Etiopathogenesis of Obesity

Abstract

Obesity develops in an individual when energy intake exceeds energy expenditure over a prolonged period and the excess is stored as triglyceride, predominantly in adipose tissue. The rising prevalence of obesity worldwide is a major contributor to poor health, including diabetes, heart disease, and cancer. To understand the pathogenesis of obesity, it is important to understand the regulation of energy balance, which, although very tightly regulated, is subject to biological variation and easily overwhelmed by societal pressures and marketing influences. Control pathways for food intake and energy expenditure during as well as between meals include short-term mechanisms that operate from gastrointestinal tract to the central nervous system, as well as long-term signals that regulate the “set point” for body weight, which are dominated by leptin, an adipocyte-derived hormone. These pathways converge in the central nervous system, notably the hypothalamus, which plays a vital role in controlling food intake, energy expenditure, and other aspects of metabolism. Various genetic and environmental factors can influence these energy homeostasis mechanisms. Foods that are high in sugars and fat are potent rewards that promote eating even in the absence of absolute energy requirement, particularly in modern societies where food is available in abundance, and contribute to the obesity epidemic. Single gene disorders that result in obesity such as leptin deficiency and mutations in the pro-opiomelanocortin gene are rare but demonstrate the biological importance of these systems. Other etiological factors in some people may include drugs that increase appetite through central or peripheral mechanisms and structural damage to the hypothalamic areas involved in control of appetite. However, the recent increase in the prevalence of obesity is predominantly due to adverse environmental factors that are able to override these regulatory systems. These include widespread availability of high-energy foods, coupled with an unprecedented decline in levels of physical activity.