Managing weight in the body is like orchestrating a complicated symphony that takes on a life of its own. The conductor could be likened to the hypothalamus, the brain’s thermostat for temperature, energy expenditure and energy storage. It signals which instruments to play at certain times and amplitudes. These instruments are the glands and hormones of the body that carry out the conductor’s will. When weight management is optimal, the hypothalamus and all its players move in sync, each fulfilling their relationship to one another, each contributing to the greater functional whole. But sometimes, the glands and hormones, the hypothalamus, or fat cells can be dysfunctional. They may play too loudly, too many notes, or simply not work in relation to the other players. When this occurs, the symphony is like a runaway train. The hypothalamus will try to keep up or slow the players down, but ultimately, new norms will establish, and the conductor loses control of what the greater functional whole was. In this article, I will go into more detail about the key players in the physiology of weight gain so that we can gain an understanding of what we have going against us when we try to lose weight.

The first thing to understand is that fat is composed of fat cells called adipocytes. These cells have the function of storing fatty acids in periods of low energy expenditure and to be able to mobilize fatty acids when the body needs energy. Through decades of research, we now know that they are more dynamic and more complicated than that simple function. Adipocytes produce many products that have a wide-ranging effect in the body. They also actively respond to a variety of hormones.

Secondly, excess fat can be composed of either adipocytes that are too big (hypertrophic) or too many adipocytes (hypercellular). Hypertrophic obesity typically occurs in adulthood. It is associated with an increased risk of cardiovascular events, but it usually responds well to weight loss efforts, which also decreases cardiovascular risk. Hypercellular obesity is more difficult to address. It usually begins in childhood or in morbidly obese individuals.

So what are these adipocytes doing in the body? What are the signals that help them perform optimally? Like every cell in the body, adipocytes undergo a process of becoming a mature cell and are under surveillance to assure proper function. If they are misbehaving, a healthy immune system will eliminate a dysfunctional fat cell. Pre-fat cells become mature fat cells by various transcription factors, or biochemicals that influence genes. They have the ability to influence the development of healthy fat cells and to signal the demise of dysfunctional fat cells. We’re starting to realize that they are particularly important in the role of keeping weight off after weight loss. By keeping these transcription factors active, we are essentially restructuring the fat cell makeup of the body. At the same time, dysfunctional and hypertrophic fat cells have some influence on the immune system by secreting biochemicals to ensure their survival. Some of the molecules they produce will inhibit immune complexes from detecting and destroying them. These adipocytes are especially prevalent around visceral organs.

Besides the internal biochemicals to which fat cells respond, healthy adipocytes secrete influencing molecules as well. Of the many chemicals adipocytes secrete, most fall within the following categories. Some increase inflammation, some are involved in the clotting cascade, some regulate appetite, and others moderate insulin sensitivity. If you came to my Diet and Inflammation lecture, you will know that pro-inflammatory chemicals can contribute to various diseases. Interestingly, inflammation is a consequence of obesity, not a cause of obesity. The signals involved in the clotting cascade increases the risk of cardiovascular events such as stroke, thrombotic emboli, and heart attack. Adipocytes produce leptin, which is a hormone that communicates to the hypothalamus that you are no longer hungry. If a person has more adipocytes or larger adipocytes, you would think they would have plenty of leptin to depress the appetite. Though it’s true they do have higher levels of leptin in the blood, receptors to leptin no longer respond to high concentrations. Tissues with leptin receptors in the brain and elsewhere develop a leptin “resistance” similar to insulin resistance in people with Type II diabetes. Eating a diet high in fructose (found in processed foods with high fructose corn syrup and a diet comprised of only fruits) decreases circulating levels of leptin in rats. Lastly, healthy adipocytes secrete adiponectin, a blood protein that has many functions in the body. It is found to be decreased in people with Type II diabetes. It affects increased uptake of glucose, increased mobilization and breakdown of fatty acids, protection of blood vessels, and increased insulin sensitivity. So it’s easy to make the connection between having a composition of dysfunctional fat cells  and being susceptible to diabetes.

