Behavioral Mechanism of Energy Compensation With Exercise
Behavioral Mechanism of Energy Compensation With Exercise
Over 70% of Americans are either overweight or obese, putting them at risk for many chronic
 diseases including diabetes. Exercise is commonly used as a weight loss and weight loss
 maintenance strategy. However, exercise-induced weight loss is often much less than expected
 as individuals compensate for a large portion of the energy expended through exercise,
 resisting maintenance of the negative energy balance needed for weight loss. Our prior
 research, in agreement with others, point to increases in energy intake as the primary
 compensatory response when exercising for weight loss; however, mechanisms promoting this
 behavior have yet to be fully elucidated. With obesity and diabetes prevalence continually
 rising, innovative research is needed to identify novel mechanisms promoting energy
 compensation with exercise. The long-term goal of this proposal is to reduce the incidence
 and improve the outcomes of obesity-related diseases by developing interventions that will
 attenuate compensation for the energy expended through exercise and thus improve initial
 weight loss and weight loss maintenance. The present proposal will take the necessary first
 steps towards our long-term goal by identifying novel mechanisms promoting energy intake when
 exercising for weight loss.

 One's reinforcing value of food, attentional bias and inhibitory control for food cues play
 an important role in feeding behaviors, independent of hunger. These behaviors are largely a
 product of the central dopamine reward system, which is also in play with exercise behavior.
 This provides mechanistic support for our central hypothesis, that exercise evokes increases
 in food reinforcement, attentional bias, and lowers inhibitory control for food cues to
 promote greater energy intake in effort to maintain energy homeostasis. The rationale for
 this project is by elucidating the mechanisms mediating energy compensation, future
 interventions can be designed that attenuate this response to improve the utility of exercise
 as a weight loss intervention to prevent and manage T2DM. The overall objective of the
 current proposal is to demonstrate an acute bout of exercise alters food reinforcement,
 attentional bias and inhibitory control for food cues. Upon completion, we will have a
 greater understanding of the mechanisms underpinning compensatory increases in energy intake
 when exercising. These findings will pave the way for future clinical trials testing this
 hypothesis in the context of a long-term exercise intervention. This contribution is
 significant, as the identification of novel mechanisms influencing energy compensation with
 exercise is needed to provide strong support for the development of novel, evidence-based
 interventions to attenuate this compensatory response to exercise, improving its efficacy for
 weight control and chronic disease management.
Over 70% of adults in the US are overweight or obese putting them at risk for a multitude of
 comorbidities including cardiovascular disease, hypertension, diabetes, dyslipidemia,
 metabolic syndrome, and certain cancers. Greater mortality rates with obesity have estimates
 of life expectancy reduced by 6-7 years with up to 300,000 deaths attributed to obesity
 annually in the US. Obesity treatment has therefore emerged as a prime focus of health care.

 Increasing physical activity and energy expenditure is a universal recommendation for weight
 control, with exercise becoming the most prevalent, economical, and health-promoting
 treatment option for obesity.

 Unfortunately, weight loss from an exercise program is often disappointing, and greater
 amounts of exercise may not always promote additional weight loss. An increasing body of
 evidence indicates individuals' concerted efforts to achieve weight loss through exercise are
 stymied by a coordinated set of compensatory responses working to maintain energy balance,
 conserving energy to ensure the energetic needs of vital organs are met. The primary
 compensatory response working to maintain energy homeostasis and thus opposing weight loss
 from an exercise-induced energy deficit is an increased drive for greater energy intake. This
 is often independent of hunger, as single bouts of exercise typically do not result in
 changes in appetite, food intake, or appetite- regulating hormones, while long-term exercise
 can actually improve the satiety response to a meal. The motivational aspects of eating,
 termed the reinforcing value of food, is a strong predictor of body weight and energy intake
 independent of hunger, although not previously studied as an important factor in energy
 compensation with exercise. Food reinforcement is developed by instigating a greater
 attentional processing towards food, termed attentional bias. These behavioral constructs are
 controlled by the central dopamine system, which mediates the rewarding aspects of
 reinforcing behaviors (such as eating) and is a more powerful driver of behavior than
 affective responses. Overeating occurs when the motivational wanting of food exceeds the
 capacity of inhibitory control for eating. As such, individuals with lower inhibitory control
 are more susceptible to the reinforcing aspects of food, and more likely to over-consume
 highly reinforcing, energy dense foods. With additional evidence eating and exercise
 behaviors share similar neuro-behavioral pathways possibly explaining why exercise can
 promote feeding in animal models, it would be of great interest to determine the influence
 exercise may have on food reinforcement, attentional bias, and inhibitory control for food
 cues in humans.

