A recently discovered regulatory mechanism helps the body control the rate of fat metabolism, according to a new study published January 17 in the open access journal. Biology of the PLOS by Ligong Chen from Tsinghua University in Beijing and colleagues. The finding may lead to new medications to help burn stored fat and reduce weight.
The fatty tissue can be white, brown or beige, differing not only in color but also in metabolism. White fat is primarily a storage tissue, with a low rate of metabolism; Brown fatty tissue, on the other hand, is rich in mitochondria and burns stored fat, releasing heat to warm the body, a process called thermogenesis. After a prolonged exposure to cold, the brown fat cells develop inside the white fat, making it beige, and the beige fat cells also burn the fat to keep the body warm.
A key stimulus for thermogenesis is the hormone norepinephrine, which exerts its effects on the cell surface, and is then absorbed by the cell and degraded to prevent overstimulation. A mechanism for norepinephrine uptake of fat cells has been described above, but its uptake rate is relatively low, suggesting that there may be another pathway.
In the new study, the authors found that beige fat cells in mice have high levels of a protein called an organic cation transporter 3 (Oct3), which can import norepinephrine into cells for degradation. The authors showed that reducing the level of Oct3 and, therefore, reducing the degradation of norepinephrine, led to a higher rate of fat metabolism in beige fat and a higher body temperature. When exposed to prolonged cold, mice deficient in Oct3 increased the beige fat content faster than their litter controls, accompanied by increased activity of the biogenic thermogenic and mitochondrial genes.
Remarkably, when they looked at the human genetic badociation databases, the authors found that having versions of the OCT3 gene that produce the OCT3 protein with a reduced transport function was badociated with a higher metabolic rate. Taken together, these results indicate that OCT3 plays an important role in regulating the rate of beige fat production and thermogenesis in mice and humans.
"Our discovery that a reduction in OCT3 activity can lead to more beige fat and an increase in thermogenesis, indicating the importance of this transporter in the recycling of catecholamine in adipose tissues," Chen said. "The development of specific inhibitors of OCT3 would open new therapeutic possibilities for metabolic diseases."
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Song W, Luo Q, Zhang Y, Zhou L, Liu Y, Ma Z, et al. (2019) The organic cation transporter 3 (Oct3) is a distinct catecholamine elimination pathway in adipocytes that mediate white adipose tissue formation. PLoS Biol 17 (1): e2006571. doi.org/10.1371/journal.pbio.2006571
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