How does the exercising muscle affect the metabolism of brown fat despite the anatomical separation of the two tissues?

There is very little that we, the crown jewel of evolution, have to be envious of lower mammals. Or so we keep telling ourselves. But there is one thing that always gave me a twinge of envy: Mice and rats have brown fat and we, except in infancy, don’t.

What is so great about brown fat? Unlike the white variety which is repository of calories, brown fat actually burns calories. Mice and rats don’t worry about overweight and diabetes. They use the brown fat for thermogenesis, or heat generation. When rodents are made to exercise, their muscles burn calories, just like ours. But the amount of calories burned by the muscles does not account for the total caloric loss; brown fat is responsible for the rest.

Furthermore, long after the exercise is over and muscle tissue returns to its resting state, caloric loss continues through the brown fat. Which begs the question: How does the exercising muscle affect the metabolism of brown fat despite the anatomical separation of the two tissues?


Beta Amino Isobutyric Acid (BAIA)

A paper in Cell Metabolism ( vol. 19, 96-108, 2014) titled “β-Aminoisobutyric Acid (BAIBA) Induces Browning of White Fat and Hepatic β-Oxidation and Is Inversely Correlated with Cardiometabolic Risk Factors” makes a great stride toward solving the mystery: A simple substance with the acronym BAIBA is the magic substance that converts white fat into brown, with all its attendant wonderful properties.

BAIBA, beta amino isobutyric acid
BAIBA, beta amino isobutyric acid

Robert Gerszten and his colleagues at Massachusetts General Hospital discovered the molecule BAIBA when they forced muscle cells to express the metabolic regulator PGC-1α. This regulator is very important in energy metabolism.

For example, it increases the metabolism of glucose in the mitochondria. It also has a long-term effect of increasing the number of mitochondria in the exercising muscle. As levels of PGC-1α increased with exercise, so did levels of BAIBA.

In animals treated with BAIBA, white fat tissue showed greater expression of genes linked to calorie burning, and the mice gained less weight and had better glucose metabolism than untreated mice.

What about humans? They found an inverse association between BAIBA levels and heart disease risk factors—people with more BAIBA in their blood also had decreased cholesterol levels and less insulin resistance.

As scientists are wont to say, more research is needed. The findings need to be independently verified. It is important to find exactly, on the molecular level, how BAIBA caused the changes in the fat tissue. Is it a direct effect on thermogenesis genes, or is it via other mediators? But one thing is already clear: BAIBA could be a target for drugs that treat diabetes and other metabolic disorders.


The Magic Bullet?

exercise benefits

Is BAIBA the magic bullet that will allow us to watch TV and lose weight doing it? Most likely not. We are a complex system comprised of many subsystems, which in turn are made up of thousands of sub-subsystems, all interconnected through multiple linkages.

All important functions are regulated by multiple systems, so that failure of one doesn’t doom us. When one component changes the overall equilibrium, other systems restore the status quo ante.

Taking a BAIBA-drug may allow you to stop exercising with impunity, for a while. Before long, the normal equilibrium reasserts itself. A prime example is the all too familiar of diet pills’ failure in the long run. Sorry, no short cuts exist, none are likely to be invented. Diet and exercise are still the answer.

Featured photo credit:

Dov Michaeli, MD, PhD
Dov Michaeli, MD, PhD loves to write about the brain and human behavior as well as translate complicated basic science concepts into entertainment for the rest of us. He was a professor at the University of California San Francisco before leaving to enter the world of biotech. He served as the Chief Medical Officer of biotech companies, including Aphton Corporation. He also founded and served as the CEO of Madah Medica, an early stage biotech company developing products to improve post-surgical pain control. He is now retired and enjoys working out, following the stock market, travelling the world, and, of course, writing for TDWI.



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