Fat cells feel cold?

Not all fat tissues are created equal. There’s the canonical white fat, which we associate with jiggle-ly belly aesthetics, long-term immflamation and Type 2 diabetes. Too much white fat accumulation in the internal organs has even been linked to lower cognitive function in young adults. While these fat cells provide insulation, they’ve always been regarded as inert. That is, they stubbornly hold onto their stored energy, even in chilly environments.

Then there’s brown fat –once thought to only exist in babies- that guards AGAINST obesity and diabetes. If you wipe out brown fatty tissue in animals through genetic deletion, the animals’ weights skyrocket. Brown fat is also more mobile: in response to cold, it releases its stored energy as heat. In other words, you burn off calories.

boneWAT

WAT vs BAT: White adipose tissue (white fat) vs Brown adipose tissue (brown fat). Do we have a winner here? Source: suppversity.blogspot.com

Sound like a clear-cut good fat/bad fat situation? Think again: new research suggests that “bad” white fatty tissue has a trick up its sleeve. Not only does it respond to cold, it can DIRECTLY sense cold temperature without relying on nerves.

Huh? How can fatty tissues sense temperature?

Let’s backtrack and talk about how brown fat works first. Imagine you’re jumping into the frozen arctic ocean (brrr). The terrible cold almost instantaneously activates sensory nerves in your body. These nerves signal to the temperature control centre – the hypothalamus at the base of the brain – that heat is desperately needed. In response, the hypothalamus releases norepinephrine, the major neurotransmitter in the fight-or-flight sympathetic nervous system. This mobilizes a protein called UCP1 that is present in brown fatty tissue, which triggers it to release its energy stores. Here, activation of the hypothalamus and sympathetic nervous system is absolutely necessary – mice bred without norepinephrine receptors are unable to mount this fat burning response.

Or so it seems. Scientists took these norepinephrine receptor(beta-receptors) lacking mice and exposed them to a chilly 10 Celsius (50 F) for 20hrs. In normal mice, this activated thermogenesis-related genes in two populations of fat: between-shoulder brown fat and subcutaneous (under the skin) fat. Unsurprisingly, in beta-receptor lacking mice, the brown fat response was almost completely obliterated, since they aren’t getting the trigger signal. However, subcutaneous fat more-or-less retained their ability to respond to cold, evidenced by robust thermogenic gene activation. Intriguingly, visceral fat (fat deep in the abdomen surrounding organs) did not respond to cold at all, in both normal and mutant mice. Since one major difference between these two populations of fat is that subcutaneous fat is closer to the surface of the body, scientists wondered if some types of cells in subcutaneous fat can “feel” and respond to cold autonomously, without the need for nerve activation.

So what are these cells? Scientists took lab grown white and brown fat cells and directly cooled them down. For good measure, they also included beige cells – white fat cells that behave somewhat like brown fat – in the study.

Screen Shot 2013-07-04 at 1.16.13 PM

Fig 3a from the paper. It helps to compare white vs beige vs brown. D16, J6 etc are just names of different cell lines.

As seen above, exposure to 31 Celsius (87.8 F) almost tripled the levels of UCP1 mRNA in white (3T3 and J6) and beige cells (D16 and X9), but didn’t change that in brown cells (9EB). Remember in fat-burning canon, UCP1 is the messenger that tells brown fat to start burning off its energy in response to signals from the nervous system. As you can see in the graph below, In white fat cells, the increase of UCP1 is reversible. That is, when heated back up to 37C, expression of UCP1 went back down to baseline. Furthermore, increasing ambient temperature did not induce the same change. This tells us that UCP1 didn’t upregulate due to a “oh my god I’m dying” general stress response, but that its increase is a specific response to decreased temperature.

Screen Shot 2013-07-04 at 1.15.29 PMChronic cooling of white fat cells increased the expression of a whole array of thermogenic genes, hinting that they have acquired increased ability to generate heat. Indeed, lowering ambient temperature significantly increased white fat cell metabolism, as measured by the rate of oxygen consumption.

Since lab grown cells can behave a little wonky at times, scientists also took “primary” cells in fatty tissue obtained from mice and humans and repeated the experiment. As before, both subcutaneous and visceral fat (having a mix of white and brown cells) responded to cold by increasing UCP1; pure brown fat, on the other hand, remained stoic. To confirm that this change is norepinephrine-independent, the scientists also analyzed markers involved in this signalling pathway, and showed that they were not activated.

So what do these results tell us? In all honesty, not that much. It’s really cool that white fat cells can directly sense cold and respond to it – this tells us that unlike popular belief, fatty tissue have a rich and interesting life that exceeds its function of energy storage. But where does UCP1 upregulation lead? It seems like increased UCP1 raises white fat cell metabolism, but does it generate enough heat for it to matter physiologically? Will cold exposure eventually decrease white fatty tissue mass, or will it be gradually repleted in the body? Can fat cells eventually be turned into calorie-burning weight-loss machines?

polar-bear

Polar bear swim, anyone? Anyone? Source: theprovince.com

Maybe their is some truth in promoting cold thermogenesis as a fat-loss measure after all.

ResearchBlogging.org
Ye L, Wu J, Cohen P, Kazak L, Khandekar MJ, Jedrychowski MP, Zeng X, Gygi SP, & Spiegelman BM (2013). Fat cells directly sense temperature to activate thermogenesis. Proceedings of the National Academy of Sciences of the United States of America PMID: 23818608

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One thought on “Fat cells feel cold?

  1. Exercise in a pill…again? – Neurorexia

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