Cold thermogenesis

Obesity is a modern pandemic, affecting, to varying degrees, all of the so-called industrialized nations.

In the U.S. alone, 75% of the population has problems with body weight. One worrying study reported that 25% of the calories consumed by American teenagers derive from snacks. It has been shown by several scientific studies that the life expectancy of a middle-aged obese person is decreased by eight years. Even in a person who is over 40 and overweight, there is a decrease of four years. The basis of obesity is the assessment of nutritional status and dietary behavior, and cognitive behavioral therapy for lifestyle modification. When change in diet is the only treatment, recurrence (regaining the weight lost) is very frequent, occurring in around 95% of cases. It is determined by biological factors (decreased energy expenditure), behavioral factors (restriction leads to loss of control), and psychological factors (loss of control and consequent transgression triggers depression).

Given the spread in several geographic areas, the high incidence rate, and the high mortality rate, the obesity epidemic is increasingly being discussed as an important issue. To explain the trend, the scientific medical community has proposed two distinct theories. The first, and most established, theory involves caloric imbalance. Consider the totality of calories consumed in food and beverages. If these are higher than the amount expended in the basal metabolic rate plus the energy spent through motor activity, there will be a positive caloric balance and consequent weight gain. Conversely, if the calories expended are greater than those consumed, there will be weight loss. It is a mere question of numbers.

The second theory involves a hormonal imbalance in the endocrine system. Hormones are chemical messengers that transmit messages from cell to cell (or between groups of cells). These substances are produced within the body with the purpose of modulating metabolic activity and the activity of tissues and organs. In most cases, when it comes to hormonal imbalance, this is a question of insulin. This hormone has anabolic properties and is produced in the pancreas; its main function is to reduce blood glucose levels through various metabolic processes. Insulin, with its anabolic activity, is responsible for energy storage, through the synthesis of lipids from carbohydrates.

In recent years, researchers’ attention has increasingly turned to the question of how energy is accumulated in adipose tissue, opening up new possibilities in the understanding of metabolic diseases and the treatment of obesity. There has been a relatively recent discovery of a type of adipose tissue with the function of producing heat. This tissue is primarily found in hibernating animals; until a few years ago, it was believed that it did not exist in humans, past infancy. Brown adipose tissue (B.A.T.) is named for its appearance. Its characteristic color is created by the presence of iron in the numerous mitochondria of this tissue type. Mitochondria are responsible for oxidative metabolism. The primary function is to produce energy necessary for cellular functioning; in addition, there may be the production of energy that is dispersed in the form of heat. It is precisely this aspect that differentiates the caloric model from the hormonal model; in the latter, a certain number of calories deriving from food can be dissipated through thermogenesis.

The body contains two types of fat tissue: white fat and brown fat. White adipose tissue is the most widespread in the human body, and functions to accumulate and store energy in the form of lipids. Brown adipose tissue has the function of burning energy and dissipating heat, with important thermogenic functions. Testing of laboratory animals on a diet known as the “cafeteria diet” (similar to the typical diet of Western countries, characterized by low-fiber, high-salt, high-fat, energy-dense foods and processed meat) has been shown in rats as well as in humans to cause considerable weight gain as well as to promote the development of diabetes. Taking rats that have a significant concentration of brown fat and putting them on the same diet, it is observed that the weight gain and the incidence of diabetes are less pronounced. The presence of brown fat in the latter group acts as a physiological protector, burning calories for heat and consequently lowering the levels of insulin, which are responsible for the onset of diabetes and the accumulation of fat. In this interpretation, we can define brown fat as a thermogenic organ. A portion of food that contains 300 kcal corresponds to about 50 grams of white adipose tissue; the same 300 kcal is the amount of energy consumed by 50 grams of brown fat for the production of heat over about 24 hours. In light of these results, given its ability to burn glucose producing heat and lowering insulinemia, brown fat represents an attractive target for the treatment of obesity.

It has always been known that babies are born with a certain percentage of brown fat. Because a newborn’s body volume is much smaller than that of an adult, a newborn has a greater surface area, and therefore a higher heat loss. Brown fat produces heat for the maintenance of body temperature. Additionally, adults have the capacity to produce heat through muscle contractions, or shivering. Babies do not have this capacity, so the entire production of heat is supported by brown fat. For many years, the protective effect of brown fat in the animals that possess it has been studied; however, its presence in adults has always been ignored, because it is located in different areas.

A few years ago, its existence was demonstrated thanks to the technology of the P.E.T. (positron emission tomography) scan, which is used for the detection of malignant tissue. A glucose-rich substance is injected, and this will be rapidly metabolized by the tissues that are most metabolically active. Among these tissues are the brain and the heart, as well as malignant tissues, which have a high metabolic rate and need to burn a large amount of sugar in order to proliferate. The areas where glucose uptake is highest appear dark on P.E.T. scan. As the cancer detection technique was developed, oncologists observed areas that had the same glucose uptake rate as the brain and heart, although they were not malignant. These areas are at the paracervical level, near the clavicles and scapulae, and around the kidneys – corresponding to the areas where brown fat accumulates in adults. In these regions, it is located near blood vessels, in order to spread the heat that it generates through the blood flow. Its primary function is to oppose the loss of body heat in low temperatures. This reaction is known as cold thermogenesis, or thermoregulation at low temperatures.

Brown adipose tissue is present in varying amounts in all adults. Its absolute weight varies from 30 to 250 grams per individual. If one considers its potential metabolic activity, it could burn up to 3 to 5 kg of fat in a year if constantly stimulated. To find out whether those with more brown fat are thinner, a study was carried out on 2934 adults. It was shown that women, thinner people, and those with a lower glycemic index all had more brown fat. In other words, it was demonstrated that the relative amount of brown fat was correlated with thinness and with lower glycemic index.

In laboratory experiments, it has been demonstrated that brown fat is not metabolically active at a constant temperature of 25ºC. P.E.T. scan shows that lowering the temperature by just 6ºC (to 19ºC) leads to a net activation of the adipocytes of brown adipose tissue. This activation coincides with the production of heat. Our body is able to record and interpret environmental conditions through two distinct systems. One is the nervous system, which receives signals through neurotransmitter receptors. The other is the endocrine system, the role of signal messenger is played by hormones. One of the most striking discoveries regarding brown adipose tissue is that it is able, when subjected to low temperatures, to produce hormones. These hormones enter the bloodstream and have the ability to transform white adipose tissue into brown adipose tissue. This extremely important process of converting energy reserves into a thermogenic organ is known as the thermogenic browning effect. When laboratory rats are treated with brown fat hormones, the conversion and activation of brown adipose tissue occurs, with subsequent calorie consumption and production and dispersion of heat.

Brown fat is defined as such due to the very high number of mitochondria present, which give it its characteristic brown color. Mitochondria are organelles that are considered the cell’s energy center. Within them, cellular respiration takes place, which results in the production of a large amount of energy in the form of adenosine triphosphate (ATP). The generation of heat in brown fat cells occurs with an interruption of the respiratory chain, allowing a fast oxidation of the substrate with low ATP production. This operation of uncoupling the respiratory chain is mediated through a protein called thermogenin, also known as uncoupling protein (UCP). This protein occurs only in brown adipose tissue, where it provides the mechanism for enormous heat generation. This non-chilling thermogenesis is the main source of heat production in hibernating mammals and newborns.

Post by Ivo Pirisi

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