Abstract

BackgroundExercise has been extensively utilised as an effective therapy for overweight- and obesity-associated changes that are linked to health complications. Several preclinical rodent studies have shown that treadmill exercise alongside an unhealthy diet improves metabolic health and microbiome composition. Furthermore, chronic exercise has been shown to alter hypothalamic and adipose tissue gene expression in diet-induced obesity. However, limited work has investigated whether treadmill exercise commenced following exposure to an obesogenic diet is sufficient to alter microbiome composition and metabolic health.MethodsTo address this gap in the literature, we fed rats a high-fat/high-sugar western-style cafeteria diet and assessed the effects of 4 weeks of treadmill exercise on adiposity, diet-induced gut dysbiosis, as well as hypothalamic and retroperitoneal white adipose tissue gene expression. Forty-eight male Sprague-Dawley rats were allocated to either regular chow or cafeteria diet and after 3 weeks half the rats on each diet were exposed to moderate treadmill exercise for 4 weeks while the remainder were exposed to a stationary treadmill.ResultsMicrobial species diversity was uniquely reduced in exercising chow-fed rats, while microbiome composition was only changed by cafeteria diet. Despite limited effects of exercise on overall microbiome composition, exercise increased inferred microbial functions involved in metabolism, reduced fat mass, and altered adipose and hypothalamic gene expression. After controlling for diet and exercise, adipose Il6 expression and liver triglyceride concentrations were significantly associated with global microbiome composition.ConclusionsModerate treadmill exercise induced subtle microbiome composition changes in chow-fed rats but did not overcome the microbiome changes induced by prolonged exposure to cafeteria diet. Predicted metabolic function of the gut microbiome was increased by exercise. The effects of exercise on the microbiome may be modulated by obesity severity. Future work should investigate whether exercise in combination with microbiome-modifying interventions can synergistically reduce diet- and obesity-associated comorbidities.

Highlights

  • Overweight and obesity leads to reductions in physical and mental health, and quality of life [1], resulting in increased direct and indirect costs to the global economy [2]

  • We aimed to investigate whether any changes in gut microbiome were associated with altered gene expression in white adipose tissue (WAT) and the hypothalamus, which are known to be affected by both obesogenic diets and exercise

  • Tukey honest significant difference (THSD) post-hoc comparisons showed that compared to Chow Sedentary (CSed) and Chow Exercise (CEx), Cafeteria Sedentary (CafSed) (p < 0.001 and p < 0.001) and Cafeteria Exercise (CafEx) (p = 0.038 and p < 0.001) gained significantly more weight over the exercise intervention

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Summary

Introduction

Overweight and obesity leads to reductions in physical and mental health, and quality of life [1], resulting in increased direct and indirect costs to the global economy [2]. Separate studies involving transfer of obese human fecal microbiome samples induced fat gain in naïve mice [5] and supplementation with Akkermansia muciniphila improved insulin sensitivity and reduced body weight in overweight and obese people [6], providing some evidence for a potential role of diet- and obesity-associated gut microbiota changes in adiposity and metabolic dysfunction. Weight loss through lifestyle intervention is an effective strategy for reducing obesity-related comorbidities [7] One such intervention is moderate exercise, a practical and sustainable approach for people with overweight and obesity [8]: while exercising at this intensity is unlikely to cause weight loss independent of caloric restriction, it confers cardiovascular and metabolic benefits, and assists with weight maintenance [9, 10]. Limited work has investigated whether treadmill exercise commenced following exposure to an obesogenic diet is sufficient to alter microbiome composition and metabolic health

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