Distinct Influence of Hypercaloric Diets Predominant with Fat or Fat and Sucrose on Adipose Tissue and Liver Inflammation in Mice

Caíque S. M. Fonseca,Joshua E. Basford,Eddy S. Konaniah,James G. Cash,Vera L. M. Lima,David G. Kuhel,David Y. Hui

doi:10.3390/molecules25194369

Abstract

Overfeeding of a hypercaloric diet leads to obesity, diabetes, chronic inflammation, and fatty liver disease. Although limiting fat or carbohydrate intake is the cornerstone for obesity management, whether lowering fat or reducing carbohydrate intake is more effective for health management remains controversial. This study used murine models to determine how dietary fat and carbohydrates may influence metabolic disease manifestation. Age-matched C57BL/6J mice were fed 2 hypercaloric diets with similar caloric content, one with very high fat and low carbohydrate content (VHF) and the other with moderately high fat levels with high sucrose content (HFHS) for 12 weeks. Both groups gained more weight and displayed hypercholesterolemia, hyperglycemia, hyperinsulinemia, and liver steatosis compared to mice fed a normal low-fat (LF) diet. Interestingly, the VHF-fed mice showed a more robust adipose tissue inflammation compared to HFHS-fed mice, whereas HFHS-fed mice showed liver fibrosis and inflammation that was not observed in VHF-fed mice. Taken together, these results indicate macronutrient-specific tissue inflammation with excess dietary fat provoking adipose tissue inflammation, whereas moderately high dietary fat with extra sucrose is necessary and sufficient for hepatosteatosis advancement to steatohepatitis. Hence, liver and adipose tissues respond to dietary fat and sucrose in opposite manners, yet both macronutrients are contributing factors to metabolic diseases.

Highlights

Chronic overfeeding of a hypercaloric diet that exceeds energy expenditure and storage can cause metabolic imbalance that leads to cellular and tissue dysfunction and disease.Worldwide, it is estimated that there are 1.46 billion overweight adults and more than 500 million obese individuals [1]
high fat with excess sucrose (HFHS) diets displayed significant body weight gain and adiposity compared to low fat (LF)-fed mice, but no difference in body weight was observed between very high fat (VHF)- and HFHS-fed mice (Figure 1C)
The most popular diets among the laboratories include the high-fat diet-induced obesity (DIO) diet that contains 5.21 kcal/gm with 60% of calories derived from fat and 6.8% calories derived from sucrose, the Western diet that contains 4.7 kcal/gm with 41% calories derived from fat and 29%

Summary

Introduction

It is estimated that there are 1.46 billion overweight adults and more than 500 million obese individuals [1]. Such pandemic is associated with several comorbidities, having a crucial causative role in insulin resistance, diabetes mellitus, metabolic syndrome, and non-alcoholic liver disease (NAFLD) [2,3]. NAFLD [6], increasing evidence shows a significant prevalence of NAFLD in nonobese individuals [7]. Both obesity and NAFLD are characterized by excess lipid accumulation in ectopic tissues and are key components of the metabolic syndrome. Given the interplay between excess tissue lipid accumulation and metabolic disease manifestation, an integrated approach to identify the etiology of these chronic inflammatory diseases is of great interest

Objectives

Methods

Results

Discussion

Conclusion