High-fat diets rich in ω-3 or ω-6 polyunsaturated fatty acids have distinct effects on lipid profiles and lipid peroxidation in mice selected for either high body weight or leanness

Abstract

Objective

The aim of the study is to determine the response of muscle lipid peroxidation and the fatty-acid profile of three groups of mice—high body weight (DU6) obesity-prone mice, high treadmill performance (DUhTP) lean mice, and unselected control mice (DUK) fed high-fat diets (HFDs) rich in ω-3 or ω-6 polyunsaturated fatty acids (PUFA).

Methods

The isocaloric HFDs were enriched with either ω-3 PUFA (27% fish oil, ω-3 HFD) or ω-6 PUFA (27% sunflower oil, ω-6 HFD), and the control group was fed standard chow (7.2% fat). Statistical calculations were done with procedure GLM of SAS.

Results

As expected, the ω-3 and ω-6 PUFA-rich HFDs showed significant effects on fatty-acid concentrations of skeletal muscle in all three lines of mice compared with the standard chow. The investigations of muscle lipid peroxidation revealed that the ω-3 PUFA-rich HFD caused the highest lipid peroxidation values in muscle of lean DUhTP mice and unselected control DUK mice. However, lower lipid peroxidation levels were observed in the obesity-prone DU6 mice. In contrast, the ω-6 PUFA-rich HFD did not influence lipid peroxidation in muscle of any of the different lines of mice. The present study suggests that a higher overall antioxidant capacity in the muscle tissue of obesity-prone DU6 mice may lead to lower levels of reactive oxygen species formation by ω-3 PUFA-rich HFDs in comparison with lean DUhTP mice.

Conclusion

These studies raise the possibility that obesity per se may be protective against oxidative damage when high ω-3 PUFA diets are used.

Introduction

Oxidative stress characterizes an imbalance between the systemic appearance of reactive oxygen species (ROS) and the ability of a biological system to readily detoxify the reactive intermediate products or to repair the resulting damage. Oxidative stress induced by high-fat diets (HFDs) and the resulting lipid peroxidation combined with the formation of lipid peroxides have been associated with a range of diseases, such as type 2 diabetes mellitus, arteriosclerosis, Alzheimer's disease, and cancer [1], [2]. Furthermore, the amount of dietary fat intake and the composition of the dietary fat can influence the onset and/or progression of cardiovascular disease and other health outcomes [3]. There is compelling evidence for the benefits of dietary ω-3 long-chain polyunsaturated fatty acid (ω-3 PUFA) on inflammation and metabolic and cardiovascular health. Urgent attention is therefore needed to advance the knowledge of how fatty-acid compositions of our diets influence long-term health. The trends in Western diets, combined with a shift toward higher intake of vegetable oils rich in ω-6 PUFA, have resulted in an overall increase in total fat intake [4], [5]. Dietary and de novo synthesized ω-3 and ω-6 PUFA in body tissues are highly susceptible to lipid peroxidation by ROS originating from endogenous or exogenous sources. Although antioxidant enzymes such as superoxide dismutase (SOD), catalase (CAT), and glutathione peroxidase (GPx) reduce the cellular damage caused by common free radicals in the body, the activity of these antioxidant enzymes is significantly diminished as adipose tissue increases [6]. Furthermore, high ROS production and a decrease in antioxidant capacity lead to damage of biomolecules directly or initiate chain reactions, in which ROS are passed from one molecule to another, resulting in extensive damage to lipids and proteins and thus impairing normal cell structure and function [6], [7], [8]. Mice from long-term selection lines offer unique models for studying influences of genetic factors in determining specific dietary effects on oxidative stress induced by HFDs and tissue lipid peroxidation. Increased formation of ROS has been observed in various tissues from mice fed HFD [9], [10]. Additionally, some studies have shown that high-fat and high-cholesterol–containing diets also promote oxidative stress in mice through formation of lipid peroxides [10], [11]. Mice lines with distinct biological traits, that is, the high body weight (DU6) obesity-prone mice and the high treadmill performance (DUhTP) lean mice, were generated by long-term selection from a common genetic pool of outbred mice (DUK) [12], [13], [14]. Recently, we described the metabolic responses to an HFD rich in either ω-3 or ω-6 PUFA on the insulin-signaling pathways in liver, muscle, and abdominal adipose tissue in DU6 and DUhTP mice [15]. The specific metabolic responses in body tissues to an HFD enriched with either ω-3 or ω-6 PUFA differed markedly between the two selection lines despite similar calorie intake.

The aim of this study was to investigate lipid peroxidation and fatty-acid profiles of muscle tissue and the responses to HFDs rich in either ω-3 or ω-6 PUFA in DU6 obesity-prone mice and DUhTP lean mice with distinct biological traits and compare them with the unselected control DUK line. We hypothesize that a higher overall antioxidant capacity in muscle tissue of obesity-prone DU6 mice may ameliorate the ROS formation in response to an ω-3 PUFA-rich HFD compared with the response observed in lean DUhTP mice. The work presented here advances the understanding of metabolic responses to HFDs rich in ω-3 and ω-6 PUFA and will show whether dietary changes influence muscle lipid peroxidation that could, in turn, influence long-term health outcomes.