Decades of research have unfortunately failed to prevent the continuous rise of chronic diseases prevalence. Understanding modern health problems cannot be achieved without an evolutionary and ecological approach. The evolutionary approach recognizes the biological constraints imposed by the fact that most of human evolution took place when our ancestors were hunter-gatherers. Indeed, 95% of human biology, and probably human behavior, was naturally selected at the time of the emergence of the modern human genome with the appearance of Homo sapiens about 200,000 years ago. Since then, our genetic heritage, although in constant evolution, has undergone few mutations and has remained relatively stable in terms of our physiology. Although genes play a role in regulating human metabolism through individual susceptibility, they alone cannot explain the recent evolution of chronic diseases, including obesity, insulin resistance, type 2 diabetes, cardiovascular and coronary heart disease, dyslipidemia, non-alcoholic fatty liver disease, cancers, etc., whose prevalence keeps increasing. A potential reason for our inability to prevent obesity and the associated chronic diseases is that the complex interactions between the biological, behavioral, and socio-ecological factors as well as their respective role in the regulation of body weight is still not well understood. The epidemiological transition model summarizes the changes in nutrition, physical activity and culture/lifestyle that initiated the onset of obesity in Westernized countries. Studying in real-time populations from pre-industrialized countries where the epidemiological transition is ongoing is an ideal paradigm to determine the causes of the obesity epidemic. The Fulani people living in Senegal offer the exceptional opportunity to address this question. They are composed of sub-populations who are at different stages of the epidemiological transition, i.e. those living in urban environment (Dakar) and those living in rural environment (Ferlo) either in villages with access to diverse food and a borehole for water, in camps at 10-15km of a borehole, or in camps where a borehole will be built in 2020, which will dramatically accelerate the impact of the transition. Those in the Ferlo are nomadic people, known to leave for long months in transhumance, and are still in the process of settling down. This population offers a unique opportunity to understand the impact of major changes in lifestyles, diet and physical activity induced by urbanization and epidemiological transition on weight regulation.   In this presentation, we will introduce the physical activity transition and the associated impact on human cardiometabolic health. We will present our first data on the daily pattern of physical activity in the Fulanis living in contrasted environments. We will then present recent evidence from population, cross-sectional and intervention studies showing the effects of large volumes of sedentary behaviors and low levels of physical inactivity on metabolic health outcomes. Finally, we will provide with information about potential strategies to combat the adverse health effects of sedentary behaviors and physical inactivity.