Nearly everyone took biology in high school, many in college and beyond. But most people—even those with science degrees—would probably fail a test today on the biochemistry of fat in the human body given all the latest science that has emerged over the past few years. It is breathtaking on one level and heartbreaking on another. In this chapter, I will tell that tale, starting with how a healthy, normally functioning body controls weight, and then move into the new science of obesogens and fat.
The diet community will have you believe that we know enough about the human body to design perfect weight loss programs that easily and permanently reduce anyone’s weight. Some (for instance, Weight Watchers) are based on the “calories in versus calories out” model—just reduce total caloric intake and you will be slimmer. The Atkins-style diet and its Paleo relatives allow as many calories as one wants, so long as very few of them are from carbohydrates (and most of these from vegetables). The Pritikin Diet and its derivatives (such as Ornish and South Beach) allow abundant complex carbohydrates but little to no fat.
Surprise: No one really knows exactly how all the inner machinery of the human body functions, particularly when it comes to weight gain and loss. This is especially true on an individual basis, as no two bodies are identical. If we knew exactly how everything worked, don’t you think that we could easily solve most problems in medicine today and prescribe a fail-safe weight loss program for you? Would there be any need for the colossal ($60 billion a year and growing) diet industry?
Assumptions about biology circulate like rumors. No one, for example, has challenged assumptions with respect to individual differences. How do some people gain weight under their skin (subcutaneous fat) while others pack on the pounds viscerally—around their intestines (which is very dangerous metabolically)? How these controls are set is not one-size-fits-all, which helps explain why there is no such thing as one diet (other than starvation) that works on everyone. Why do The Biggest Loser winners almost always gain back the weight they fought so hard to lose?57
In the previous chapter, I covered the main different body types you commonly see. There are people who seem to be naturally thin, those that are large, and individuals who are in between the two extremes (“average”). By the time you are an adult, your body has a natural tendency to maintain a certain weight and will adjust its internal processes accordingly. We call this the metabolic set point theory. This set point determines how much food you need to eat to gain weight, how much exercise you must do to lose weight, your propensity to food cravings and addiction, and how much you are willing to work for food. The set point programming for weight is not just genetically determined; it can be influenced by environmental forces and is largely set during critical periods of development, from in the womb through puberty. In the words of my friend and colleague Jerry Heindel, “A good start lasts a lifetime.” And a bad start sets an individual up for a lifelong higher risk of experiencing health challenges of all kinds—obesity among them.
An example of another set point is body temperature: if temperatures go above or below 98.6 degrees Fahrenheit (for instance, from exposure to a hot environment or an infection), a variety of physical mechanisms are activated in an attempt to bring the body temperature back to normal. Does this happen in the human body when it comes to weight? In other words, if your body goes above or below your set point range, does your metabolism rev up or slow down to get your weight back in your zone? The metabolic set point theory was originally developed by William Bennett and Joel Gurin to explain why repeated dieting is often unsuccessful in producing long-term change in body weight or shape.58 The theory was first described in the early 1980s, and since then numerous scientific studies have tried to find evidence for, and document, a set point that regulates human body weight.59 But as so many researchers have found, multiple variables factor into the weight equation; while there is some evidence to support the idea that an internal active control of body weight exists and has a sort of set point, it is not a fixed or immutable set point such as body temperature.
Not only does the body have more than one way to defend its fat stores, but body weight is the product of three main forces: (1) genetic effects (inherited DNA); (2) epigenetic effects (heritable traits that do not involve changes to DNA); and (3) the environment (diet, exercise, chemical exposure, sleep, and so forth). Regulation of body weight is complex and dynamic. It may even be asymmetrical—more effective in response to weight loss than to weight gain, which could help explain why it is easier to gain weight and keep the weight on than lose it permanently. We have learned a lot and have much more yet to discover, but at least we are beginning to understand the secret life of fat cells and how their behavior can change everything when it comes to weight.
Once you reach adulthood, the total number of cells in your body does not change much. Each type of cell has an average life span (for example, sperm cells have a life span of about three days; colon cells last only about four days; skin cells die and slough off after about two or three weeks; whereas brain cells typically last an entire lifetime). The average fat cell (known as an adipocyte) lives for about ten years.60 Although we know how the body creates new fat cells, we know little about how this number is determined. Early life programming tells the body how many adipocytes it is supposed to have, and the body will defend that number. If you remove some fat cells by liposuction, the body will restore the number of cells, but not necessarily in the same place as they were.61,62 Recent studies show that your diet can cause the number of fat cells to increase, but we do not yet know how to reduce the number of fat cells permanently. In order to significantly shrink the size of existing fat cells, you need to make substantial changes in what and how much you eat and maintain these changes. If you have increased your baseline number of fat cells through prolonged poor eating habits or from the impact of obesogens, you will struggle more with managing your weight because those fat cells are programmed to contain at least a minimum amount of fat. And as we will learn in chapter 3, small fat cells produce the least amount of the satiety hormone, leptin.
