A
report in the August issue of the Cell Press journal Cell Metabolism
might help to explain why it’s so frustratingly difficult to stick to a
diet. When we don’t eat, hunger-inducing neurons in the brain start
eating bits of themselves. That act of self-cannibalism turns up a
hunger signal to prompt eating.

   

“A
pathway that is really important for every cell to turn over components
in a kind of housekeeping process is also required to regulate
appetite,” said Rajat Singh of Albert Einstein College of Medicine.

   

The
cellular process uncovered in neurons of the brain’s hypothalamus is
known as autophagy (literally self-eating.) Singh says the new findings
in mice suggest that treatments aimed at blocking autophagy may prove
useful as hunger-fighting weapons in the war against obesity.

   

The
new evidence shows that lipids within the so-called agouti-related
peptide (AgRP) neurons are mobilized following autophagy, generating
free fatty acids. Those fatty acids in turn boost levels of AgRP, itself
a hunger signal.

   

When
autophagy is blocked in AgRP neurons, AgRP levels fail to rise in
response to starvation, the researchers show. Meanwhile, levels of
another hormone, called -melanocyte stimulating hormone, remain
elevated. That change in body chemistry led mice to become lighter and
leaner as they ate less after fasting, and burned more energy.

   

Autophagy
is known to have an important role in other parts of the body as a way
of providing energy in times of starvation. However, unlike other
organs, earlier studies had shown the brain to be relatively resistant
to starvation-induced autophagy.

   

“The
present study demonstrates the unique nature of hypothalamic neurons in
their ability to upregulate autophagy in response to starvation that is
consistent with the roles of these neurons in feeding and energy
homeostasis,” the researchers wrote.

   

Singh
said he suspects that fatty acids released into the circulation and
taken up by the hypothalamus as fat stores break down between meals may
induce autophagy in those AgRP neurons. Singh’s research earlier showed a
similar response in the liver.

   

On
the other hand, he says, chronically high levels of fatty acids in the
bloodstream, as happens in those on a high-fat diet, might alter
hypothalamic lipid metabolism, “setting up a vicious cycle of
overfeeding and altered energy balance.” Treatments aimed at the pathway
might “make you less hungry and burn more fat,” a good way to maintain
energy balance in a world where calories are cheap and plentiful.

   

The
findings might also yield new insight into metabolic changes that come
with age given that autophagy declines as we get older. “We already have
some preliminary evidence there might be changes with age,” Singh said.
“We are excited about that.”

SOURCE: http://www.cellpress.com/