Obesity Pathogenesis: An Endocrine Society Scientific Statement

Abstract

Obesity is among the most common and costly chronic disorders worldwide. Estimates suggest that in the United States obesity affects one-third of adults, accounts for up to one-third of total mortality, is concentrated among lower income groups, and increasingly affects children as well as adults. A lack of effective options for long-term weight reduction magnifies the enormity of this problem; individuals who successfully complete behavioral and dietary weight-loss programs eventually regain most of the lost weight. We included evidence from basic science, clinical, and epidemiological literature to assess current knowledge regarding mechanisms underlying excess body-fat accumulation, the biological defense of excess fat mass, and the tendency for lost weight to be regained. A major area of emphasis is the science of energy homeostasis, the biological process that maintains weight stability by actively matching energy intake to energy expenditure over time. Growing evidence suggests that obesity is a disorder of the energy homeostasis system, rather than simply arising from the passive accumulation of excess weight. We need to elucidate the mechanisms underlying this "upward setting" or "resetting" of the defended level of body-fat mass, whether inherited or acquired. The ongoing study of how genetic, developmental, and environmental forces affect the energy homeostasis system will help us better understand these mechanisms and are therefore a major focus of this statement. The scientific goal is to elucidate obesity pathogenesis so as to better inform treatment, public policy, advocacy, and awareness of obesity in ways that ultimately diminish its public health and economic consequences.

Obesity and type 2 diabetes mellitus drive immune dysfunction, infection development, and sepsis mortality

“…It is defined as an excess of body‐fat mass, expressed as an elevated body mass index (BMI). The upper limit of a normal BMI in adults is 25 kg/m 2 whereas a BMI between 26 and 30 kg/m 2 is considered overweight, and a BMI > 30 kg/m 2 is classified as obese . In the United States, over 35% of adults and 17% of children are obese .…”

Pediatric Obesity: Influence on Drug Dosing and Therapeutics

“…Although recombinant human leptin analogue, a marketed product for leptin deficiency and generalized lipodystrophy, is contraindicated in general obesity, it was experimentally shown to prevent the regain of weight in previously obese individuals who lost weight . This finding adds credence to the theory that a pharmacologic agent could be developed to reset the defended body weight in obese people to a value that is closer to normal …”

“…There rarely is a single genetic cause of an underlying hormonal abnormality that leads to early weight gain in infants. A discussion of these topics is beyond the scope of this article, but can be found in a recent review . What follows is a brief overview of the pathophysiology of obesity to support an understanding of pharmacotherapy.…”

“…As a consequence, there is both stimulation of feeding and a reduction in energy expenditure. Together these processes defend a higher level of body fat and serve to restore body weight to its original set point . This physiologic response to weight loss likely explains the regain of weight following initial successful weight loss from most forms of obesity treatment.…”

“…It is hypothesized that the relative proportion of lipids in fat deposits, rather than the absolute amount, is the main determinant of metabolic risk. Different patterns of lipid partitioning may explain why some obese individuals develop comorbidities and others do not …”