Berkeley scientist says results could provide new
target for obesity research
Newswise, June 17, 2016 — A new
study is further burnishing copper’s reputation as an essential nutrient for
human physiology. A research team led by a scientist at the Department of
Energy’s Lawrence Berkeley National Laboratory (Berkeley Lab) and at the
University of California, Berkeley, has found that copper plays a key role in
metabolizing fat.
Long prized as a malleable,
conductive metal used in cookware, electronics, jewelry and plumbing, copper
has been gaining increasing attention over the past decade for its role in
certain biological functions. It has been known that copper is needed to form
red blood cells, absorb iron, develop connective tissue and support the immune
system.
The new findings, to appear in the
July print issue of Nature Chemical Biology but published online today, establishes for the first time
copper’s role in fat metabolism.
The team of researchers was led by
Chris Chang, a faculty scientist at Berkeley Lab’s Chemical Sciences Division,
a UC Berkeley professor of chemistry and a Howard Hughes Medical Institute investigator.
Co-lead authors of the study are Lakshmi Krishnamoorthy and Joseph Cotruvo Jr,
both UC Berkeley postdoctoral researchers in chemistry with affiliations at
Berkeley Lab.
“We find that copper is essential
for breaking down fat cells so that they can be used for energy,” said Chang.
“It acts as a regulator. The more copper there is, the more the fat is broken
down. We think it would be worthwhile to study whether a deficiency in this
nutrient could be linked to obesity and obesity-related diseases.”
Dietary copper
Chang said that copper could
potentially play a role in restoring a natural way to burn fat. The nutrient is
plentiful in foods such as oysters and other shellfish, leafy greens,
mushrooms, seeds, nuts and beans.
“Copper is not something the body
can make, so we need to get it through our diet,” said Chang. “The typical
American diet, however, doesn’t include many green leafy vegetables. Asian
diets, for example, have more foods rich in copper.”
But Chang cautions against ingesting
copper supplements as a result of these study results. Too much copper can lead
to imbalances with other essential minerals, including zinc.
Copper as a ‘brake on a brake’
The researchers made the copper-fat
link using mice with a genetic mutation that causes the accumulation of copper
in the liver. Notably, these mice have larger than average deposits of fat
compared with normal mice.
The inherited condition, known as
Wilson’s disease, also occurs in humans and is potentially fatal if left
untreated.
Analysis of the mice with Wilson’s
disease revealed that the abnormal buildup of copper was accompanied by lower
than normal lipid levels in the liver compared with control groups of mice. The
researchers also found that the white adipose tissue, or white fat, of the mice
with Wilson’s disease had lower levels of copper compared with the control mice
and correspondingly higher levels of fat deposits.
They then treated the Wilson’s
disease mice with isoproterenol, a beta agonist known to induce lipolysis, the
breakdown of fat into fatty acids, through the cyclic adenosine monophosphate
(cAMP) signaling pathway. They noted that the mice with Wilson’s disease
exhibited less fat-breakdown activity compared with control mice.
The results prompted the researchers
to conduct cell culture analyses to clarify the mechanism by which copper
influences lipolysis. The researchers used inductively coupled plasma mass spectroscopy (ICP-MS)
equipment at Berkeley Lab to measure levels of copper in fat tissue.
They found that copper binds to
phosphodiesterase 3, or PDE3, an enzyme that binds to cAMP, halting cAMP’s
ability to facilitate the breakdown of fat.
“When copper binds
phosphodiesterase, it’s like a brake on a brake,” said Chang. “That’s why
copper has a positive correlation with lipolysis.”
Hints from cows
The connection between copper and
fat metabolism is not altogether surprising. The researchers actually found
hints of the link in the field of animal husbandry.
“It had been noted in cattle that
levels of copper in the feed would affect how fatty the meat was,” said Chang.
“This effect on fat deposits in animals was in the agricultural literature, but
it hadn’t been clear what the biochemical mechanisms were linking copper and
fat.”
The new work builds upon prior
research from Chang’s lab on the roles of copper and other metals in
neuroscience. In support of President Barack Obama’s BRAIN
Initiative, Berkeley Lab provided Chang seed funding in 2013 through the
Laboratory Directed Research and Development program. Chang’s work continued
through the BRAIN Tri-Institutional
Partnership, an alliance with Berkeley Lab, UC Berkeley and UC San
Francisco.
Of the copper in human bodies, there
are particularly high concentrations found in the brain. Recent studies,
including those led by Chang, have found that copper helps brain cells
communicate with each other by acting as a brake when it is time for neural
signals to stop.
While Chang’s initial focus was on
the role of copper in neural communications, he branched out to investigations
of metals in fat metabolism and other biological pathways. This latest work was
primarily funded by the National Institutes of Health.