 Our long-term goal is to reduce the incidence and improve the outcomes of obesity by
 developing interventions to attenuate compensation for the energy expended through exercise
 thereby improving exercise as a weight loss and weight loss maintenance strategy. The overall
 objectives of the current proposal are to 1) evaluate whether an acute bout of exercise
 alters food reinforcement, attentional bias and inhibitory control for food cues, and 2)
 assess a potential sex effect in this response. Our central hypothesis is that exercise
 training will evoke greater food reinforcement and attentional bias for food cues while
 reducing inhibitory control as a mechanism to promote greater energy intake in effort to
 maintain energy homeostasis. Our hypothesis has been formulated based on our preliminary data
 demonstrating a large (~1,000 kcal per week) compensatory response to a 12-week exercise
 intervention that could not be explained by changes in resting energy expenditure, physical
 activity outside the exercise intervention, or hormonal mediators of appetite. This
 compensatory response was observed across two different studies using various exercise doses,
 indicating a remarkable consistency in this compensatory response. Previous research in
 animal models have demonstrated exercise facilitates eating, with evidence of shared
 neuro-behavioral pathways between eating and exercise reward that may explain this
 connection. These behavioral constructs influencing energy intake have not been considered as
 mechanisms for energy compensation and likely contribute to the unexplained compensatory
 response we have previously observed. The rationale for this project is that with greater
 knowledge of the mechanisms behind energy compensation, future interventions may be designed
 that attenuate this response to improve exercise's utility as a weight loss strategy. To
 achieve the overall objectives, we will pursue the following specific aim and exploratory aim
 in obese, sedentary individuals, the population in greatest need for effective weight loss
 treatment: Specific Aim: Demonstrate changes in food reinforcement, attentional bias and
 inhibitory control for food cues after an acute bout of exercise. Based on our preliminary
 data and previous literature demonstrating exercise may increase food reward, our working
 hypothesis is an acute bout of exercise will cause food to be more reinforcing, increase
 attentional bias for food cues, and decrease inhibitory control for food cues.

 Exploratory Aim: We will explore whether sex moderates these responses. Others have
 demonstrated sex differences in food reinforcement, although the role sex plays in this
 response to exercise is unknown.

 At the completion of the proposed research, the expected outcomes are to have identified
 novel mechanisms that contribute to energy compensation during an exercise program. These
 results will have a sustained impact as they will provide a strong evidence-based proof of
 principle for development of novel interventions that attenuate the compensatory response to
 exercise, improving its efficacy for weight control.

 Significance Importance of the Problem to Be Addressed. Greater than 70% of US adults are
 either obese (BMI > 30) or overweight (BMI 25-29.9). Poor dietary habits and physical
 inactivity are the top causes for this epidemic. Over 90% of US adults fail to meet physical
 activity recommendations when assessed objectively, while over 95% fail to meet
 recommendations for solid fat and added sugar intake [5]. The impact of obesity on society is
 realized in its associated comorbidities, including cardiovascular disease, hypertension,
 diabetes, dyslipidemia, metabolic syndrome, gallstones, osteoarthritis, sleep apnea,
 premature death, and many cancers such as breast, liver, and colon. The economic impact of
 obesity is startling, with annual health care expenditures between $92-117 billion, making
 obesity among the most expensive health problems in the US [8].