Later on, we will see how obesogens can affect one’s metabolic set point. But for now, let’s stick to the basics of normal fat metabolism and the road to obesity.
Contrary to popular belief, the road to obesity is not a straightaway. The human body is a lot more sophisticated and complex than most people realize or appreciate. As we further our understanding of fat metabolism and the development of obesity, we uncover fascinating new facts about fat. Fat cells are not all created equal. Moreover, different fat depots have disparate functional characteristics in terms of how easily they build and burn fat.
When I was in graduate school, the general thinking was that fat cells were mainly storage bins for excess calories. In other words, fat cells were seen as passive cellular containers for stored energy. They stockpiled energy and released it when needed. But it turns out that was a patently myopic perspective. Our understanding of fat tissue biology has progressed rapidly; fat has been recognized as a bona fide endocrine organ since the 1994 discovery of the satiety hormone, leptin,63 and the master regulator of fat cell development, peroxisome proliferator-activated receptor gamma (PPARγ).64 Fat tissue is an active endocrine organ that plays a key role in human physiology. Fat tissue releases more than twenty hormones, some of which are related to appetite and metabolism, that can communicate with other tissues, such as the brain, liver, pancreas, and immune system. Fat tissue, to be sure, is a key regulator of energy and nutritional balance in your body, and it is anything but passive.
The old adage in real estate circles is that the three most important factors in the value of a property are location, location, and location. This is also true for fat: where your body caches fat has health consequences, particularly with respect to heart and artery (cardiovascular) disease, type 2 diabetes, and stroke. As with cholesterol, there is “good fat” and “bad fat.” Fat stored inside your abdominal cavity (around your organs) is associated with most of the health risks of obesity and is considered to be “bad fat.” In contrast, fat stored under your skin (subcutaneous fat), like the kind of fat you see under your arms or as rolls on top of your abdominal muscles, is not associated with these health risks, although you might consider it the most unsightly.
To fully comprehend fat metabolism, it helps to first have a general understanding of how hormones work. Endocrine hormones are biological messengers produced in glands such as the pituitary, adrenal, ovaries, and testes that travel through the blood to other parts of the body, where they exert their effects. These biological messengers typically act at vanishingly small concentrations and have many important jobs in the body. Hormones act via highly specific hormone receptors. The presence or absence of hormone receptors determines whether a particular cell or tissue will respond to the hormonal signal or will instead ignore it. Broadly speaking, there are two types of hormone receptors. The first type are those that live on the cell surface and exert their function through a cascade of cellular messengers. These cellular messengers are called “second messengers” because they relay messages received at the cell surface from the first messenger—the hormone itself. For example, insulin signals through the insulin receptor, which acts through a group of second messengers that eventually elicit changes in gene expression. The second broad type of hormone receptor lives in the nucleus within the cell. It is what we call a nuclear hormone receptor, or nuclear receptor. These receptors are “ligand modulated transcription factors”; you can view them as molecular machines that bind to their specific hormone and directly regulate the expression of target genes. The estrogen and testosterone receptors are two examples of critical nuclear hormone receptors in the body.
There are more than fifty different hormones and related molecules that together regulate nearly every bodily process and are critical to the function of almost every tissue and organ. Hormones can regulate metabolism (how fast or slow it runs, whether you store or burn calories), growth and development between birth and maturity, tissue function, your moods, and much more. The diagram on the next page illustrates some of the key parts of the endocrine systems in the body and what hormones are produced by each.
At some point during your formal education you probably learned about the hypothalamus and pituitary glands in the brain, the sex glands (ovaries in women, testes in men), and the adrenals. Hormones are important for vertebrates and invertebrates and in many cases are very similar across species. The most well-known hormones are the ones we deal with daily, such as estrogen and progesterone, which regulate the monthly cycles of the female reproductive tract; testosterone, which gives men muscle and, in part, controls aggressive behavior; glucocorticoids such as cortisol, which regulate our response to stress; and thyroid hormone, which controls how many calories our bodies burn at rest. Insulin controls how much glucose is in our blood; insufficient insulin can lead to diabetes and a host of other health complications. Melatonin is required for our sleep/wake cycles. I could go on about many more hormones and their numerous important functions, but this introduction should be sufficient to illustrate the key role that hormones play in our lives and why disrupting their function can lead to many adverse health effects. Now let’s look more closely at the hormones controlling whether you get fat or stay lean.