Non-shivering thermogenesis
To understand how
non-shivering thermogenesis works, we need to take a step back and discuss
cellular respiration. The cells of our
body store energy from food in the chemical bonds of a molecule called
ATP. During cellular respiration, a cell
will convert glucose or fat into carbon dioxide, while slowly tapping into the
energy in those food molecules in order to make ATP. The final step of cellular respiration is
that the energy from the electrons in glucose are passed from protein to
protein, releasing energy that is used to pump protons into a membrane-bound
cellular space. You can think of these
protons as a form of potential energy, like stuffing a closet full of
balls. When you open up the closet door,
all the balls come tumbling out, releasing their potential energy in the
process. During cellular respiration,
this potential energy is used by an enzyme to make ATP. During non-shivering thermogenesis, though,
the potential energy stored in all those protons stuffed into a small space is
released by the cell as heat. Thus, the
energy from food is used to heat the body rather than being stored in ATP.
The main type of cell that
does non-shivering thermogenesis is brown adipocytes, or fat cells. Brown fat is very common in infants, but is
also found in adult humans in the upper chest and neck. The purpose of brown fat is to provide heat
for the body. Thus, non-shivering
thermogenesis is activated by a drop in body temperature. The cold temperature is sensed by the brain, which
activates the sympathetic nervous system (the “fight or flight” response),
which signals to the brown fat cells to express the genes necessary to bypass
ATP production and release heat instead.
In a recent paper published in PNAS,
Ye et al. describe how a different type of fat cell is able to skip all the
nervous system steps and sense the cold directly (red arrow in diagram). It is pretty cool that the fat cells are able
to sense temperature, as if they were neurons, and can act autonomously to remedy
the situation. No need for a brain here!
Independent thermogenesis
Through a series of
experiments, the authors demonstrate that a particular type of fat cell will
express genes necessary for non-shivering thermogenesis when exposed to cold,
independent of sympathetic nervous system activation.
In one experiment, they grew
fat cells at different temperatures and measured gene expression using a
technique called quantitative PCR (qPCR).
The idea behind this technique is that if a gene is highly expressed,
there will be a lot of mRNA in the cell (remember the “central dogma” of molecular
biology) and qPCR is a method for measuring the concentration of mRNA for a
particular gene. They focused their
measurements on thermogenic genes that are known to be part of the
non-shivering thermogenesis mechanism, such as Ucp1, which is the enzyme that
actually allows the protons to fall back across the membrane, thereby releasing
their energy as heat. They found that
these fat cells that were exposed to the cold expressed more Ucp1 mRNA, even in
the absence of any nervous system. These
are just cells in a dish, so this must be an intrinsic property of fat cells.
It wasn’t just any fat cell
that had this response. In fact, brown
adipocytes did not express more Ucp1 in the cold. It was a different type of fat cell called a
white adipocyte. What is white fat? The majority of fat in our body is white fat
and its purpose is to store fat for energy (for cellular respiration) and to
act as a thermal insulator, so we don’t lose as much heat through our skin. There is one subtype of white fat that has
been shown to do non-shivering thermogenesis and it was this type that could
express thermogenic genes, like Ucp1, in the cold, independent of the nervous
system.
Okay, so these white fat
cells don’t need input from the nervous system, but do they still use the same
intracellular pathway to turn on expression of these genes? Normally, when a fat cell is activated by the
sympathetic nervous system, it sets off a molecular cascade of events inside
the cell, which involves activation of molecules in a pathway called the cAMP
pathway (as shown in the diagram). The
authors inhibited this pathway in various ways and found that the cells could
still respond to the cold as before, so this effect must use a different
pathway.
There are still a number of
open questions, such as: how do fat cells sense temperature? Do they use the same types of receptors as
temperature-sensitive neurons? Why are
some white fat cells independent, but brown fat cells need the nervous system
to activate thermogenesis? One thing
that is clear, however, is that white fat cells are clearly important for
temperature regulation as well as fat storage.
The authors suggest that tapping into thermogenesis might be a good way
to help obese patients get rid of excess energy storage by releasing it as
heat. This pathway that is independent
of the sympathetic nervous system could allow medications to target only the
fat cells without involving the sympathetic nervous system which controls so
many other functions in the body.
Something to think about as
the cold Bay Area summer sets in.
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