Feel the Chill: Brown Fat in Humans

‘Nothing burns like the cold,’ - George R. R. Martin, Game of Thrones.
Maintaining a healthy weight is a common problem for thousands of people, and generally people will go to great lengths to achieve this. What if I told you that you might lose some weight without dieting or even lifting a finger? Instead, all you have to do is subject yourself to a cold environment. No, this is not some sci-fi talk; researchers have recently discovered a type of fat in the human body that burns rather than stores energy and is activated by spending time in the cold. Now whether this can actually lead to noticeable weight loss is not yet clear. This type of fat is known as brown adipose tissue or BAT, or more commonly, brown fat.
In addition to white adipose tissue (WAT) that specializes in lipid storage, mammals are also equipped with thermogenic brown fat to dissipate large amounts of chemical energy as heat. In animals, researchers had found years ago that BAT most likely regulates body temperatures and is essential for survival in cold environments especially during hibernation. However, until about 10 years ago, BAT was considered to be only biologically active during cold exposure in human neonates to help them stay warm as they don’t have the ability to shiver. It is estimated that 5% of body weight of a human newborn/infant comes from brown fat, but BAT was considered to regress with aging by transforming into WAT. By combining 18F-fluorodeoxyglucose (FDG), an intravenously administered radioactive glucose analog that is also used in PET scans, and CT scans, scientists were finally able to image brown fat in adults in 20091.
But brown fat can be hard to find as it is located in unpredictable places in the body. Although it can be typically found in the region between the neck and shoulders (supraclavicular region), it is not always there in every single person. So identifying these metabolically active cells and studying them is a challenge in itself and scientists are working to find less invasive and expensive ways to do so.
Unlike rodents, where many studies have indicated that brown fat has profound effects on body weight, energy balance, and glucose metabolism2, the physiological significance of brown fat in humans is not well-understood. It is believed that generally in adults, brown fat may serve as an “internal heating jacket“ when exposed to cold environments. Several studies indicate that lower outdoor temperature, sex (female), lower age, lower BMI and plasma glucose levels, are all predictive of a higher prevalence of brown fat in individuals3.
So how does brown fat generate heat? Brown adipocytes in BAT are packed with iron-containing mitochondria, and in fact, brown fat gets its name from the dark red to tan color due to its high iron content. These mitochondria contain a unique protein called uncoupling protein-1 (UCP1). This is a transmembrane protein that decreases the proton gradient generated during oxidative phosphorylation by allowing protons to leak across the mitochondrial membrane. The proton gradient is normally used to drive the synthesis of ATP, so as a consequence of the leaking protons through the UCP1 action, the energy in the mitochondrial electrochemical gradient is released in the form of heat instead4. UCP1 is activated by the presence of fatty acids through the beta adrenergic receptor signaling cascade. From studies using the physiological stimulator norepinephrine, brown fat cells were found to chronically increase their metabolism 10-fold and produce heat at a rate of about 3 nanowatts/cell, corresponding to about 300 watts/kilogram of tissue5.
The burning question then is, does brown fat contribute to effective weight loss in humans? To address this, researcher Masayuki Saito of Tenshi College in Japan and his colleagues put cold to the test. In 2013, they had a small group of volunteers sit in a cold room at 19°C for two hours each day for six weeks6! It seems the study group participants lost a few percent of their body fat mass compared to the control group who showed no detectable change. It is estimated that as little as 50g of maximally stimulated brown fat could account for up to 20% of daily energy expenditure in an adult human7. Although by now it is an established fact that cold is a powerful stimulant for brown fat in animals, the main concern is how feasible this method of losing body fat for humans is as people are most likely not going to prefer spending two to three hours everyday in a cold room. Also, ironically, the fatter a person is, the less brown fat they have.
As you can imagine, this calorie burning brown fat has tremendous potential in the weight loss market. Several companies are racing to capitalize on this, but so far this has proved to be a tough nut to crack. There are reports about one company developing clothing that will cool the body! But the problem might be that it would be very uncomfortable to wear as most people don’t like to feel the chill. So, there have been several efforts to come up with alternative treatment plans. For instance, targeting UCP1 is a promising option, as are drugs targeting the beta 3-adrenergic receptor that can turn on brown fat and stimulate white fat simultaneously to release fat into the blood. However, it seems neither of these methods have resulted in any significant weight loss in humans so far. Finally, researchers have also tried brown fat transfer in animals, and a separate method in which they isolated fat precursor cells from one animal, differentiated them into brown fat in vitro, and reinfused them back into the animal. Both of these procedures have had some success in mice, but their applications to human patients is questionable. It seems studies in humans are still so new that there isn’t enough data to support any of these studies, but the hope in the scientific community of unleashing this fat burning power from within is quite strong. What are your thoughts about feeling the chill to shed those extra pounds? Let us know by emailing us at tech@biolegend.com.
References:
  1. Brown fat as a therapy for obesity and diabetes.
  2. Brown adipose tissue: function and physiological significance.
  3. Outdoor Temperature, Age, Sex, Body Mass Index, and Diabetic Status Determine the Prevalence, Mass, and Glucose-Uptake Activity of 18F-FDG-Detected BAT in Humans.
  4. The Biology of Mitochondrial Uncoupling Proteins.
  5. Thermogenic Responses in Brown Fat Cells Are Fully UCP1-dependent.
  6. Recruited brown adipose tissue as an antiobesity agent in humans.
  7. Identification and Importance of Brown Adipose Tissue in Adult Humans.
  8. Calorie-Burning Fat? Studies Say You Have It
Contributed by Mohar Chattopadhyay, PhD.
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