Can brown fat defeat obesity?
The subject I worked on when I went to my internship in Germany was brown fat cells, this subject has become very popular lately because these cells can help us treat obesity and diabetes. Many of us complain of excess fat in our body, these fats are white fat that accumulates when we gain weight, but we do not only have white cells in our body. Brown fats are typically known to produce energy and warm us up, especially in cold weather. These fats enable small animals such as mice to survive even in freezing temperatures. These fats, found in higher amounts in babies, are in small amounts in adults and almost entirely in a passive state. So why is science dedicating so much research funding to these adipose cells? Because our bodies can generate enormous amounts of energy using brown fat. It takes 3400 calories to burn 100 grams of brown fat completely. This is no small amount; because this amount is almost twice the daily calorie intake of many people, and we can fight obesity very quickly, and if we can understand the genetics and biochemistry of these fats, we can develop molecules that will activate them.
How Can We Increase Brown Fat?
When a person is exposed to cold, the body goes into an alarm state and states that it needs more heat. The nervous system then gives orders for the brown fat to both grow and burn. The other option is to simulate the nerve signal that makes brown fat grow artificially. Of course, if we are not extremely obese, it may not be right to do such applications. This may be considered a helpful option with lifestyle changes for morbidly obese patients. However, it should not be forgotten that every drug can have a side effect, so scientists do first animal experiments followed by 3-phase human trials. The real problem with increasing brown fat is that these fats require certain conditions to help us. Brown fats need a very high blood supply to be fully burned in the fight against obesity, and they also need to communicate with each other through nerves for brown fat to grow.
BMP8b Protein Can Turn White Fat Cells Brown
A protein called BMP8b was identified in mice by Samuel Virtue and Antonio Vidal-Puig, working at Cambridge University. This molecule was highly abundant in brown fat cells compared to white fats. This molecule was increased when the mice were exposed to the cold. This molecule is also present in humans and it has been determined that brown fat loses its function when deleted. Since this protein is found in the blood, it can be used as a drug to increase both its activity and amount.
Before human testing, the amount of BMP8b molecule was increased using genetic engineering in white fat and brought to the same level as the amount in brown fat cells. Later, it was observed that these white fats turned brown and their activity increased. BMP8b made the mouse more sensitive to signals from the nerves that activate brown fat. What was unexpected was that BMP8b also increased the number of blood vessels and the number of nerve fibers in white and brown fat.
To prevent and treat diseases such as obesity and diabetes, it is necessary to determine the mechanisms that protect our cells from metabolic stress. The elimination of protein wastes is one of these mechanisms. Professor at the Sabri Ülker Metabolic Research Center at Harvard University. Prof. Dr. Gökhan Hotamışlıgil and his team discovered that the director of this mechanism is the Nrf1 molecule. Prof. Dr. Hotamışlıgil said, “Our team has now discovered this compound. “We first saw that this process in the tissue was governed by a mechanism known as the “proteasome”, which is responsible for protein degradation, and then we revealed that the main regulator of the proteosome’s response to cold is the Nrf1 molecule.”
To determine the role of this mechanism in the disease, the research team used genetic engineering to delete the Nrf1 gene in brown adipose tissue. As a result, it was revealed that brown fat suffered from severe stress and inflammation, lost its properties, could not function properly, and therefore caused systemic metabolic disease. On the other hand, in obese individuals, when Nrf1 expression or proteasome activity (the general task of proteasomes is to remove damaged or useless proteins from the body via an enzyme) was increased, both body and tissue fat accumulation, metabolic disorders, and diabetes were dramatically improved.
References:
Widmaier SB, Snyder NA, Nguyen TB, Arduini A, Lee GY, Arruda AP, Saksi J, Bartelt A, Hotamisligil GS. NRF1 Is an ER Membrane Sensor that Is Central to Cholesterol Homeostasis. Cell. 2017 Nov 16;171(5):1094–1109.e15. DOI: 10.1016/j.cell.2017.10.003. PMID: 29149604.
