title: Disease prevention--should we target obesity or sedentary lifestyle?
abstract: Obesity is a major health challenge facing the modern world. Some evidence points to obesity itself as the main driver of premature mortality. We propose that this view is oversimplified. For example, high levels of physical activity and cardiorespiratory fitness are associated with lower mortality, even in those who are overweight or obese. To address this issue, we combine epidemiological and physiological evidence in a new paradigm that integrates excess calorie intake, sedentary behavior, and a maladaptive response to stress. Human physiology is optimized to allow large distances to be covered on foot every day in order to find enough food to sustain brain metabolism. Furthermore, when the body is immobilized by an injury, it triggers efficient life-saving metabolic and inflammatory responses. Both these critical adaptations are, however, confounded by a sedentary lifestyle. The implications of these issues for clinical trial design and epidemiologic data analysis are discussed in this article.
authors.affiliation: Department of Cardiology, Centre Hospitalier Sud Francilien, 59 Boulevard Henri Dunant, 91108 Corbeil Essonnes Cedex, France. olivier.charansonney@orange.fr
authors.forename: Olivier L
authors.initials: OL
authors.lastname: Charansonney
authors.forename: Jean-Pierre
authors.initials: JP
authors.lastname: Després
mesh_terms: D000222:Adaptation, Physiological; D002318:Cardiovascular Diseases / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D004032:Diet / Q000009:adverse effects*; D002149:Energy Intake; D004734:Energy Metabolism; D019317:Evidence-Based Medicine; D006801:Humans; D018673:Nutrition Policy; D009752:Nutritional Status; D009765:Obesity / Q000209:etiology / Q000401:mortality / Q000503:physiopathology / Q000517:prevention & control*; D010809:Physical Fitness; D011634:Public Health; D012307:Risk Factors; D040242:Risk Reduction Behavior; D057185:Sedentary Behavior; D013312:Stress, Physiological