Wheel running reduces high-fat diet intake, preference and mu-opioid agonist stimulated intake

Highlights

• Wheel running decreases high-fat diet intake after DAMGO injection.

• Wheel running decreases preference for previously preferred high-fat diet.

• Wheel running suppresses weight gain during high-fat diet exposure.

• Exercised and sedentary rats had similar reward gene expression profile.

Abstract

The ranges of mechanisms by which exercise affects energy balance remain unclear. One potential mechanism may be that exercise reduces intake and preference for highly palatable, energy dense fatty foods. The current study used a rodent wheel running model to determine whether and how physical activity affects HF diet intake/preference and reward signaling. Experiment 1 examined whether wheel running affected the ability of intracerebroventricular (ICV) μ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) to increase HF diet intake. Experiment 2 examined the effects of wheel running on the intake of and preference for a previously preferred HF diet. We also assessed the effects of wheel running and diet choice on mesolimbic dopaminergic and opioidergic gene expression. Experiment 1 revealed that wheel running decreased the ability of ICV DAMGO administration to stimulate HF diet intake. Experiment 2 showed that wheel running suppressed weight gain and reduced intake and preference for a previously preferred HF diet. Furthermore, the mesolimbic gene expression profile of wheel running rats was different from that of their sedentary paired-fed controls but similar to that of sedentary rats with large HF diet consumption. These data suggest that alterations in preference for palatable, energy dense foods play a role in the effects of exercise on energy homeostasis. The gene expression results also suggest that the hedonic effects of exercise may substitute for food reward to limit food intake and suppress weight gain.

Introduction

Reduced physical activity and unhealthy diet choices are predominant factors that contribute to the global obesity crisis [1], [2]. Physical activity has multiple beneficial effects on general health. Data from animal models and clinical studies have suggested that sufficient physical activity can improve cardiovascular function [3], glucose metabolism [4], [5], mood disorders [6], [7], and lead to healthy weight maintenance and weight loss [8], [9]. While regular physical exercise can sustain a healthy weight or a weight loss regimen, the range of mechanisms by which exercise contributes to the control of body weight remains unclear.

One potential mechanism is through reducing intake of and preference for highly palatable, energy dense foods. According to National Weight Control Registry of the USA, individuals who successfully maintain ≥30 lbs (13.6 kg) weight loss for over one year exercise persistently, e.g. an average weekly energy expenditure of 2853.6 kcal from physical activity. The data also indicate a negative relationship between physical activity and fat intake, i.e. the more exercise the less fat intake [10]. Nonetheless, the few studies on exercise and macronutrient intake in human subjects have not provided consistent results [11], [12]. The primary limitations of studies involving human subjects include the control of the amount and intensity of exercise between and within subjects and food intake assessment. Furthermore, considerable variation in daily food intake and energy expenditure in humans has been reported [13], [14]. The studies that have investigated the effects of exercise on food intake/selection, however, normally measured food intake of only a single meal each prior to and after exercise regimen. Taken together, the fact that no consistent conclusions can be drawn from those studies may reflect the difficulty of using human subjects to elucidate physiological interactions among exercise, appetite, and the multiple regulatory mechanisms controlling food intake. Thus, the current study applied a diet choice (high carbohydrate chow vs. high fat diet) protocol in a well-developed rat wheel running model to examine the effects of voluntary physical activity on high fat (HF) diet intake and preference.

Previous studies have demonstrated that infusion of a μ opioid receptor agonist D-Ala2, NMe-Phe4, Glyol5-enkephalin (DAMGO) into the brain increases HF diet intake and preference [15], [16]. Furthermore, opioid agonists and antagonists have been reported to enhance or attenuate wheel running activity and the effects produced by it [17], [18], [19]. Despite these effects, no study has examined how highly palatable food and physical activity interact to alter μ opioid receptor stimulated behaviors and related gene expression. This study examined whether and how exercise affects HF diet preference from two perspectives. Experiment 1 tested whether wheel running alters DAMGO induced increases in HF diet intake/preference. Because μ opioid receptors undergo several post-translational modifications [20], using a selective μ opioid receptor agonist, such as DAMGO, will allow us to accurately assess the interaction between wheel running and highly palatable food intake on μ opioid receptor stimulated behaviors. Multiple studies have reported that wheel running is rewarding [21], [22], [23] and may alter the drive for other rewards, e.g. drugs of abuse [24], [25] and palatable food [26], [27]. Thus, Experiment 2 examined whether wheel running reduces preference for a previously preferred HF diet. Both the dopaminergic and opioid systems mediate the intensity/amount [17], [19], [28], [29], [30] as well as the rewarding effects of wheel running in rodents [18], [22], [31], [32]. Thus, Experiment 2 also determined whether wheel running alters the mRNA expression of dopaminergic and opioidergic genes in reward pathways.