|
In a demonstration of estrogen's
role in controlling body weight and fat distribution, these adult
female rats both received surgery to induce post-menopausal
conditions. The smaller one received estrogen supplements
following surgery while the obese rat did not.
Image: Courtesy of Min Liu,
University of Cincinnati Academic Health Center |
This research seems to support a link between
estrogen and regulation of obesity, especially the dangerous
accumulation of abdominal fat linked to heart disease, diabetes, and
cancer, says Deborah J. Clegg, Ph. D., assistant professor of
psychiatry at the University of Cincinnati Academic Health Center, who
is directing the studies.
The findings may also help scientists develop more
targeted hormone replacement therapies, capable of stimulating
estrogen receptors in one part of the brain or body while dampening it
in the next, Clegg says.
Estrogen receptors are located on cells throughout
a woman�s body. Previous studies have shown that one type of estrogen
receptor, known as estrogen receptor alpha or ER-alpha, plays a role
in regulating food intake and energy expenditure. But scientists have
been unable to pinpoint exactly where these fat-regulating receptors
reside or how they work to govern these behaviors.
To determine the effect of dwindling estrogen
levels in the brain, Clegg and her colleagues are focusing on two
ER-alpha rich regions located in the hypothalamus, an area of the
brain that controls body temperature, hunger and thirst. The first
region, called the ventromedial nucleus or VMN, is a key center for
energy regulation.
Using a relatively new gene-silencing technique
called RNA interference, the researchers in earlier research
deactivated the alpha-receptors in the VMN. The estrogen receptors in
other regions of the brain maintained their normal capacity.
When estrogen levels in the VMN dipped, the animals�
metabolic rate and energy levels also plummeted. The findings show the
animals quickly developed an impaired tolerance to glucose and a
sizable weight gain, even when their caloric intake remained the same.
What�s more, the excess weight went straight to their middle sections,
creating an increase in visceral fat.
The findings suggested that the ER-alpha in this
region plays an essential role in controlling energy balance, body fat
distribution and normal body weight.
Clegg now plans to perform a similar experiment to
deactivate ER-alpha in the arcuate nucleus region of the hypothalamus.
This region contains two populations of neurons: one puts the brake on
food intake and the other stimulates food intake. Clegg anticipates
that a loss of estrogen in this region may create an increase in the
animals� appetites as well as their weight.
Clegg says her studies address an area that is
sorely needed given the incidence and impact of gender differences in
obesity and its complications.
�The accumulation of abdominal fat puts both men
and women at a heightened risk of cardiovascular disease, diabetes,
and insulin resistance,� she says. �Women are protected from these
negative consequences as long as they carry their weight in their hips
and saddlebags. But when they go through menopause and the body fat
shifts to the abdomen, they have to start battling all of these
medical complications.�
By identifying the critical brain regions that
determine where body fat is distributed, Clegg says her findings may
help scientists design hormone replacement therapies to better manage
and manipulate estrogen levels.
�If we could target those critical regions and
estrogen receptors associated with weight gain and energy expenditure,
we could perhaps design therapies that help women sidestep many of the
complications brought on by the onset of menopause,� she says. |
