Girk4 Gene May Hold the Key to Why Obesity Increases
with Age
Mice missing this gene develop obesity finds
University of Minnesota study
Read about part of brain that controls hunger - below story
June 10, 2008 – The likelihood of developing
obesity more than doubles between the ages of 20 and 60, as most senior
citizens know. But, why? That is the unanswered question that
researchers hope to answer with the discovery of a gene that may hold
the secret.
The research was published today in the Proceedings
of the National Academy of Sciences.
Researchers in the lab of Kevin Wickman, Ph.D.,
associate professor of pharmacology at the University of Minnesota
Medical School, removed a single gene from mice as part of an ongoing
study to understand how the brain controls heart function. After the
removal these mice did show some cardiac deficiencies but the
researchers also unexpectedly found that these mice now exhibited a
predisposition to adult-onset obesity.
"This was not an outcome we expected, but now we
have an animal model that may provide new insight into human obesity,"
said Wickman, co-author of the article.
By examining closely where this gene, termed Girk4,
is expressed in the body, the researchers found particularly high levels
in the hypothalamus, a brain region involved in regulating food intake
and energy expenditure. (Read more below story about hykpothalamus.)
Wickman speculated that disruption of normal
function in the hypothalamus may underlie the obesity seen in the mutant
mice, but he acknowledges that more research is needed to understand
where and how this gene works, and consequently, why mice missing this
gene develop obesity.
The age-dependence of the obesity seen in this
mouse model mimics human obesity patterns, researchers said. Indeed, the
likelihood of people developing obesity more than doubles between the
ages of 20 and 60.
"This is a novel finding that may provide important
new insight to the underlying cellular mechanisms that influence
obesity," said Catherine Kotz, Ph.D., co-author of the article,
scientist at the Minneapolis VA Medical Center and adjunct professor in
the Department of Food Science and Nutrition at the University of
Minnesota.
This research was funded by the University of
Minnesota Graduate School, a pilot award from the Minnesota Obesity
Consortium, and a grant from the National Institutes of Health. The
research was conducted in collaboration with the Department of Veterans
Affairs.
Brain's
Hypothalamus Controls Many Things Including Hunger
The
hypothalamus links the nervous system to the endocrine system via the
pituitary gland (hypophysis). The hypothalamus is located below the
thalamus, just above the brain stem. In humans, it is roughly the size
of an almond.
The hypothalamus is responsible for certain
metabolic processes and other activities of the Autonomic Nervous
System. It synthesizes and secretes neurohormones, often called
hypothalamic-releasing hormones, and these in turn stimulate or inhibit
the secretion of pituitary hormones.
The hypothalamus controls body temperature, hunger,
thirst, fatigue, anger, and circadian cycles.
Controls food intake
The extreme lateral part of the ventromedial
nucleus of the hypothalamus is responsible for the control of food
intake. Stimulation of this area causes increased food intake. Bilateral
lesion of this area causes complete cessation of food intake. Medial
parts of the nucleus have a controlling effect on the lateral part.
Bilateral lesion of the medial part of the ventromedial nucleus causes
hyperphagia and obesity of the animal. Further lesion of the lateral
part of the ventromedial nucleus in the same animal produces complete
cessation of food intake.