 The continually escalating obesity epidemic suggests the majority of individuals are unable
 to meet their weight loss needs. Evolutionarily conserved mechanisms that defend against a
 negative energy balance are, in part, to blame [9]. These mechanisms include metabolic and
 behavioral responses to an energy deficit that function to conserve energy by either reducing
 energy expenditure or promoting energy intake. Metabolic adaptations reduce resting and
 non-resting energy expenditure to account for approximately 120 kcal/day through mechanisms
 related to thyroid function, skeletal muscle glucose oxidation, and sympathetic nervous
 system activity. Behavioral responses to an energy deficit, on the other hand, can account
 for far more than 120 kcal/day and include increases in energy intake and decreases in
 physical activity. Many agree the most impactful compensatory response working to resist an
 exercise-induced energy deficit is increases in energy intake, as the rate of energy intake
 far exceeds the rate of energy expenditure. The mechanisms underlying this compensatory
 response are poorly understood.

 Exercise is the most common weight loss strategy with a prevalence rate of 65% among those
 attempting to decrease body weight. Indeed, most people have the capacity to increase their
 energy expenditure to promote negative energy balance whereas, depending on an individual's
 aerobic fitness, exercise intensities can be maintained for prolonged periods at 2- to
 16-fold above resting rates of energy expenditure. As such, 250 to 2500 kcal can be expended
 during a single exercise session resulting in an acute energy deficit that can be repeated
 across days. This has prompted the American College of Sports Medicine to issue separate
 recommendations to either maintain health or support weight loss through exercise. Exercise
 is also one of the primary components of the Diabetes Prevention Program (DPP) and a key
 aspect to the classic Look AHEAD trial primarily due to the role exercise is believed to play
 in weight loss and weight loss maintenance. However, reductions in body weight from exercise
 training are often less than expected due to the compensatory responses working to maintain
 energy balance noted above.

 Our preliminary data, in agreement with others, point to increases in energy intake being the
 primary compensatory response to an energy deficit induced by exercise. Other purported
 compensatory responses include decreases in resting energy expenditure (REE), improved
 skeletal muscle work efficiency, and decreased habitual physical activity outside the
 exercise program [9]. We have twice demonstrated non-significant changes in REE, total energy
 expenditure, and habitual physical activity outside the exercise intervention despite a
 compensatory response of approximately 1,000 kcal/week. This supports the premise that
 increases in energy intake are largely responsible for this compensatory response to
 exercise, although the mechanisms behind this response remain unknown. Identifying the
 mechanisms for this compensatory response is the necessary first step in developing
 interventions that aim to attenuate the compensatory increases in energy intake that
 accompany an exercise program. Such interventions would vastly improve exercise as a weight
 control strategy.

 An often-studied mechanism responsible for greater energy intake with exercise is increased
 hunger, assessed by hormonal mediators of appetite, lab-based food intake, and hunger/satiety
 scales [28-32]. In particular, elevated concentrations of the orexigenic hormone ghrelin and
 reductions in satiety-inducing signals such as peptide YY (PYY), glucagon-like peptide one
 (GLP-1), pancreatic polypeptide (PP), cholecystokinin (CCK), and leptin may all be altered to
 promote greater energy intake when participating in exercise training. However, single bouts
 of exercise typically do not result in the expected compensatory increases in appetite.
 Conversely, greater perceptions of fullness persist 24 hours after exercise, and long-term
 exercise can actually improve the satiety response to a meal. Thus, other mechanisms are
 likely involved, necessitating novel and innovative research to better understand the
 mechanisms behind this compensatory response to exercise.

