The paradox was first described in 1999 in overweight and obese people undergoing hemodialysis, and has subsequently been found in those with heart failure and peripheral artery disease (PAD).In people with heart failure, those with a BMI between 30.0 and 34.9 had lower mortality than those with a normal weight. This has been attributed to the fact that people often lose weight as they become progressively more ill. Similar findings have been made in other types of heart disease. People with class I obesity and heart disease do not have greater rates of further heart problems than people of normal weight who also have heart disease. In people with greater degrees of obesity, however, the risk of further cardiovascular events is increased. Even after cardiac bypass surgery, no increase in mortality is seen in the overweight and obese. One study found that the improved survival could be explained by the more aggressive treatment obese people receive after a cardiac event. Another study found that if one takes into account chronic obstructive pulmonary disease (COPD) in those with PAD, the benefit of obesity no longer exists. Causes
The "a calorie is a calorie" model of obesity posits a combination of excessive food energy intake and a lack of physical activity as the cause of most cases of obesity. A limited number of cases are due primarily to genetics, medical reasons, or psychiatric illness.
Pathophysiology
Two distinct but related processes are considered to be involved in the development of obesity: sustained positive energy balance (energy intake exceeding energy expenditure) and the resetting of the body weight "set point" at an increased value. The second process explains why finding effective obesity treatments has been difficult. While the underlying biology of this process still remains uncertain, research is beginning to clarify the mechanisms.At a biological level, there are many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until the leptin gene was discovered in 1994 by J. M. Friedmans laboratory. While leptin and ghrelin are produced peripherally, they control appetite through their actions on the central nervous system. In particular, they and other appetite-related hormones act on the hypothalamus, a region of the brain central to the regulation of food intake and energy expenditure. There are several circuits within the hypothalamus that contribute to its role in integrating appetite, the melanocortin pathway being the most well understood. The circuit begins with an area of the hypothalamus, the arcuate nucleus, that has outputs to the lateral hypothalamus (LH) and ventromedial hypothalamus (VMH), the brains feeding and satiety centers, respectively.The arcuate nucleus contains two distinct groups of neurons. The first group coexpresses neuropeptide Y (NPY) and agouti-related peptide (AgRP) and has stimulatory inputs to the LH and inhibitory inputs to the VMH.