Abstract

Background: The objective of this study is to determine the role of mitochondrial oxidative stress in the dysbiosis associated with a high fat diet in rats. In addition, the impact of gut microbiota (GM) in the cardiometabolic consequences of diet-induced obesity in rats has been evaluated. Methods: Male Wistar rats were fed either a high fat diet (HFD) or a control (CT) one for 6 weeks. At the third week, one-half of the animals of each group were treated with the mitochondrial antioxidant MitoTempo (MT; 0.7 mgKg−1day−1 i.p). Results: Animals fed an HFD showed a lower microbiota evenness and diversity in comparison to CT rats. This dysbiosis is characterized by a decrease in Firmicutes/Bacteroidetes ratio and relevant changes at family and genera compared with the CT group. This was accompanied by a reduction in colonic mucin-secreting goblet cells. These changes were reversed by MT treatment. The abundance of certain genera could also be relevant in the metabolic consequences of obesity, as well as in the occurrence of cardiac fibrosis associated with obesity. Conclusions: These results support an interaction between GM and mitochondrial oxidative stress and its relation with development of cardiac fibrosis, suggesting new approaches in the management of obesity-related cardiometabolic consequences.

Highlights

  • Nutrition is a key modulator of oxidative stress in the human body

  • We evaluated the impact of a high fat diet (HFD) on fecal microbiota composition and whether this effect could be modified by the administration of a mitochondrial targeted antioxidant

  • The administration of the mitochondrial antioxidant MT to HFD rats reduced the increase in Effects of MitoTempo

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Summary

Introduction

Nutrition is a key modulator of oxidative stress in the human body. Even under physiological conditions, nutrient intake is accompanied by a postprandial oxidative stress, with mitochondria being the major source of reactive oxygen species (ROS) [1]. Clinical and experimental studies have demonstrated that mitochondrial dysfunction can participate in the deleterious consequences of several pathological conditions, including obesity [5,6,7]. The objective of this study is to determine the role of mitochondrial oxidative stress in the dysbiosis associated with a high fat diet in rats. Results: Animals fed an HFD showed a lower microbiota evenness and diversity in comparison to CT rats. This dysbiosis is characterized by a decrease in Firmicutes/Bacteroidetes ratio and relevant changes at family and genera compared with the CT group

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