 Central dopamine (DA) systems are essential for experiencing reward (i.e. DA hypothesis of
 reward), where adaptations in this system were originally proposed to explain drug addiction.
 Interestingly, both exercise and eating behaviors are largely driven by this central DA
 system as genetic polymorphisms that control DA uptake and transport have been linked to
 exercise and eating reward. This offers the possibility for a neuro-behavioral cross-talk
 between these behaviors, explaining why individuals who exercise for weight loss often have
 distorted portion control, seek rewards from exercising in the form of food, and derive
 greater pleasure from high-fat, high-sugar, energy-dense food independent of hunger. There is
 evidence of such direct cross-talk between eating and exercise reward in rats, where wheel
 running that produces a low-level dopaminergic response facilitates eating. In humans,
 evidence points to exercise promoting a greater wanting to eat among individuals who
 overcompensate (eat more energy than they expend) due to exercise potentially having a
 sensitizing action that enhances food reward to increase energy intake. A similar neuro-
 behavioral cross-talk between the reinforcing effects of different drugs is also known,
 specifically involving endogenous opioid and cannabinoid systems, whereas administration of
 one increases the reinforcing value of the other. The possibility for exercise to increase
 the rewarding aspects of food and thus energy intake is therefore a probable scenario,
 although this has not been fully evaluated in humans.

 The rewarding aspects of eating are important volitional behavioral responses influencing
 energy intake, assessed by defining one's reinforcing value of food. Food reinforcement is a
 measure of how much an individual wants to engage in a particular eating behavior, as someone
 who finds food highly reinforcing "wants" food to a greater degree. Food reinforcement is a
 more robust predictor of food intake than the hedonic value (i.e., liking) and is a strong
 predictor of body weight. Food deprivation resulting in energy deficits increases food
 reinforcement, and thus possible that an exercise-induced energy deficit will increase food
 reinforcement as a mechanism to promote feeding behavior and maintain energy balance. No
 study has been conducted characterizing and testing this behavioral response to exercise in
 humans.

 Increasing the reinforcing value of a behavior is accomplished through "incentive
 sensitization". Incentive sensitization is a behavioral process where repeated exposures
 increase the salience of a stimulus within the environment to produce an attentional bias.
 This produces neuroadaptations that increase the motivating or reinforcing value of the
 behavior. Attentional bias towards food cues is therefore an additionally relevant and
 important construct to consider when elucidating the motivational implications of eating.
 Increased attentional bias for food cues predicts the tendency to overeat and weight status,
 with obese individuals having greater attentional bias towards food cues, especially for
 energy-dense palatable foods. Overeating occurs when motivational wanting of food exceeds the
 capacity for inhibitory control for eating, as such, a heightened awareness/attentional bias
 of food or food reinforcement may lead to overeating in those with reduced inhibitory
 control. This puts individuals with poor inhibitory control at a greater susceptibility to
 food's rewarding effects, increasing energy intake and promoting weight gain. This
 association has not been assessed alongside exercise, and exercise-mediated increases in food
 reinforcement and attentional bias may follow different patterns than previously observed
 cross-sectional data, which has used primarily sedentary individuals. Based on our most
 recent preliminary data demonstrating 38/44 participants demonstrated some form of positive
 compensation after a 12-week exercise intervention, exercise may either lower inhibitory
 control as an additional mechanism to promote energy intake, or food reinforcement and
 attentional bias for food cues may be increased greater than what can be mitigated by one's
 inhibitory control.

 Significance of the Proposed Research Contribution The expected contribution is an enhanced
 understanding of the mechanisms underpinning energy compensation to exercise. This
 contribution will be significant as this will provide the necessary information to develop
 future trials and treatments to facilitate more successful and sustained weight loss over
 time from an exercise program, reducing rates of obesity and related complications. These
 results are intended to both improve scientific knowledge and directly inform clinical
 practice as it pertains to obesity treatment and prevention. Currently, behavioral
 compensatory responses are not commonly considered a modifiable barrier to exercise-induced
 weight loss, possibly due to the unknown nature of the mechanisms behind them or how they may
 be modified. Novel mechanisms must be identified as it appears research on traditional
 mediators of energy intake (hunger/satiety) do not provide a definitive conclusion.
 Identifying the role food reinforcement, attentional bias and inhibitory control for food
 cues play in the exercise-induced increases in energy intake will lead to future research
 targeting these mechanisms to improve the effectiveness of exercise for weight control.

