Fat tissue can be white, brown, or beige, differing
not only in color but also in metabolism. White fat
is principally a storage tissue, with a low rate of
metabolism; brown fat tissue, on the other hand, is
rich in mitochondria, and burns up stored fat,
releasing heat to warm the body, a process called
thermogenesis. After prolonged cold exposure,
brown-like fat cells develop within white fat,
making it beige, and beige fat cells also burn fat
to keep the body warm. A key stimulus for
thermogenesis is the hormone norepinephrine, which
exerts its effects at the cell surface, and is then
taken up into the cell and degraded to prevent
overstimulation. A mechanism for the uptake of
norepinephrine from fat cells has previously been
described, but its rate of uptake is relatively low,
suggesting 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 organic
cation transporter 3 (Oct3), which can import
norepinephrine into the cells for degradation. The
authors showed that reducing the level of Oct3, and
thus slowing norepinephrine degradation, 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 beige fat
content faster than their littermate controls,
accompanied by increased activity of thermogenic and
mitochondrial biogenic genes. Gratifyingly, when
looked at human genetic association databases, the
authors found that possessing versions of the OCT3
gene that make OCT3 protein with a reduced transport
function was associated with a higher metabolic
rate. Together, these results indicate that OCT3
plays an important role in regulating the rate of
beige fat production and thermogenesis in both mice
and humans. |