Sucrose Counteracts the Anti-Inflammatory Effect of Fish Oil in Adipose Tissue and Increases Obesity Development in Mice

Tao Ma,Henriette Pilegaard,Stine Ringholm,Jonas Thue Treebak,Ha Thi Ngo,Haldis Haukås Lillefosse,Si Brask Sonne,Lise Madsen,Qin Hao,Karsten Kristiansen,Even Fjære,Rasmus Koefoed Petersen,Bjørn Liaset,Livar Frøyland,Aimin Xu

doi:10.1371/journal.pone.0021647

Abstract

BackgroundPolyunsaturated n-3 fatty acids (n-3 PUFAs) are reported to protect against high fat diet-induced obesity and inflammation in adipose tissue. Here we aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance.Methodology/Principal FindingsWe fed C57BL/6J mice a protein- (casein) or sucrose-based high fat diet supplemented with fish oil or corn oil for 9 weeks. Irrespective of the fatty acid source, mice fed diets rich in sucrose became obese whereas mice fed high protein diets remained lean. Inclusion of sucrose in the diet also counteracted the well-known anti-inflammatory effect of fish oil in adipose tissue, but did not impair the ability of fish oil to prevent accumulation of fat in the liver. Calculation of HOMA-IR indicated that mice fed high levels of proteins remained insulin sensitive, whereas insulin sensitivity was reduced in the obese mice fed sucrose irrespectively of the fat source. We show that a high fat diet decreased glucose tolerance in the mice independently of both obesity and dietary levels of n-3 PUFAs and sucrose. Of note, increasing the protein∶sucrose ratio in high fat diets decreased energy efficiency irrespective of fat source. This was accompanied by increased expression of Ppargc1a (peroxisome proliferator-activated receptor, gamma, coactivator 1 alpha) and increased gluconeogenesis in the fed state.Conclusions/SignificanceThe background diet influence the ability of n-3 PUFAs to protect against development of obesity, glucose intolerance and adipose tissue inflammation. High levels of dietary sucrose counteract the anti-inflammatory effect of fish oil in adipose tissue and increases obesity development in mice.

Highlights

Today it is recognized that the potentially harmful effects of high fat diets relates to the amount, and the type of dietary fatty acids
We aimed to examine whether the background diet exerts an influence on the ability of n-3 polyunsaturated fatty acids. doi (PUFA) to protect against glucose intolerance and adipose tissue inflammation
It is a general notion that intake of fish oil rich in n-3 PUFAs limits high fat diet-induced obesity in rodents, whereas diets rich in n-6 PUFAs have been associated with an increased propensity to develop obesity [6,26]

Summary

Introduction

Today it is recognized that the potentially harmful effects of high fat diets relates to the amount, and the type of dietary fatty acids. It is important to note, that more than 85% of the total dietary PUFA intake in Western diets today is vegetable n-6 PUFAs, mainly linoleic acid [3]. This is largely due to the high amount of linoleic acid in corn-, sunflower-, and soybean-oil used in both home-cooking and in industrially prepared food [4]. Animal studies have shown that feeding mice a diet containing the n-6 PUFA, linoleic acid, during the pregnancy-lactation period leads to obesity in the offspring [6] This effect, is prevented by inclusion of the n-3 PUFA a-linolenic acid in the diet [6]. We aimed to investigate if the amount of sucrose in the background diet influences the ability of n-3 PUFAs to protect against diet-induced obesity, adipose tissue inflammation and glucose intolerance

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