 Innovation The status quo, as it pertains to obesity treatment, is ineffective with the
 continually escalating obesity epidemic serving as evidence. Exercise programs for obesity
 treatment often do not consider energy compensation as an integral aspect of weight loss. Our
 preliminary data and others have confirmed the compensatory response to exercise and that
 greater energy intake is the largest source of compensation. However, little is known of the
 mechanisms that mediate this compensatory response.

 The proposed research is innovative because it challenges current obesity research paradigms
 by focusing on the underlying mechanisms of energy compensation with exercise. Specifically,
 food reinforcement, attentional bias and inhibitory control for food cues are volitional
 behavioral responses that will be evaluated as important mediators in the compensatory
 response to exercise. These constructs are strong predictors of weight status and energy
 intake but have yet to be evaluated in the context of exercise. With evidence that exercise
 can influence the neuro-behavioral processes underlying food reinforcement, attentional bias
 and inhibitory control for food cues, the present investigation's hypotheses are not only
 highly novel but also highly probable. The investigative team of Dr. Kyle Flack (PI, an
 experienced nutritionist, exercise and behavioral physiologist) coupled with Dr. Craig R.
 Rush (Co-I, an experienced behavioral scientist with expertise in attentional bias and
 inhibitory control) is an additionally novel aspect and uniquely suited to carry out this
 proposal. Successful completion will open new horizons for obesity treatment, including novel
 interventions that focus on attenuating exercise-induced alterations in food reinforcement,
 attentional bias and inhibitory control for food cues.

 Approach Preliminary Data. Our preliminary studies on energy compensation with exercise have
 indicated non-significant changes in resting energy expenditure (kcal/24 hrs) and
 non-exercise physical activity despite an approximate 1,000 kcal per week compensatory
 response regardless of exercise energy expenditure (1500 vs. 3000 kcal/week) or exercise
 frequency (2 vs 6 sessions/week). This demonstrates the overall magnitude of energy
 compensation sedentary individuals exhibit when engaging in a 12-week exercise intervention
 that did not include dietary restriction. Importantly, the lack of pre-post changes in REE
 and non-exercise physical activity indicate changes in energy intake are the primarily
 responsible for this 1,000 kcal/week compensatory response. Additionally, changes in the
 hormonal mediators of appetite and satiety were not related to this compensatory response.
 For this reason, research focused on identifying novel mechanisms promoting increases in
 energy intake when exercising for weight loss is needed to develop interventions that work to
 mitigate this response and thus improve weight loss outcomes. The reinforcing value of food,
 attentional bias, and inhibitory control for food cues are behavioral constructs known to
 play a large role in eating behaviors and weight status. As we have noted, there is strong
 rational for investigating how these behavioral constructs are uniquely influenced by
 exercise, centered on the shared neuro-behavioral pathways within the DA reward system that
 may link exercise and eating behavior. This has been observed in rodents, where exercise that
 causes a dopaminergic response promotes eating, but has yet to be fully investigated in
 humans.

 Research Design. This pilot study will use a counterbalanced cross-over design to assess the
 acute effects of a single bout of exercise and a single bout of sedentary activity on food
 reinforcement, attentional bias and inhibitory control for food cues among overweight to
 obese, sedentary adults (n=60, 30 males, 30 females). Differences in food reinforcement,
 attentional bias and inhibitory control for food cues will be determined between conditions
 (bout of exercise vs bout of sedentary activity), time (before exercise vs. after) and sex
 (male vs. female). This will allow us to determine how exercise influences the behavioral
 mediators of energy intake compared to both a non-exercise control condition and a
 pre-exercise condition.

