Neurobiologists at Yale University School of Medicine recently found that the thyroid hormone triiodothyronine increased in fasting mice, activating an "uncoupling" protein that disrupts the breakdown of food into energy. In turn, the number of mitochondria, the cellular factories that convert food into energy, increased in neurons responsible for stimulating appetite. When the ravenous mice were fed, they ate more food than they needed.
On the other hand, says Sabrina Diano, lead author of the study published in this months issue of Cell Metabolism, there was no increase in mitochondria in fasting mice that lacked the uncoupling protein, and they ate less than their littermates when food was reintroduced to them. Diano says the findings suggest that the uncoupling protein's effect on mitochondria in brain cells plays a critical role in regulating the neurons that direct energy metabolism. The dysfunctional mitochondria in the brain may also be important players in obesity and diabetes, conditions that are influenced by the ability of mitochondria to metabolize food into energy in muscle, liver and other tissue in the body.
Researchers believed that when the level of leptin, a hormone produced by fat, drops during fasting, the brain receives a chemical signal that triggers neurons to produce energy. Prior to this study, little was known about the function of fasting-induced uncoupling protein. But the Yale researchers found that when mice fasted for 24 hours, the hypothalamus region of the brain, which controls body temperature and hunger, showed an increase in uncoupling protein activity as well as in the type 2 deiodinase enzyme that helps manufacture the thyroids active triiodothyronine hormone in the brain.
Thyroid hormones regulate metabolism, but are also involved in controlling body temperature. Triiodothyronine is involved in fasting and also activates a related uncoupling protein that helps regulate the body's temperature. When activated, the protein indirectly decreases the efficiency of energy production and generates heat as a result. Similarly, the number of mitochondria in the neurons also increased and became active during fasting, according to the study. "We found a cellular mechanism in the brain that is similar to one in the periphery tissue involved in body heat regulation," Diano says.
Next, the researchers hope to determine if the increased activity in neurons is specifically related to the thyroid hormone or if other hormones are involved. Diano also plans to look into whether the mechanism that is activated during fasting has thermogenic consequences in the brain and "whether heat may serve as neurotransmitters in activating neurons in the brain." If so, she says temperature variations could have "big consequences for the brain."