Beige is the New Brown (Fat)

Mind the Gap: Beige is the New Brown (Fat)Since defending my thesis I’ve been repeatedly putting off starting the diet and exercise regime needed to lose the excess pounds I gained while writing it. Sadly, the time has come for my procrastination to end and the torture to begin, and on September 1 I will put the Insanity DVD into my computer, actually work out, and stop eating delicious things like bread and pasta and French fries. Tear.

But what if I could just convince some of my copious amounts of white adipose tissue to become brown?

Animals have three types of fat (a.k.a. adipose tissue) composed of different types of adipocytes (fat cells). White adipose tissue is the most common, and it’s the stuff that builds up when you gain weight. It is also metabolically relatively inactive and acts as an energy store. Brown adipose tissue, on the other hand, is extremely metabolically active and is involved in maintaining body temperature through using the chemical energy found in food to generate heat. Humans only have very small amounts of brown fat, with deposits found at the back of the neck and along the spinal cord.

The third type of fat cell is the beige adipocyte. These cells are found in white adipose tissue, and appear to be the result of white fat cells taking on certain characteristics of their brown counterparts, in particular their energy burning ability, rather than representing a distinct cell type. This is particularly exciting for those of use with a bit too much white adipose tissue: What if we could coax white cells to become beige? Could we brown our white fat (“of course, not in a skillet, but directly inside the body”, joked lead author Prof. Dr. Alexander Pfeifer), burn more energy, and eat cake while loosing weight?

The conclusion of a study by German scientists published this week in Science Signaling is perhaps. Using mice, the authors found that a particular signaling pathway is involved in regulating the energy-burning potential of fat cells. The activity of a protein called vasodilator-stimulated phosphoprotein (VASP) is critical in the differentiation of fat cells, and mice lacking this protein showed increased browning of their white fat and a reduced body mass compared to their wild type litter mates. Without VASP, the knockout mice showed increased levels of cyclic GMP, a small molecule that is involved in transmitting cellular messages between proteins. Importantly, high levels of cyclic GMP are required for brown fat cell differentiation through the activity of protein kinase G. Thus, by knocking out VASP the authors were able to increase beige adipose tissue levels and rear lean mice. In normal mice, VASP acts as a negative regulator of cyclic GMP levels. The authors found that in the white adipose tissue of these animals a negative feedback loop was initiated when cyclic GMP reached a certain level through the activation of VASP.

While this pathway has, for now, only been demonstrated to work in mice, it represents a potential therapeutic target for the treatment of obesity. Cyclic GMP is a molecule involved in a number of cellular processes, so indiscriminately up-regulating its production would be dangerous. However, interfering with the VASP feedback loop in white adipocytes represents an exciting area for further research.

So it would seem that, at least for now, I’m going to have to shift the thesis weight the old fashioned way. Sigh…

 

Katie PrattKatie Pratt is a postdoc in Molecular Biology at Brown University. She has a passion for science communication, and in an attempt to bring hardcore biology and medicine to everyone, she blogs jargon-free at www.katiephd.com. Follow her escapades in the lab and online on Twitter.

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3 comments so far. Join The Discussion

  1. Subhasree Nag

    wrote on August 29, 2012 at 2:49 pm

    Protein Kinase G

  2. alan@benchfly

    wrote on August 29, 2012 at 3:02 pm

    We've got a winner!

  3. Olivier Boss

    wrote on August 29, 2012 at 10:15 pm

    There is really nothing new. "Beige" is a new name for a well known, already described induction of brown adipocytes (expressing UCP1) in white adipose depots. They are called "brite" (for "brown-in-white") adipocytes. These cells have been shown to arise by two types of mechanisms: transdifferentiation of white adipocytes into brown adipocytes (induction of brown features, markers) and differentiation of novel brown adipocytes from progenitors.
    Until now, all stimuli (e.g. cold temperatures, beta-AR agonists, cAMP analogs, adenylate cyclase activators, PPARg activators/TZDs, and even cGMP analogs, PKG activators) that activate or increase the recruitment of brown adipocytes do so on all "kinds of brown adipocytes" (brown, brite/"beige").
    Indeed, this makes physiological sense as the purpose of inducing "brown fat" (any kind) is to produce heat/dissipate energy: to keep body temperature warm and to prevent weight gain.

    [BTW, I don't mean to disparage the work by Andreas Pfeifer (it's great) or anyone else's, I just want to clarify that the newly used (by some) term "beige" is in fact an already described type of brown adipocytes called "brite" for years now (I believe Jan Nedergaard and Barbara Cannon proposed this term first).]

    Olivier Boss, PhD – Energesis Pharmaceuticals (Cambridge, MA, USA)

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