PATHOGENESIS OF COMMON OBESITY

Obesity can result from increased energy intake, decreased energy expenditure, or a combination of the
two. Thus, identifying the etiology of obesity should involve measurements of both parameters. However, it is
difficult to perform direct and accurate measurements of energy intake in free-living individuals; and the
obese, in particular, often underreport intake. Measurements of chronic energy expenditure are possible

using doubly labeled water or metabolic chamber/rooms. In subjects at stable weight and body composition,
energy intake equals expenditure. Consequently, these techniques allow assessment of energy intake in
free-living individuals. The level of energy expenditure differs in established obesity, during periods of
weight gain or loss, and in the pre- or postobese state. Studies that fail to take note of this phenomenon are
not easily interpreted.
There is continued interest in the concept of a body weight "set point." This idea is supported by physiologic
mechanisms centered around a sensing system in adipose tissue that reflects fat stores and a receptor, or
"adipostat," that is in the hypothalamic centers. When fat stores are depleted, the adipostat signal is low,
and the hypothalamus responds by stimulating hunger and decreasing energy expenditure to conserve
energy. Conversely, when fat stores are abundant, the signal is increased, and the hypothalamus responds
by decreasing hunger and increasing energy expenditure. The recent discovery of the ob gene, and its
product leptin, and the db gene, whose product is the leptin receptor, provides important elements of a
molecular basis for this physiologic concept.