (food) restriction in obese mice, wild-type mice were fed either a 60% high-fat diet (HFD) ad libitum (HFCon), a 60% HFD that was low in protein (HFLP), or a diet-restriction group (HFDR), in which mice consumed HFCon but were food restricted to match body weight to the HFLP group.…”
Section: Resultsmentioning
confidence: 99%
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“…We and others have previously shown that dietary PR may reduce body weight by decreasing body fat gain, improving glucose tolerance, and increasing energy expenditure (EE), effects which are mediated by fibroblast growth factor 21 (FGF21) (25). Our group recently demonstrated in New Zealand obese (NZO) mice, a model for polygenic obesity and type 2 diabetes with the characteristic trait of pancreatic β-cell loss, that exogenous FGF21 treatment (6) and a dietary PR-induced increase in FGF21 plasma levels (7) prevented hyperglycemia and diabetes, despite hyperphagia.…”
mentioning
confidence: 99%
“…This slight increase in FGF21 concentration (0.8 ng/ml in NZO mice) may represent a compensatory mechanism for deteriorating glucose homeostasis (6). In rodents, restriction of dietary protein and methionine increases circulating FGF21 levels >4 and 8 ng/ml, respectively, after 4–7 d on PR or only 6 h on MR (2, 3, 5, 7, 24). As recently demonstrated by our group, exogenous FGF21 treatment (6) and dietary PR, which increases endogenous plasma FGF21 (7), prevent hyperglycemia and diabetes in NZO mice.…”
mentioning
confidence: 99%