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Joslin scientists have discovered a mechanism that
regulates the production of brown fat, a type of fat
which plays an important role in heat production and
energy metabolism. The findings, which appear in the
upcoming issue of Nature, may lead to new therapies
that increase BAT formation to treat obesity.
Two types of fat tissue are present in humans and
other mammals: white adipose tissue (WAT) or white
fat, which stores fat; and brown adipose tissue (BAT)
or brown fat, which burns fat to produce heat. Brown
fat also metabolizes glucose and fatty acids which
is important in diabetes and metabolic diseases.
Studies suggest that brown fat provides a natural
defense against obesity: people with greater
quantities of brown fat have lower body weights.
This has made brown fat the focus of considerable
interest among scientists and pharmaceutical
companies looking for ways to treat obesity.
Joslin scientists in the Tseng Laboratory of the
Section on Integrative Physiology and Metabolism
previously discovered that one type of bone
morphogenetic protein, BMP-7, plays a key role in
the control of brown fat formation and its
heat-producing activity, which regulates whole body
metabolism.
In the present study, the scientists created a
genetically mutant mouse model deficient in type 1A
BMP-receptor (BMPR1A), a key receptor for BMP-7
which has been shown to be associated with obesity
in human populations.
Mice have two types of BAT: constitutive BAT (cBAT),
which develops before birth; and recruitable BAT (rBAT),
which is found in WAT and skeletal muscle. Humans
may also have two types of BAT.
The mice lacking BMPR1A were born with a deficiency
of cBAT. Despite their lack of cBAT, the mutant mice
were able to “maintain their body temperature
perfectly,” says senior author Yu-Hua Tseng, Ph.D.,
Assistant Professor of Medicine at Harvard Medical
School, Principal Faculty of the Harvard Stem Cell
Institute and an Investigator in the Section on
Integrative Physiology and Metabolism.
The scientists discovered that when cBAT is
deficient, cBAT cells send a signal through the
sympathetic nervous system to increase production of
rBAT within white fat. This study is the first to
report this cross-talk between these two types of
brown fat. The increased rBAT was sufficient to
maintain normal body temperature and also protect
against diet-induced obesity: When the control and
mutant mice were fed a high-fat diet, the mutant
mice did not gain more weight than the control mice.
Until this study, it was not known why a body needs
two types of BAT and how they interact with each
other. “These results show us that brown fat is
essential for normal functioning. When one type of
brown fat is deficient, the body has a sophisticated
system for inducing development of the other type of
brown fat to maintain body temperature and
metabolism,” says Dr. Tseng.
The paper’s lead author is Tim Schulz, a
postdoctoral scientist in the Tseng Laboratory.
Other contributors include Tian Lian Huang, Ruidan
Xue, Lindsay McDougall, Kristy Townsend and Aaron
Cypess of Joslin; Yuji Mishina of the University of
Michigan; and Ping Huang and Emanuela Gussoni of
Children’s Hospital, Boston.
This study was funded by the National Institutes of
Health, the Eli Lilly Research Foundation and the
Harvard Stem Cell Institute.
See also
Newly isolated 'beige fat' cells could help fight
obesity (16/07/2012)
Turning 'bad' fat into 'good': A future treatment
for obesity? (04/05/2011)
For more information
Joslin Diabetes Center
Brown-fat paucity due to impaired BMP signalling
induces compensatory browning of white fat
(MDN)
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