By now in our study of biochemistry, we are well aware of the fact that carbohydrates and lipids are sources of energy. We consume these energy sources as foods, convert the energy into ATP, and use the ATP to power our lives. Like all energy transformations, our energy consumption and expenditure are governed by the laws of thermodynamics. Recall that the First Law of Thermodynamics states that energy can neither be created nor destroyed. Translated into the practical terms of our diets,

This simple equation has severe physiological and health implications: according to the First Law of Thermodynamics, if we consume more energy than we expend, we will become overweight or obese. Obesity is generally defined as a body mass index (BMI) of more than 30 kg m⁻², whereas overweight is defined as a BMI of more than 25 kg m⁻² (Figure 27.1). Recall that excess fat is stored in adipocytes as triacylglycerols. The number of adipocytes becomes fixed in adults, and so obesity results in engorged adipocytes. Indeed, the cells may increase as much as 1000-fold in size.

We are all aware that many of us, especially in the developed world, are becoming obese or have already attained that state. In the United States, obesity has become an epidemic, with nearly 30% of adults classified as such. Obesity is identified as a risk factor in a host of pathological conditions including diabetes mellitus, hypertension, and cardiovascular disease (Table 27.1). The cause of obesity is quite simple in most cases: more food is consumed than is needed, and the excess calories are stored as fat. We will consider the biochemical basis of pathologies caused by obesity later in the chapter.

Before we undertake a biochemical analysis of the results of overconsumption, let us consider why the obesity epidemic is occurring in the first place. There are several possible, overlapping explanations. The first is a commonly held view that our bodies are programmed to rapidly store excess calories in times of plenty, an evolutionary adaptation from times past when humans were not assured of having ample food, as many of us are today. Consequently, we store calories as if a fast might begin tomorrow, but no such fast arrives. A second possible explanation is that we no longer face the risks of predation. Evidence indicates that predation was a common cause of death for our ancestors. An obese individual would more likely have been culled from a group of our ancestors than would a more nimble, lean individual. As the risk of predation declined, leanness became less beneficial.

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A third possibility, one currently receiving much attention, is that calorie-dense highly palatable foods—foods rich in sugar and fats—that are readily accessible to most people in the developed world, act as drugs, triggering the same reward pathways in the brain that are triggered by drugs such as cocaine. These reward pathways can be strong enough to override appetite-suppressing signals. Fourth, a growing body of research suggests that our intestinal microbiome—the bacteria that inhibit our guts—plays a significant role in how we process our food. For instance, germ-free mice do not become obese, even when given unfettered access to a high-fat diet. However, when such mice are exposed to the intestinal flora of obese mice, the mice now become obese even on a normal chow diet. Moreover, the intestinal microbiome of obese mice triggers an inflammatory response that may blunt the effect of signal molecules that normally regulate the desire to eat as well as how the mice process the calories they consume. Many of these results have been extended to humans. Finally, it is evident that individuals respond differently to obesity-inducing environmental conditions and that this difference has a large genetic component. Various studies have indicated the heritability of fat mass to be between 30% and 70%, indicating that the tendency toward obesity may be highly heritable.

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Regardless of why we may have a propensity to gain weight, this propensity can be counteracted behaviorally—by eating less and exercising more. It also appears that it is easier to prevent weight gain than it is to lose weight. Clearly, caloric homeostasis is a complicated biological phenomenon. Understanding this phenomenon will engage biomedical research scientists for some time to come.

As disturbing as the obesity epidemic is, an equally intriguing, almost amazing observation is that many people are able to maintain an approximately constant weight throughout adult life, despite consuming tons of food over a lifetime (Problems 1 and 2). Although will power, exercise, and a bathroom scale often play a role in this homeostasis, some biochemical signaling must be taking place to achieve this remarkable physiological feat.