Browning of Fat as a Tool in Obesity Resistance

From Wikipedia, PET/ CT scan showing brown fat in a human.
From Wikipedia, PET/ CT scan showing brown fat in a human.

Brown fat or brown adipose tissue (BAT) is metabolically active fat. It contains mitochondria, which contribute the brown color due to their iron content. Much has been learned about brown fat in the past 5-10 years, including that there is more than one type of this adipose tissue.

Not only is there brown, but also beige fat, or as the authors of this work (Schultz T.J., et al.) call it, recruitable brown adipose tissue (rBAT). The authors contrast the two brown fats by noting that constitutive brown adipose tissue (cBAT) is embryonic in origin and is found in the interscapular region of mice. rBAT is found in white adipose tissue (WAT) and in skeletal muscle in mice.

Furthermore,  these two  brown fats are from different cellular ancestors, cBAT coming from progenitors of skeletal muscle, while rBAT is derived from a non-myogenic lineage.

Bone morphogenetic proteins (BMPs) regulate the formation and thermoregulatory activity of BAT. In this report, the authors blocked a receptor for BMP, BMPR1A, by generating a mouse model that was missing BMPR1A in all cells carrying the myogenic marker Myf5+.

The researchers found that while the overall amount of cBAT in these knockout  mice was significantly lowered, and remained that way into mouse adulthood, the gene-expression pattern of residual cBAT in the mice was normal, although BMPR1A was abnormally low, due to the knockout effect. In these knockout mice, white adipose tissue (WAT) carrying the Myf5+ marker was also reduced, while Myf5- WAT populations were unaffected and carried a normal amount of BMP type 1 receptors.

However, a survey of skeletal muscle in the knockout mice showed that expression of BMPR1A was reduced by >95%. When skeletal muscle was normalized to body weight, they found that rather than a loss of limb skeletal muscle, myogenic progenitor cells were reduced. Thus loss of BMP signaling in Myf5+ cells specifically targeted cBAT formation.

Because BAT is key in thermoregulation, the Myf5-BMPR1a knockout mice should have reduced body temperature, due to their impairment of cBAT development. This was found to be true for newborns of this knockout type. However, the reduction in body temperature was no longer present in adult knockout mice, indicating that a compensatory mechanism had restored thermogenesis. The knockout mice did show a reduction in body temperature when exposed to cold temperatures such as 5°C after 2 hours and 48 hours. However, after exposure to cold for 11 days , the knockouts could regulate body temperature, suggesting  adaptive recruitment.

These mice, after prolonged cold exposure also showed a marked increase in UCP1 protein expression in WAT. (UCP or uncoupling protein is found in mitochondria.) The authors note that this browning effect could be enhanced in WAT of the knockout mice by administration of a beta-adrenergic receptor antagonist, which increased expression of certain BAT markers.

Because thermogenesis is controlled by the sympathetic nervous system, Schultz et al. quantified sympathetic input to WAT in Myf5- BMPR1A knockout mice. They noted increased staining of tyrosine hydroxylase in WAT of knockout mice (from Medpedia: the enzyme tyrosine hydroxylase  is important for normal functioning of the nervous system) and that circulating levels of noradrenaline were significantly elevated in these mice. The knockout mice, when exposed to cold, showed normal noradrenaline-induced thermogenic adjustment, and thus were able to compensate for the loss of cBAT.

Finally, the authors note that both genetic and surgical methods cited in this work “demonstrate the existence of a physiological mechanism to ensure thermoregulation by compensatory browning of WAT.” They  note that the system involved in rBAT formation seems to incorporate cBAT-brain and brain-WAT communication, mediated in part by the sympathetic nervous system.

What these and other researchers find most appealing about brown fat, is its potential link to obesity resistance. In mice, resistance to obesity seems to be tied mostly to browning of white fat, that is rBAT rather than cBAT,  suggesting that rBAT is “a key contributor to metabolic health”.

Editorial Note: I found the different ancestry of cBAT versus rBAT a very interesting duplication of systems. Makes one wonder: In terms of development, is rBAT the fall-back system for thermoregulation, in the event of cBAT failure?”

Here is a good review of brown fat from Searle and Lazar,  Diabetes (2009).


Schulz T.J., et al. (2013) Brown-fat paucity due to impaired BMP signalling induces compensatory browning of white fat. Nature, 495(7441),379-83.  Epub 2013 Mar 13.

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Kari Kenefick

Kari Kenefick

Kari has been a science writer/editor for Promega since 1996. Prior to that she enjoyed working in veterinary microbiology/immunology, and has an M.S. in Bacteriology, U of WI-Madison. Favorite topics include infectious disease, inflammation, aging, exercise, nutrition and personality traits. When not writing, she enjoys training her dogs in agility and obedience. About the practice of writing, as we say for cell-based assays, "add-mix-measure".

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