Brown fat: The hopeful path to curing obesity and diabetes

By Chandreyi Banerjee


Fat. The word conjures up a multitude of negative connotations, from an unpleasant epithet to the host to numerous diseases and conditions like diabetes and obesity. Who would have thought the power of fat in our bodies could be harnessed to fight off the very illnesses that we associate fat with? This so-called magical fat is one of the three main kinds of adipose tissue (a specialized connective tissue consisting of lipid-rich cells called adipocytes) in our body; it is brown fat.


The function of brown fat in the human body

In human bodies, there are two primary types of adipose tissues: white fat and brown fat. White fat stores energy in triglycerides, whereas brown fat produces heat when activated by cold temperatures in a process called thermogenesis. This is made possible by many more mitochondria in brown fat than white fat. With mitochondria, the brown colour of the fat is likewise explainable due to the presence of iron in mitochondria. In addition, the brown fat-specific uncoupling protein (UCP-1), residing in the internal mitochondrial membrane, dissipates the proton-motive forces of the intermembrane space of the mitochondria and produces heat rather than the normal ATP, as shown in this diagram. Thus, the primary function of brown fat in the body is to generate heat.



Source- (Adipose Tissue, n.d.)


Evolution of brown fat

Brown fat was discovered about 500 years ago in a hibernating species of mammals known as marmots; however, it was then incorrectly deemed to be a gland found only in hibernating animals, whose main purpose was to generate heat to pull the hibernating animals out of torpor(a state of slowed body functions used to conserve energy and heat). It was in the last 100 years that scientists have realized that this "gland" is indeed a special type of fat, found in the highly vascularized(present in vessels) deposits: between the shoulder blades, surrounding the kidneys, the neck, and supraclavicular area, and along the spinal cord.


Recent technological development of the PET(Positron emission tomography), a type of medical imaging, has allowed Large-scale studies of brown fat to be carried out in the population. For example, a recent study of over 50,000 people undergoing PET scans for various conditions found that several common and chronic diseases were less prevalent among people with detectable brown fat. For example, only 4.6 per cent had type 2 diabetes, compared with 9.5 per cent of people who did not have detectable brown fat. The challenge for scientists now is to find ways to activate thermogenesis to harness the power of brown fat to treat various health conditions. Below are just some of the ways this has been made possible by the scientific community.


Methods of activation of brown fat:


Enhancing Melatonin production

Melatonin is a hormone generated in the pineal gland in our brain in reaction to variations in light. It is produced in response to darkness, which results in more significant amounts at night.


Scientists have discovered that melatonin can be used to control body weight issues. In a study, even if they ate the same quantity of food, rodents receiving daily melatonin supplements acquired less weight than those not receiving one. For six weeks, half of each strain was regularly fed. The remaining half had the same meal plus melatonin. The researchers next looked at the fat below the skin near the shoulder blades of the animals. Over the six weeks, obese melatonin administered rats acquired more beige fat.


Inhibiting Serotonin

Serotonin is an important hormone that stabilizes our mood, feelings of well-being, and happiness. It has been found that Serotonin exists at higher levels in the bodies of people with diabetes or who are obese. Researchers have found that inhibiting the body's production of serotonin in mice switches on their brown fat, protecting them from developing obesity, fatty liver disease, and diabetes.


Gene therapy

In this process, researchers took developmental-stage human white fat cells. They used a gene-editing technique using CRISPR technology to boost the expression of a gene called UCP1, which triggered the white fat cells to develop into brown-fat-like cells. As a result, mice injected with white fat cells acquired more weight, but those with brown fat acquired much less; they were also more responsive to insulin, thus explaining why brown fat might protect against diabetes.


Stem cell therapy

Another researched technique of brown fat activation is isolating white fat cells from patients surgically, treating it with substances to encourage specialization of the white cells into brown adipocytes and then replanting them in the human body. One method of replanting the brown adipocytes is the use of 3D alginate hydrogel micro stands. The brown fat is encapsulated via this biomaterial that protects the cells from rejection by the person’s immune system.


Exercise?

A protein hormone called irisin is secreted by skeletal muscles undergoing a period of intense exercise. Irisin has been shown to increase the rate of cellular respiration by increasing the UCP-1 proteins in the mitochondria, transforming white fat cells into something called beige cells that have properties of both white fat cells and brown fat cells.


Conclusion

Brown fat activation is an exciting field for research that has shown much potential to cure obesity-related diseases. However, much of the research highlighted have not reached its clinical phase to be implemented as a therapeutic tool. Like any other scientific breakthrough, this requires the joint effort of hundreds of scientists working in this field. Soon we will have obesity-related diseases cured as well, like the hundreds of common diseases now lost in the annals of history.


References:


Hamzelou, J. (2020). Body fat transformed by CRISPR gene editing helps mice keep weight off Read more: https://www.newscientist.com/article/2252925-body-fat-transformed-by-crispr-gene-editing-helps-mice-keep-weight-off. https://www.newscientist.com/article/2252925-body-fat-transformed-by-crispr-gene-editing-helps-mice-keep-weight-off/#ixzz70H3mDixh


ROCKEFELLER UNIVERSITY. (2021, Jan 4th). Study of 50,000 people finds brown fat may protect against numerous chronic diseases. Retrieved June 3rd, 2021, from https://www.eurekalert.org/pub_releases/2021-01/ru-so5010421.php


Marcin, A. (2020). Brown Fat: What You Should Know. https://www.healthline.com/health/brown-fat


Cyprus, A. M., & Kahn, C. R. (n.d.). Brown fat as a therapy for obesity and diabetes. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3593105


Adipose tissue. (n.d.).

https://www.biology-pages.info/A/AdiposeTissue.html