Obesity linked to altered appetite control center
Last Updated Aug 2007
Last Updated: 2007-03-06 15:48:26 -0400 (Reuters Health)
NEW YORK (Reuters Health) - Studies in obese mice suggest that a sensor in the
brain that normally detects the fat hormone leptin -- causing a series of events
that keep energy balance in check -- goes awry in the setting of obesity.
"Obesity is not a failure of will power, it is a biological failure. The brain is
not aware that the body is obese," Dr. Michael Cowley of Oregon Health and Science
University in Beaverton commented in a statement from Cell Press, which published
the research in the journal Cell Metabolism.
Leptin, which is secreted by fat cells, normally prevents overeating by affecting
brain cells that control appetite. However, high levels of leptin, which often
accumulate in obese people, can lead to leptin resistance, meaning the body no
longer responds to the hormone's appetite-suppressing signal.
The current research shows how a portion of the brain called the arcuate nucleus,
which is critically important for leptin sensing, is "negatively impacted by an
overabundance of leptin," explained Cowley.
For 20 weeks, Cowley and colleagues fed mice a high-fat or low-fat diet. Most, but
not all, of the animals in high-fat diet group became obese and developed symptoms
of diabetes, as is often the case in people. The low-fat diet group did not develop
these health problems.
Leptin levels in the obese mice, but not the lean mice, rose dramatically and the
obese animals, for the most part, became resistant to the weight-controlling
effects of leptin. Mice with diet-induced obesity failed to recognize "any element
of the leptin signaling cascade" that controls appetite, the authors report.
Importantly, the obese, leptin-resistant mice lost weight and regained their
sensitivity to leptin when the amount of fat in their diets was reduced. This was
a "nice surprise," Cowley said. "We had thought it might be more irreversible than
that."
These findings "strongly support" the case that reduced sensitivity to the fat
hormone leptin in critical brain regions is a cause of diet-induced obesity.
The research also supports prior studies, which have suggested that a protein
called SOCS-3 may be responsible for the loss of sensitivity to leptin. Therefore,
treatments designed to inhibit SOCS-3 may help thwart leptin resistance in cases of
obesity, perhaps restoring energy balance leading to weight loss, the investigators
offer.
SOURCE: Cell Metabolism, March 2007.
Dr. Sears Comment
Ultimately, the treatment of obesity will take place in the brain. It is the
balance of hunger and satiety that needs to be rebalanced. It has been shown that
high levels of triglycerides and elevated C-reactive protein inhibit leptin's
signaling ability to cause satiety. In addition, elevated levels of
endocannabanoids (derived from arachidonic acid) in the brain increase hunger.
High-dose fish oil can modify both parts of the equation and thus may provide the
key to long-term weight control.