 Setting. All study activities will be conducted at the University of Kentucky (UK) Center for
 Clinical and Translational Science (CCTS), Laboratory of Human Behavioral Pharmacology
 (LHBP), and the Nutrition Assessment Laboratory (NAL), all located in Lexington Kentucky, on
 or surrounding the UK campus.

 Participants, recruitment, and screening. Recruitment will include 72 community-dwelling
 overweight to obese (BMI 25-45 kg/m2) men (n=36) and women (n=36) aged 18-45 years who are
 not currently engaged in exercise or weight loss activities, nor have lost or gained over 5%
 of their current bodyweight in the previous 12 months. Eligible participants will also be (1)
 free of any cardiac, pulmonary, or metabolic health conditions, (2) able to safely engage in
 exercise, (3) not taking any medications or dietary supplements which may influence energy
 expenditure or intake and (4) have not been diagnosed with an eating disorder, clinical
 depression, or an anxiety disorder and (5) engage in less than 150 minutes of moderate to
 vigorous physical activity per week (assessed via accelerometry at baseline). Female
 participants must additionally be premenopausal and not pregnant or nursing. Ability to
 safely participate in exercise will be determined using a health history and Physical
 Activity Readiness Questionnaire (PAR-Q+) and reviewed by the study physician. Participants
 will be recruited from the greater Lexington, KY area using a combination of print and online
 media methods. Interested individuals will be screened for basic inclusion criteria (age,
 activity level, BMI) and, if deemed initially eligible, invited for a screening visit to
 further assess eligibility. Based on our previous 12-week exercise intervention performed at
 the University of Kentucky we will expect an overall retention rate of 85%, leaving an n=60
 completing both assessment visits.

 Procedures Visit 1 (week 1). The Study Coordinator will meet with each participant for a
 30-minute orientation session. At this time, participants will have the study explained,
 questions answered, complete the necessary screening questionnaires (health history, PAR-Q+),
 complete an Accu-Check blood glucose test, and, if deemed eligible and interested, sign the
 informed consent. Upon enrollment, participants will also complete a food frequency
 questionnaire (DHQ-3), be assessed for body composition (BodPod), and have waist
 circumference measured. Participants will also be provided an ActiGraph accelerometer to
 objectively assess physical activity for the next seven days and scheduled for Visit 2 at
 least eight days later. Participants will be instructed not to purposely change dietary
 behaviors while enrolled in the study (i.e. start to diet).

 Visits 2 and 3 (week 2 and 3). On the day of Visit 2, participants will record the specific
 foods, quantities, and time of day they consumed them prior to their testing visit.
 Participants will be instructed to eat the same foods at the same time of day prior to Visit
 3 as they did prior to Visit 2. Visit 2 and 3 will be scheduled at the same time of day on
 the same day of the week where participants will be able to practice "usual" dietary
 behaviors, i.e. not on a holiday or a special occasion. Upon arriving to the LHBP exactly
 four hours post-prandial in the afternoon, participants will complete assessments for food
 reinforcement, attentional bias and inhibitory control for food cues before and twice after
 an acute bout of either exercise or sedentary activity, with one visit featuring exercise and
 the other visit featuring a sedentary activity. The order of the visits will be
 counterbalanced. Visual analog scales (VAS) will be performed for hunger and exercise
 enjoyment prior to each set of assessments. For female participants, these visits will occur
 while in the follicular phase, which will be assessed by a mensural cycle questionnaire.
 Participants will wear the accelerometer to record physical activity during the washout
 period between assessment visits and be instructed to remain sedentary.

