**2. The Effect of Exercise on Weight Management and Inflammation**

Exercise is regularly prescribed as a first-line treatment in preventing type 2 diabetes, coronary artery disease (CAD), and non-alcoholic fatty liver disease (NAFLD) [11–13]. It has strong therapeutic effects that usually meet or exceed expected improvements in metabolic function from pharmaceutical treatment [14]. Exercise training triggers significant metabolic adaptations that improve cardiorespiratory fitness, promoting greater capillary density and increases in HDL synthesis to protect from CAD [14,15]. Exercise also enhances glucose uptake through elevating translocation of GLUT4 in skeletal muscle and by increasing IRS-1 phosphorylation, an insulin receptor substrate that improves insulin sensitivity [16,17]. Therefore, exercise can be a reliable first-line and preventative therapeutic for type II diabetes by decreasing blood glucose [18] and CAD by reducing atherosclerotic plaque buildup and subsequent risk of stroke and myocardial infarction [19].

Although exercise training can improve blood glucose control, insulin sensitivity, and other aspects of metabolic syndrome without weight loss, these benefits are substantially greater when significant weight loss occurs [20–23]. Indeed, the American College of Sports Medicine issued separate recommendations to maintain health [24] or support weight loss through exercise [25]. Exercise is also one of the primary recommendations of the Diabetes Prevention Program (DPP) and a pivotal component to the classic Look AHEAD trial primarily due to the role that exercise is thought to play in weight loss and weight management [26,27]. Unfortunately, weight loss from exercise is often suboptimal due to compensatory mechanisms that resist the maintenance of an energy deficit [8–10]. For instance, an individual may exercise to expend 3000 kcal per week for ten weeks through exercise to expend a total of 30,000 kcal. However, this individual rarely loses 30,000 kcal of body mass. By comparing changes in bodily energy stores with the amount of total energy expended through exercise, we have demonstrated this compensatory response to equate to roughly 1000 kcal per week during a 12-week exercise intervention, and that energy expenditures of greater than 2700 kcal per week are needed to achieve significant weight loss after 12 weeks. [28,29]. Others have reported that greater amounts of exercise can evoke a proportionally greater compensatory response [30], potentially explaining why exercise interventions with large differences in daily and weekly exercise energy expenditures can promote similar weight loss [30–33]. Because of this, many have turned to various EE's to improve both weight loss and metabolic health outcomes with exercise. We will discuss some specific studies on EE's below and how they might impact exercise-induced ROS and inflammation.
