Overview of clinical perspectives and mechanisms of obesity


One only has to open the newspaper or turn on the radio to hear about the epidemic of obesity in America. Not only does obesity exact a heavy toll on the population's health, but the medical costs associated with obesity, especially those related to treatment for type II diabetes and cardiovascular disease, are astronomical. The American Medical Association now estimates that the expense to society of treating obesity-associated diseases, particularly diabetes, now exceeds that of smoking-related diseases (Schwimmer et al., 2003). Even the aviation industry has recently increased its average per-passenger weight estimate by 10 pounds, in order to maintain air safety in the face of the ever-increasing waistline (Phillips, 2003).

The existence of adipose tissue as a specialized organ reflects the needs developed by organisms over time to cope with irregular and unpredictable supplies of nutrients. These needs became especially acute in the omnivorous mammals and were probably a key survival feature. In Homo sapiens, complex societal rituals developed that revolved around shared meals, and social status was assessed by the acquisition of social dominance. However, in more recent times, particularly in industrialized societies over the last 40 years, there has been more emphasis from a popular culture and fashion ideal to possess the least amount of body fat. Similarly, in the medical community there is also a greater emphasis on a leaner physique because of the growing alarm over the epidemic of adults and even children who are overweight or obese. The most recent statements from the Surgeon General of the United States and the World Health Organization (WHO) emphasize the need for the general public to lose weight (specifically, to reduce the percentage of body fat) because of the established associations between excess body fat and increased risk for a host of serious medical complications (Mokdad et al., 1999, 2003). An undeniable link connects excess body fat and the development of type II diabetes and cardiovascular disease, to name only two (Fig. 1). Therefore, not surprisingly, our country has seen trends toward obesity and the incidence of diabetes escalate in parallel over the past 20 years (Mokdad et al., 2000). Of concern, however, is the fact that most Americans do not perceive that they are overweight, which has made it difficult to get the message across that one of the preventive strategies that we must incorporate is a reduction in the size of food portions.

Figure 1.

Why do we care about obesity?

Although the process by which obesity promotes the development of diabetes would seem straightforward, the biochemical mechanisms that result from increased body fat remain unclear. Extensive study, however, has created general agreement that a greater amount of body fat causes a correspondingly greater flux of stored fatty acids into and out of the body's various tissues. It is also recognized that extreme deficiencies in body fat, such as in lipodystrophy, can be equally as detrimental in terms of diabetes risk as having too much fat (Reitman et al., 2000). The occurrence of lipodystrophy and its associated metabolic complications is growing substantially in a segment of the population, i.e., those infected with human immunodeficiency virus and receiving protease-inhibitor therapy (Carr and Cooper, 1998; Mallon et al., 2001, 2002). It is therefore important to understand the development and metabolic functions of adipose tissue and how these processes are regulated.

Until the 1990s, adipose tissue had been largely considered an inert storage depot for excess metabolic fuel. Accumulation of excess calories as triglycerides in adipose tissue is largely driven by insulin, and subsequent access to this stored fuel is gated by the β-adrenergic catecholamine receptors and their ability to stimulate lipolysis. The discovery of leptin as an adipose-derived hormone that can “report” on the status of these energy reserves to other organs of the body, including the central nervous system, gave us new perspective on adipose tissue biology (Barsh and Schwartz, 2002; Schwartz et al., 2003). In the ensuing years there has also been a deeper appreciation that a fairly large number of cytokines and growth factors are secreted from adipose tissue; they may play significant roles in insulin resistance, cell differentiation, and growth (Fig. 2) (Collins et al., 2004). These discoveries, and the appreciation that a host of biochemical and environmental factors contribute to the obesity epidemic, mark a new era in understanding how organ systems communicate their energy demands and reserves.

Figure 2.

Change in the complexity of the scientific view of adipose tissue over time.