Why some of us get fat and what we can do about it.

There is a widespread obesity epidemic in the developed world which is having an adverse impact on the health of affected individuals. Many of the afflicted have a genetic predisposition to become obese. These individuals become obese when they over consume highly palatable, calorically dense foods which are readily available at low cost. Once obesity occurs, fewer than 10% of affected individuals can sustain significant weight loss permanently. The hypothesis of this review is that some obesity-prone individuals have an inborn reduction in their ability to sense and respond to inhibitory signals from adipose stores and other organs which should limit their intake of energy when it exceeds their metabolic needs. Furthermore, the physiological processes which drive all of us to seek and ingest food and limit energy expenditure during periods of negative energy balance provide an irresistible drive to regain lost adipose stores in weight-reduced obese individuals. For this reason, prevention of obesity and the identification factors which promote the development of neural pathways which enhance the negative feedback signals from the periphery should be a major focus of ongoing research in this field.