Turning White Fat to Beige Fat - New Disconfirming Evidence on IL-4 Contribution [Research]

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Unlike white fat, brown fat, also known as brown adipose tissue (BAT), can play a heavy role in the energy-out side of the energy equation (increase the amount of calories burned).

The major physiologic role of BAT is to release energy as heat instead of harnessing it for other purposes - which most of the rest of the cells in the human body do. So, BAT uses uncoupling protein 1 (UCP1) to dissipate the energy in the electrochemical gradient in the mitochondria instead of using it for ATP synthesis.

Why and when does it do this?

• to heat the body in different situations, one of them being exposure to cold, therefore the terms: cold-adaptive/cold-induced thermogenesis.

Thus, brown adipose tissue is more like a heat generating source, unlike white fat (that most of us carry on our belly):

"Two discoveries have elevated interest in thermogenic adipose tissue. One is the realization that there is an inducible form of thermogenic adipose tissue, termed beige or brite adipose tissue, with a transcriptional profile and developmental origin distinct from BAT (Wu et al., 2012). Another is that humans have measurable brown or beige adipose tissue, which can be activated by drugs or cold (Cypess et al., 2015)." [source]

In the research community there is a large interest for beige fat or brown adipose tissue as tools to help in the treatment of obesity:

"The classic view of BAT physiology is that sensation of cold is transmitted to the brain, through which it eventually causes sympathetic neurons to release norepinephrine, stimulating b-adrenergic receptors on the brown adipocytes (Morrison et al., 2014). The BAT activation process also includes glucose and lipid mobilization, with greatly increased blood flow to the BAT in order to both supply these fuels and remove and distribute the heat that is generated (Cannon and Nedergaard, 2004)." [source]

Now, the nitty-gritty:

Until recently, it was proposed that Interleukin-4 (IL4) activation of macrophages plays a crucial role in cold thermogenesis, as it stimulates macrophage catecholamine production for the recruitment of beige fat. There were even studies that showed that treating mice with IL4 lead to increased 'beiging' and increased energy expenditure. According to Reitman (2017):

"Now a collaboration of six laboratories in four continents has carefully examined this pathway, including the role of IL-4, macrophages, and macrophage-derived catecholamines (Fischer et al., 2017)." [source]

In short, through a series of experiments, Fischer and colleagues (2017) reported that IL4 does not lead to higher adipose thermogenesis and that activated macrophages do not lead to catecholamine production.

There are many ways to stimulate brown-adipose activation or the beiging process and they may involve both endogenous and exogenous mechanisms:

"Could one or more of these pathways be induced by cold exposure, possibly interact with type 2 cytokine signals, and increase norepinephrine release from sympathetic neurons or other cells? Despite the relative sparsity of sympathetic innervation to WAT, methods exist to study the neural input (Zeng et al., 2015) and the role of the sympathetic nervous system in beiging, which needs to be re-evaluated." [source]

Thus, to further elucidate BAT physiology and the mechanisms of cold-induced thermogenesis, we need all types of research, even disconfirming ones like this one (this type of research is less sought after, though).

As a side note, I like reading elegantly-put disconfirming/refuting research reports :)

And this post was not intended to reveal some sort of extraordinary discovery or the latest science-news fad. It was taken from the mundane annals of daily published research papers looking into the very specific details of a sub-field of research.

For the geek, if you are interested in the technical details of the experiments conducted by Fischer and colleagues (2017), you can read their paper here:

[Alternatively activated macrophages do not synthesize catecholamines or contribute to adipose tissue adaptive thermogenesis]

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Cristi Vlad, Self-Experimenter and Author