Still early days and a long way from a safe drug protocol, however we
are learning how to convert white fat cells into brown fat cells.
This is good news that should allow superior fat loss protocols that
work safely to limit accumulation through exercise. It has been far
too easy for the body to retain fat while also improving in fitness.
At least we understand that conversion is possible and even
inducible.
In the meantime, we get to wait.
Study Finds
Mechanism That Turns White Fat Into Energy-Burning Brown Fat Raises
Hopes for New Obesity and Diabetes Treatments
Released: 7/30/2012
4:50 PM EDT
Raises hopes for new
obesity and diabetes treatments
Newswise — New York,
NY (August 2, 2012) — Columbia University Medical Center (CUMC)
researchers have identified a mechanism that can give energy-storing
white fat some of the beneficial characteristics of energy-burning
brown fat. The findings, based on studies of mice and of human fat
tissue, could lead to new strategies for treating obesity and type 2
diabetes. The study was published today in the online edition of the
journal Cell.
Humans have two types
of fat tissue: white fat, which stores excess energy in the form of
triglycerides, and brown fat, which is highly efficient at
dissipating stored energy as heat. Newborns have a relative abundance
of brown fat, as protection against exposure to cold temperatures.
In adults, however, almost all excess energy is stored as white fat.
“Turning white fat
into brown fat is an appealing therapeutic approach to staunching the
obesity epidemic, but it has been difficult to do so in a safe and
effective way,” said study leader Domenico Accili, MD, professor of
Medicine and the Russell Berrie Foundation Professor at CUMC.
White fat can be
“browned” with a class of drugs called thiazolidazines (TZDs),
which increase the body’s sensitivity to insulin. However, TZDs
have many adverse effects — including liver toxicity, bone loss,
and, ironically, weight gain — which have limited the use of these
drugs.
The current study was
undertaken to learn more about the function of TZDs, with the
ultimate goal of developing better ways to promote the browning of
white fat.
Scientists have known
that TZDs promote the browning of white fat by activating a cell
receptor called peroxisome proliferator-activated receptor–gamma
(ppar-gamma), but the exact mechanism was not clear. To learn
more, Dr. Accili and his colleagues studied a group of enzymes called
sirtuins, which are thought to affect various biological processes,
including metabolism.
The researchers had
previously shown in mice that when sirtuin activity increases, so
does metabolic activity. In the present study, they found that
sirtuins boost metabolism by promoting the browning of white fat.
“When we sought to identify how sirtuins promote browning, we
observed many similarities between the effect of sirtuins and that of
TZDs,” said lead author Li Qiang, PhD, associate research
scientist in Medicine at CUMC.
Sirtuins work by
severing the chemical bonds between acetyl groups and proteins, a
process known as deacetylation. “So the next question was whether
sirtuins remove acetyl groups from ppar-gamma and, indeed, that was
what we found,” said Dr. Qiang.
To confirm that the
deacetylation of ppar-gamma is crucial to the browning of fat, the
researchers created a mutant version of ppar-gamma, in effect
mimicking the actions of sirtuins. The mutation promoted the
development of brown fat–like qualities in white fat.
“Our findings have
two important implications,” said Dr. Accili. “First, they
suggest that TZDs may not be so bad — if you can find a way to
tweak their activity. Second, one way to tweak their activity is by
using sirtuin agonists — that is, drugs that promote sirtuin
activity.”
“The truth is,
making sirtuin agonists has proved to be a real bear — more promise
than fact,” he continued. “But now, for the first time, we
have a biomarker for good sirtuin activity: the deacetylation of
ppar-gamma. In other words, any substance that deacetylates
ppar-gamma should in turn promote the browning of white fat and have
a beneficial metabolic effect.”
Dr. Accili’s paper
is titled, “Brown Remodeling of White Adipose Tissue by
SirT1-Dependent Deacetylation of Ppar-gamma.” The other
contributors are Ning Kon (CUMC), Wenhui Zhao (CUMC), Sangkyu Lee
(University of Chicago, Chicago, Illinois), Yiying Zhang (CUMC),
Michael Rosenbaum (CUMC), Yingming Zhao (University of Chicago), Wei
Gu (CUMC), and Stephen R. Farmer (Boston University School of
Medicine, Boston, Mass.)
This research was
supported by grants from the National Institutes of Health (HL087123,
DK58282, DK64773, DK063608, and RR024156).
The authors declare no
financial or other conflicts of interest.
Columbia University
Medical Center provides international leadership in basic,
pre-clinical and clinical research, in medical and health sciences
education, and in patient care. The medical center trains future
leaders and includes the dedicated work of many physicians,
scientists, public health professionals, dentists, and nurses at the
College of Physicians and Surgeons, the Mailman School of Public
Health, the College of Dental Medicine, the School of Nursing, the
biomedical departments of the Graduate School of Arts and Sciences,
and allied research centers and institutions. Established in 1767,
Columbia's College of Physicians and Surgeons was the first
institution in the country to grant the M.D. degree and is among the
most selective medical schools in the country. Columbia University
Medical Center is home to the largest medical research enterprise in
New York City and State and one of the largest in the United States.
Upon its official
opening in October 1998, the Naomi Berrie Diabetes Center at Columbia
University Medical Center established a new standard of care for the
1.6 million people with diabetes in the New York area—combining
world-class diabetes research and education programs with
unprecedented family-oriented patient care. Named for the mother of
the late Russell Berrie, founder of RUSS™ Toys, the center is today
recognized as the most comprehensive diabetes research and treatment
center in the tri-state region and has been designated a national
“Diabetes Center of Excellence” – one of only three in the
state of New York. Approximately one hundred faculty and students,
affiliated with the Center, conduct basic and clinical research
related to the pathogenesis and treatment of all forms of diabetes
and its complications. For more information, visit
www.nbdiabetes.org.
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