Fat is not just fat. In other words, fat is not just a collection of energy storage cells. Fat is not just something that we resolve to lose come the new year. Fat, or adipose tissue, is dynamic and communicative and has the potential to control its own maintenance.
White fat cells. Flickr.
White fat
Fat comes in three flavors: white (abbreviated in the scientific literature as WAT, or white adipose tissue), brown (BAT) and beige. WAT is what we likely think of when we visualize fat. Its primary function is to store energy in the form of triglycerides (glycerol + three fatty acids). When the body needs energy from WAT, the triglycerides are broken down into free fatty acids. These freed fats are taken up by cells that further disassemble the fatty acids. Eventually, these fatty acid derivatives are fed into a cycle that produces ATP, the body’s basic energy molecule.
Hibernators, such as this arctic ground squirrel, use BAT to rewarm during hibernation. © Øivind Tøien.
Brown and beige fat
I’ve mentioned BAT in a previous LifeApps article. I’m interested in BAT because hibernating mammals use it to rewarm from cold core body temperatures. But all mammals are born with BAT (it’s one thing that sets us apart from other classes of animals) and small patches are retained in adult humans. BAT drives non-shivering thermogenesis, or internal heat production that is not generated by shivering muscles.Finally, beige fat can develop after prolonged exposure to cold. Beige fat is basically white fat that contains some brown fat-like cells. Intriguingly, beige fat may have the potential to counteract obesity by promoting lipolysis, or the breakdown of WAT for energy.
New research
Wenxin Song and colleagues recently published an exciting study in PLOS Biology. The most important finding is that the removal of organic cation transporter 3 (Oct3) in mice prevents uptake of norepinephrine into fat cells. More norepinephrine floating around outside fat cells, rather than inside of them, promotes “browning” of WAT and can increase lipolysis or fat breakdown. In other words, removing Oct3 from white fat cells can increase thermogenesis.
Breaking it down (the results and the fat)
Let’s step back. Oct3 is a protein that is found on white fat cells. As the name implies, it is a transporter. It brings extracellular catecholamines, hormones produced by the adrenal glands, into white fat cells. Norepinephrine is one such catecholamine, along with serotonin, epinephrine and dopamine. These molecules act as neurotransmitters in the central nervous system and as hormones in adipose tissue.
When norepinephrine is floating around outside of fat cells, it can activate β-adrenergic signaling, the first step in a long chain of reactions that can control the expression of thermogenic (heat-producing) genes. However, if Oct3 is around to take up excess norepinephrine, there is less WAT browning, less lipolysis and less thermogenesis. Removal of Oct3 (at least in mice and at least in this study) produces the opposite effect – browning of WAT, breakdown of fatty acids and increased thermogenesis.
[Note: the researchers also found that, in humans, some genetic variants of OCT3 (the gene that codes for the Oct3 protein) are associated with higher basal metabolic rate, or higher metabolism at rest. This means that humans may respond similarly to mice if Oct3 was removed to promote WAT browning and lipolysis].
Implications
Take-home message? Song et al. have discovered a protein (Oct3) that is key in mediating whether white fat stays white and stays put, or whether it turns beige and starts to break itself down. For those suffering from conditions associated with obesity such as diabetes, high blood pressure and heart disease, this is potentially very exciting news. Perhaps this discovery will lead to treatments that help people lose weight and find relief from life-compromising diseases.
From a scientific perspective, it’s another reminder that something seemingly as simple as fat (“just” an energy-storage tissue) can be intricate and complex.