There are many hormones at play in the physiology of weight gain. We’ve already talked about leptin and its ability to suppress appetite to signal to the body that there are enough fat stores and to decrease caloric intake. Its counterbalance is ghrelin. Ghrelin is a hormone produced by the stomach lining that signals to the hypothalamus that we are hungry and to start activating digestion. These function of these two hormones can give some insight to how sleep plays an important role in weight gain. Short sleep duration is associated with increased production of ghrelin and reduced production of leptin. This makes perfect anecdotal sense. If you’ve ever had to pull a late night or an all-nighter, you probably have experienced being extremely hungry especially for carbohydrates in the days following. Eating patterns can also have an effect on sleep. One study showed that night time eating lessened the production of melatonin (the hormone produced at night to induce sleep), increased cortisol production (a hormone that has vast effects on maintaining energy to handle daily stress), and increased morning levels of leptin. Increased morning levels of leptin depresses the appetite and makes one not want to eat breakfast. This pattern may be prevalent in obese individuals who also experience insomnia. This is a particularly damaging cycle to be in because it shifts the appetite to an irregular eating pattern in relation to sleep, in a way that disrupts sleep. And less sleep will disrupt hormonal patterns that effect both appetite and metabolism.

Cortisol has a complicated role in weight gain. The many roles it plays is still uncertain. As mentioned above, cortisol is secreted in periods of stress. It is also secreted daily to function as a hormone that helps us stay alert and function throughout the day. It has wide effects on the immune system. It will suppress inflammation, which is a tool the immune system uses to combat disease. Therefore, it is very useful in conditions with unchecked inflammation, yet at the same time will depress the immune system and can cause increased likelihood of infections and poor healing. Cortisol also influences glucose uptake after eating. It increases stomach acid and appetite. With chronic daily stress, too much cortisol can lead to peptic ulcers, or overeating. But it also has an effect on the hypothalamus and neuroendocrine system in the digestive tract that is not yet clear. On the other side of emotionally charged biochemicals, endocannabinoids, those that are external and those that are internally produced, will stimulate appetite and increase the absorption of nutrients. It has a strong affect in the hippocampus, the site of memory and the limbic system (emotional component of the nervous system that contributes to feelings of anger, joy, sadness, fear, worry, and grief). Though it is unclear, this connection may help to explain why there is such an emotional component to overeating.

Weight gain in Menopause is a common phenomenon. Research shows there are metabolic and appetite regulation functions of estrogen besides its nonreproductive effects on the brain, cardiovascular system, and bones. (Estrogen is like the embodiment of “the woman of the house”–multitasking and keeping all systems in check!) Studies show that deprivation of estrogen signals the brain to be in a hunger state and can cause overeating. It also signals to the hypothalamus to depress metabolic activity. Deprivation of estrogen doesn’t only mean not producing as much. Instead, it may be a consequence of an overabundance of proteins that convert estrogen to other compounds or it may mean that there is impaired response at the target tissue (impaired estrogen receptors). Remember, it always takes at least two to communicate. In this case, you have something producing the message, estrogen is the message, and something to receive the message. Furthermore, once the ovaries retire during menopause, they sort of pass the torch in regards to estrogen production. Fat cells are the major producers of estrogen after the ovaries quit. It is worthwhile to consider if a proliferation or growth of fat cells plays a role to maintain homeostasis around menopause. So far, it is not recommended to use hormone replacement therapy as a way to treat weight gain due to its increased risk of clotting and emboli and developing endometrial, ovarian, and breast cancers. Rather, there are ways to optimize peri- and post-menopausal hormonal states through diet and physical activity.

I’ve focused primarily on the physiology and function of fat cells. By doing so, I’ve neglected to explain how exercise effects adipocytes. After blood glucose levels are depleted for energy, the liver and muscles will make more glucose for muscle energy expenditure. There is a slow way and a fast way to produce glucose. During strength training and focus on anaerobic exercise, the body will utilize the fast track, which is responsible for the lactic acid feeling or sore muscles after working out. During aerobic exercise like long distance running and swimming, the body mostly utilizes the slow track of glucose production. The body is constantly breaking down fatty acids (stored in adipocytes) during these activities. The best way to encourage fatty acid breakdown is by exercising regularly with a combination of resistance activities and aerobic activities.

When losing weight, adipocytes either shrink or shrink in numbers. This will result in less leptin production. Remember leptin tells the body that you’re full. So there will be a period of three to twelve months when one will have increased desire to eat because their signals of being full are less. It will also contribute to decreases in thyroid hormone causing lowered metabolism and decreased muscle tone for a period of time. The decrease in leptin is lower than in a person of the same size that was not losing weight. This is because the conductor thermostat, the hypothalamus is still at the slower tempo and it is trying to maintain what was normal before. So during weight loss, it is important to take extra patience (one  to two years!) to establish a new normal–a symphony with a faster tempo.

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