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Researchers discover new Fat-Fighting
Pathway
Newswise — Researchers at Albert Einstein
College of Medicine of Yeshiva University
have discovered a process that controls the
amount of fat that cells store for use as a
back-up energy source.
Disruption of this process allows cellular
fat to accumulate — a key factor in
age-related metabolic diseases such as
obesity and type 2 diabetes.
The study is published in the online version
of Nature.
Discovery of this previously unknown
fat-fighting pathway could lead to novel
drugs for the treatment of metabolic
syndrome (characterized by obesity, blood
lipid disorders, and insulin resistance) and
for a common liver disease known as “fatty
liver” or steatohepatitis.
Nonalcoholic steatohepatitis (NASH) is a
common, often “silent” liver disease.
Although NASH resembles alcoholic liver
disease, it occurs in people who drink
little or no alcohol.
NASH affects 2 to 5 percent of Americans,
according to the National Institute of
Diabetes and Digestive and Kidney Diseases.
All cells store lipids, a type of fat, in
the form of small droplets that can be
broken down for energy when needed.
In situations of excessive food intake or in
certain diseases such as diabetes or
obesity, these lipid droplets become so
large that they interfere with normal cell
function.
“In this study, we found that the amount of
fat stored in these intracellular lipid
droplets is controlled through autophagy, a
process until now thought to help primarily
in digesting and recycling damaged cellular
structures,” says Mark Czaja, M.D.,
professor of medicine at Einstein whose team
worked collaboratively on the research with
the laboratory of Ana Maria Cuervo, M.D.,
Ph.D., associate professor of developmental
& molecular biology, medicine, and anatomy &
structural biology at Einstein.
Autophagy, or “self-eating,” is carried out
by lysosomes, which function as the cell’s
recycling center. In studies of liver cells
in culture and in live animals, Dr. Czaja
and his colleagues discovered that lysosomes
do something never before observed:
continuously remove portions of lipid
droplets and process them for energy
production.
“When food is scarce, autophagy becomes a
main source of energy for the cells and this
process of digesting lipid droplets is
accelerated,” says Dr. Cuervo.
“If autophagy slows down, as occurs in aging, the lipid droplets stored in
cells keep growing and eventually become so
big that they can no longer be degraded.”
This slowdown in fat control appears to
trigger a vicious cycle in which the
enlarging fat droplets impair autophagy,
allowing even more fat to accumulate, and so
on, which could eventually contribute to
diseases such as diabetes.
The researchers noted that therapies aimed
at helping autophagy operate more
efficiently might prevent disease by keeping
fat droplets under control.
Drs. Cuervo and Czaja’s paper, “Autophagy
regulates lipid metabolism” is published in
the April 1 online version of Nature. Their
co-authors at Einstein include Rajat Singh
and Susmita Kaushik (primary co-authors),
Yongjun Wang, Youqing Xiang, and Inna Novak;
as well as Masaaki Komatsu and Keiji Tanaka
of the Tokyo Metropolitan Institute of
Medical Science, Bunkyo-ku, Tokyo, Japan.
About Albert Einstein
College of Medicine of Yeshiva University
Albert Einstein College of Medicine of
Yeshiva University is one of the nation’s
premier centers for research, medical
education and clinical investigation.
It is the home to some 2,000 faculty
members, 750 M.D. students, 350 Ph.D.
students (including 125 in combined
M.D./Ph.D. programs) and 380 postdoctoral
investigators.
Last year, Einstein received more than $130
million in support from the NIH.
This includes the funding of major research
centers at Einstein in diabetes, cancer,
liver disease, and AIDS. Other areas where
the College of Medicine is concentrating its
efforts include developmental brain
research, neuroscience, cardiac disease, and
initiatives to reduce and eliminate ethnic
and racial health disparities.
Through its extensive affiliation network
involving five hospital centers in the
Bronx, Manhattan and Long Island – which
includes Montefiore Medical Center, The
University Hospital and Academic Medical
Center for Einstein – the College runs one
of the largest post-graduate medical
training program in the United States,
offering approximately 150 residency
programs to more than 2,500 physicians in
training. For more information, please visit
www.aecom.yu.edu.
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