Effects of different diets used in diet-induced obesity models on insulin resistance and vascular dysfunction in C57BL/6 mice

Philipp Lang,Ning Xia,Solveig Hasselwander,Huige Li

doi:10.1038/s41598-019-55987-x

Abstract

The aim of the present study was to compare different diets used to induce obesity in a head-to-head manner with a focus on insulin resistance and vascular dysfunction. Male C57BL/6J mice were put on standard chow diet (SCD), normal-fat diet (NFD), cafeteria diet (CAF) or high-fat diet (HFD) for 12 weeks starting at the age of 6 weeks. Both CAF and HFD led to obesity (weight gain of 179% and 194%, respectively), glucose intolerance and insulin resistance to a comparable extent. In aortas containing perivascular adipose tissue (PVAT), acetylcholine-induced vasodilation was best in the NFD group and worst in the CAF group. Reduced phosphorylation of endothelial nitric oxide synthase at serine 1177 was observed in both CAF and HFD groups. Plasma coagulation activity was highest in the HFD group and lowest in the SCD group. Even the NFD group had significantly higher coagulation activity than the SCD group. In conclusions, CAF and HFD are both reliable mouse diets in inducing visceral obesity, glucose intolerance and insulin resistance. CAF is more effective than HFD in causing PVAT dysfunction and vascular dysfunction, whereas hypercoagulability was mostly evident in the HFD group. Coagulation activity was higher in NFD than NCD group.

Highlights

The aim of the present study was to compare different diets used to induce obesity in a head-to-head manner with a focus on insulin resistance and vascular dysfunction
cafeteria diet (CAF) is more effective than high-fat diet (HFD) in causing perivascular adipose tissue (PVAT) dysfunction and vascular dysfunction, whereas hypercoagulability was mostly evident in the HFD group
The food consumption in gram was lower in normal-fat diet (NFD) (3.26 g per day per mouse), HFD (2.84 g per day per mouse) and CAF (2.76 g per day per mouse) groups compared to standard chow diet (SCD) (2.66 g per day per mouse) (Table 3, Fig. 1A)

Summary

Introduction

The aim of the present study was to compare different diets used to induce obesity in a head-to-head manner with a focus on insulin resistance and vascular dysfunction. Male C57BL/6J mice were put on standard chow diet (SCD), normal-fat diet (NFD), cafeteria diet (CAF) or high-fat diet (HFD) for 12 weeks starting at the age of 6 weeks. Both CAF and HFD led to obesity (weight gain of 179% and 194%, respectively), glucose intolerance and insulin resistance to a comparable extent. Since complications from obesity such as diabetes and cardiovascular disease usually require decades to develop, surrogate animal models are indispensable for studying the molecular aspects of obesity and its pathophysiological effects[5] Counted among those are rodent models such as genetic loss-of-function mutations, transgenic gain-of-function mutations, polygenic models and different environmental exposure models[5,6,7]. Diet-induced obesity (DIO) models represent the best fit for comparison to human obesity related pathologies[5,6,7]

Objectives

Methods

Results

Conclusion