Diet Dependence of Diabetes in the New Zealand Obese (NZO) Mouse: Total Fat, But not Fat Quality or Sucrose Accelerates and Aggravates Diabetes

Mirhashemi, F.; Scherneck, Stephan; Kluth, Oliver; Kaiser, Daniel R.; Vogel, Heike; Kluge, Reinhart; Schürmann, Annette; Neschen, Susanne; Joost, Hans‐Georg

doi:10.1055/s-0030-1263127

Cited by 19 publications

(19 citation statements)

References 22 publications

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“…The comparison of the effects of a semi-purified HF diet with a chow diet rather than with a semi-purified LF diet can show different changes in metabolic parameters [32]. Indeed chow has been found to be protective against the development of adiposity and insulin insensitivity probably due to its high fibre content [33]. Nonetheless, we recognise that in the present study the LF and HF semi-purified diets contain variable amounts of sucrose as well as fat which may lead to metabolic imbalances.…”

Section: Discussionmentioning

confidence: 99%

The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

et al. 2014

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High–fat (HF) diet-induced obesity and insulin insensitivity are associated with inflammation, particularly in white adipose tissue (WAT). However, insulin insensitivity is apparent within days of HF feeding when gains in adiposity and changes in markers of inflammation are relatively minor. To investigate further the effects of HF diet, C57Bl/6J mice were fed either a low (LF) or HF diet for 3 days to 16 weeks, or fed the HF-diet matched to the caloric intake of the LF diet (PF) for 3 days or 1 week, with the time course of glucose tolerance and inflammatory gene expression measured in liver, muscle and WAT. HF fed mice gained adiposity and liver lipid steadily over 16 weeks, but developed glucose intolerance, assessed by intraperitoneal glucose tolerance tests (IPGTT), in two phases. The first phase, after 3 days, resulted in a 50% increase in area under the curve (AUC) for HF and PF mice, which improved to 30% after 1 week and remained stable until 12 weeks. Between 12 and 16 weeks the difference in AUC increased to 60%, when gene markers of inflammation appeared in WAT and muscle but not in liver. Plasma proteomics were used to reveal an acute phase response at day 3. Data from PF mice reveals that glucose intolerance and the acute phase response are the result of the HF composition of the diet and increased caloric intake respectively. Thus, the initial increase in glucose intolerance due to a HF diet occurs concurrently with an acute phase response but these effects are caused by different properties of the diet. The second increase in glucose intolerance occurs between 12 - 16 weeks of HF diet and is correlated with WAT and muscle inflammation. Between these times glucose tolerance remains stable and markers of inflammation are undetectable.

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Section: Discussionmentioning

confidence: 99%

The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

et al. 2014

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“…By the age of 4-5 weeks, NZO mice exhibit insulin resistance in brown adipose tissue and skeletal muscle 239 . Notably, the macronutrient composition of the diet is important for the diabetogenic phenotype 240 . NZO mice fed a carbohydrate-free diet remain normoglycaemic despite marked insulin resistance and obesity 241 .…”

Section: Genetic Rodent Modelsmentioning

confidence: 99%

Animal models of obesity and diabetes mellitus

et al. 2018

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More than one-third of the worldwide population is overweight or obese and therefore at risk of developing type 2 diabetes mellitus. In order to mitigate this pandemic, safer and more potent therapeutics are urgently required. This necessitates the continued use of animal models to discover, validate and optimize novel therapeutics for their safe use in humans. In order to improve the transition from bench to bedside, researchers must not only carefully select the appropriate model but also draw the right conclusions. In this Review, we consolidate the key information on the currently available animal models of obesity and diabetes and highlight the advantages, limitations and important caveats of each of these models.

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“…The New Zealand Obese (NZO, NZO/HlLtJ) mouse is a polygenic model of diabetes that exhibits a higher propensity to develop hyperglycemia when fed a high fat diet [14,15]. NZO mice fed a high fat diet (DM, 30% fat by weight, Teklad Diet 04059) was used to model type 2 diabetes.…”

Section: Animals and Treatmentsmentioning

confidence: 99%

Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus

et al. 2019

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Background: Hypertension and renal injury are common complications of type 2 diabetes mellitus (T2DM). Hyperglycemia stimulates renal proximal tubular angiotensinogen (AGT) expression via elevated oxidative stress contributing to the development of high blood pressure and diabetic nephropathy. The sodium glucose cotransporter 2 (SGLT2) in proximal tubules is responsible for the majority of glucose reabsorption by renal tubules. We tested the hypothesis that SGLT2 inhibition with canagliflozin (CANA) prevents intrarenal AGT augmentation and ameliorates kidney injury and hypertension in T2DM. Methods: We induced T2DM in New Zealand obese mice with a high fat diet (DM, 30% fat) with control mice receiving regular fat diet (ND, 4% fat). When DM mice exhibited > 350 mg/dL blood glucose levels, both DM- and ND-fed mice were treated with 10 mg/kg/day CANA or vehicle by oral gavage for 6 weeks. We evaluated intrarenal AGT, blood pressure, and the development of kidney injury. Results: Systolic blood pressure in DM mice (133.9 ± 2.0 mm Hg) was normalized by CANA (113.9 ± 4.0 mm Hg). CANA treatment ameliorated hyperglycemia-associated augmentation of renal AGT mRNA (148 ± 21 copies/ng RNA in DM, and 90 ± 16 copies/ng RNA in DM + CANA) and protein levels as well as elevation of urinary 8-isoprostane levels. Tubular fibrosis in DM mice (3.4 ± 0.9-fold, fibrotic score, ratio to ND) was suppressed by CANA (0.9 ± 0.3-fold). Furthermore, CANA attenuated DM associated increased macrophage infiltration and cell proliferation in kidneys of DM mice. Conclusions: CANA prevents intrarenal AGT upregulation and oxidative stress and which may mitigate high blood pressure, renal tubular fibrosis, and renal inflammation in T2DM.

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Diet Dependence of Diabetes in the New Zealand Obese (NZO) Mouse: Total Fat, But not Fat Quality or Sucrose Accelerates and Aggravates Diabetes

Cited by 19 publications

References 22 publications

The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

The Development of Diet-Induced Obesity and Glucose Intolerance in C57Bl/6 Mice on a High-Fat Diet Consists of Distinct Phases

Animal models of obesity and diabetes mellitus

Canagliflozin Prevents Intrarenal Angiotensinogen Augmentation and Mitigates Kidney Injury and Hypertension in Mouse Model of Type 2 Diabetes Mellitus

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