 Acute Bout of Exercise. Participants will complete assessments of food reinforcement,
 attentional bias and inhibitory control before and after an acute bout of exercise during
 Visit 2 or visit 3 (depending on counterbalanced order). Participants will be provided a
 Polar A-300 heart rate monitor with smart-cal™ technology that factors the individual's sex,
 age, weight, activity level, and heart rate to produce an estimate of total energy in
 kilocalories (kcal) expended during the exercise session, with kcal expended displayed in
 real- time. Participants will engage in exercise on an elliptical ergometer (Octane Fitness
 ZR8) for the amount of time it takes them to expend 500 kcal under supervision of a
 researcher in the laboratory. Participants will exercise at a self-selected intensity of at
 least 65% heart rate reserve (HRR), an intensity commonly prescribed for sedentary
 individuals beginning an exercise program. Based on previous studies conducted in our lab,
 500 kcal of energy expenditure is attainable for even the most sedentary individual with
 exercise sessions lasting between 30 and 70 minutes depending on body mass and intensity of
 exercise. Prescribing the exercise bout on energy expenditure rather than duration or
 intensity will standardize the amount of total work being done across all participants. While
 both the intensity and duration of the exercise could be controlled, due to differences in
 body mass of the participants, either the exercise time or total work would still vary. An
 energy expenditure of 500 kcal is specifically used to ensure the exercise bout is of
 sufficient volume (intensity * time) to produce weight loss if included in a long-term
 program and to elicit a dopaminergic response. Participants will be permitted to drink 0.5 l
 of water during and after the exercise bout. Participants will take a brief 15-minute rest
 after completing the exercise session before repeating assessments for food reinforcement,
 attentional bias and inhibitory control for food cues (post exercise assessment 1).
 Participants will repeat these assessments 60 minutes after cession of the exercise and
 sedentary activity bout (post exercise assessment 2).

 Acute Bout of Sedentary Activity. Participants will complete assessments of food
 reinforcement, attentional bias and inhibitory control before and after an acute bout of
 sedentary activity (TV). Participants will watch TV for 60 minutes, choosing from a variety
 of television sitcoms (DVD) void of commercial advertisements that may feature food.
 Participants will have access to 0.5 l of drinking water during and after the test bout of TV
 viewing.

 Statistical Analysis Linear mixed models will be fit with exercise and time as random effects
 to account for repeated measures and sex as a fixed effect. Response variables will be
 transformed if appropriate. With binary explanatory variables, an unstructured covariance
 matrix for the random effects will be assumed, but alternatives will be considered if needed.
 VAS scale ratings of hunger/satiety and exercise enjoyment will be assessed and included for
 adjustment as necessary. Power analysis: Because of our three response variables, we will use
 a Bonferroni corrected type I error rate of 0.05/3 = 0.017 for our regression models. In a
 linear regression model with n = 60, 30 males and 30 females, counterbalanced to start with
 and without exercise and then crossing over to the other treatment, we will have 80% power to
 detect models with R squared of 20.4% or more (nQuery 8.5.1). Our mixed models will improve
 model fit and decrease variance estimates compared with linear regression, thus increasing
 power or decreasing R squared type measures that can be detected.

 Exploratory Aim: By including sex as a fixed effect in our linear mixed model approach, our
 study is designed and powered to determine the role of sex may play in the hypothesized
 exercise-induced changes to the behavioral mediators of energy intake assessed. Previous work
 in animals have identified a sex effect in eating reward/reinforcement where females have
 greater neurobehavioral drive to consume food. It is unknown, however, if sex may play a role
 in the response to exercise, warranting this exploration.
Inclusion Criteria:

 -  overweight to obese (BMI 25-45 kg/m2)

 -  not currently engaged in exercise or weight loss activities

 -  free of any cardiac, pulmonary, or metabolic health conditions

 -  able to safely engage in exercise

 -  female participants must be premenopausal and not pregnant or nursing.

 Exclusion Criteria:

 -  Lost or gained over 5% of their current bodyweight in the previous 12 months.

 -  taking any medications or dietary supplements which may influence energy expenditure
 or intake

 -  have not been diagnosed with an eating disorder, clinical depression, or an anxiety
 disorder

 -  engage in less than 150 minutes of moderate to vigorous physical activity per week
 (assessed via accelerometry at baseline)