TY  - JOUR
A1  - John, Cathleen
A1  - Grune, Jana
A1  - Ott, Christiane
A1  - Nowotny, Kerstin
A1  - Deubel, Stefanie
A1  - Kühne, Arne
A1  - Schubert, Carola
A1  - Kintscher, Ulrich
A1  - Regitz-Zagrosek, Vera
A1  - Grune, Tilman
T1  - Sex Differences in Cardiac Mitochondria in the New Zealand Obese Mouse
JF  - Frontiers in Endocrinology
N2  - Background: Obesity is a risk factor for diseases including type 2 diabetes mellitus (T2DM) and cardiovascular disorders. Diabetes itself contributes to cardiac damage. Thus, studying cardiovascular events and establishing therapeutic intervention in the period of type T2DM onset and manifestation are of highest importance. Mitochondrial dysfunction is one of the pathophysiological mechanisms leading to impaired cardiac function. Methods: An adequate animal model for studying pathophysiology of T2DM is the New Zealand Obese (NZO) mouse. These mice were maintained on a high-fat diet (HFD) without carbohydrates for 13 weeks followed by 4 week HFD with carbohydrates. NZO mice developed severe obesity and only male mice developed manifest T2DM. We determined cardiac phenotypes and mitochondrial function as well as cardiomyocyte signaling in this model. Results: The development of an obese phenotype and T2DM in male mice was accompanied by an impaired systolic function as judged by echocardiography and MyH6/7 expression. Moreover, the mitochondrial function only in male NZO hearts was significantly reduced and ERK1/2 and AMPK protein levels were altered. Conclusions: This is the first report demonstrating that the cardiac phenotype in male diabetic NZO mice is associated with impaired cardiac energy function and signaling events.
KW  - NZO
KW  - heart
KW  - obesity
KW  - mitochondrial function
KW  - echocardiography
KW  - systolic function
Y1  - 2018
U6  - https://doi.org/10.3389/fendo.2018.00732
SN  - 1664-2392
VL  - 9
PB  - Frontiers Research Foundation
CY  - Lausanne
ER  - 
TY  - JOUR
A1  - Laeger, Thomas
A1  - Castano-Martinez, Teresa
A1  - Werno, Martin W.
A1  - Japtok, Lukasz
A1  - Baumeier, Christian
A1  - Jonas, Wenke
A1  - Kleuser, Burkhard
A1  - Schürmann, Annette
T1  - Dietary carbohydrates impair the protective effect of protein restriction against diabetes in NZO mice used as a model of type 2 diabetes
JF  - Diabetologia : journal of the European Association for the Study of Diabetes (EASD)
N2  - 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.
KW  - Energy expenditure
KW  - FGF21
KW  - Hyperglycaemia
KW  - Insulin resistance
KW  - NZO
KW  - Obesity
KW  - Protein restriction
Y1  - 2018
U6  - https://doi.org/10.1007/s00125-018-4595-1
SN  - 0012-186X
SN  - 1432-0428
VL  - 61
IS  - 6
SP  - 1459
EP  - 1469
PB  - Springer
CY  - New York
ER  -