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If you're serious about losing weight, you've got to watch
what you eat.
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simple calculator.
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It's not only how but also when that is important when
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Chemical Blocks Weight Gain
A natural brain substance has been found to block weight gain.
American researchers said mice with increased levels of the chemical
orexin did not gain weight when fed a high-fat diet.
The researchers at UT Southwestern Medical Center said orexin worked
by increasing the body’s sensitivity to the weight-loss hormone leptin.
Dr. Masashi Yanagisawa, senior author of the study and a professor of
molecular genetics at UT Southwestern, said boosting orexin levels may
prove useful as a therapy against obesity.
“Obese people are not deficient in leptin,” Dr. Yanagisawa said. “They
have tons of leptin floating around. The problem is that their brain isn’t
very sensitive to it.”
Dr Yanagisawa, who discovered orexin nearly 10 years ago, says the
chemical is involved in controlling appetite and sleep. Reduced levels of
orexin were found to lead to the sleep disorder narcolepsy in both rodents
and humans.
Orexin, which Dr. Yanagisawa discovered about a decade ago, is involved
in controlling appetite and sleep. He found that reduced levels of orexin
lead to the sleep disorder narcolepsy in both rodents and humans.
Orexin can boost the appetite in the short term, but, paradoxically, a lack of
orexin leads to obesity in the long run. “It’s been confusing,” said Dr.
Yanagisawa, an investigator with the Howard Hughes Medical Institute at
UT Southwestern.
Part of the confusion comes about because orexin acts on two different
molecules in the brain, OX1R and OX2R. In the current study, the
researchers aimed to distinguish which action was involved in weight
control.
The researchers increased the levels of orexin in mice, either through
genetic engineering or by administering the hormone into the brain.
When these mice were fed a healthy diet, the increased levels of orexin
made little difference in their weights compared to normal mice; however,
when the mice were fed a high-fat diet, the high-orexin mice remained
lean while the normal animals became obese. This difference was due to
an increase in the rate of metabolism – high-orexin mice burned fuel up to
20 percent faster than normal mice.
The high-orexin mice had lower blood levels of leptin, implying that the
leptin was more effective in controlling weight in these mice. In addition,
when the researchers administered leptin to the high-orexin mice, the
animals responded with a much greater loss of appetite and weight
compared to normal mice given leptin.
The researchers also administered a substance that activates only OX2R
to separate out orexin’s possible double action. The mice given this
substance showed the same beneficial response to high-fat diets and
leptin, confirming that OX2R controls the interaction.
These results clarify the action of orexin and point to OX2R as a potential
route to help treat obesity, but any practical use is still far off, Dr.
Yanagisawa said.
A primary hurdle to orexin-based drug development is a defense system
in the body called the blood-brain barrier, which prevents many
substances in the blood from penetrating into the brain. Because of this,
orexin cannot reach the brain when it is given orally or as an intravenous
or subcutaneous injection.
“Fortunately, however, high-orexin mice show no sleep/wake disturbance
or other serious side effects,” Dr. Yanagisawa said.
“This study suggests that if we can develop a compound that mimics the
action of orexin on its receptor, we might be able to treat narcolepsy and
other sleep disorders, as well as obesity,” Dr. Yanagisawa said. “We have
already screened out some such ‘orexin mimics.’
The next step is to do serious medicinal chemistry to make variations of
these compounds to get them more potent and specific. If we could
advance to early clinical trials in five years, I’d say we’d be lucky.
“I hope that in the long run a suitable orexin mimic might help people be
more mentally productive during the day, as well as be able to lose weight
more easily.”
The study appears in the journal Cell Metabolism.
A natural brain substance has been found to block weight gain.
American researchers said mice with increased levels of the chemical
orexin did not gain weight when fed a high-fat diet.
The researchers at UT Southwestern Medical Center said orexin worked
by increasing the body’s sensitivity to the weight-loss hormone leptin.
Dr. Masashi Yanagisawa, senior author of the study and a professor of
molecular genetics at UT Southwestern, said boosting orexin levels may
prove useful as a therapy against obesity.
“Obese people are not deficient in leptin,” Dr. Yanagisawa said. “They
have tons of leptin floating around. The problem is that their brain isn’t
very sensitive to it.”
Dr Yanagisawa, who discovered orexin nearly 10 years ago, says the
chemical is involved in controlling appetite and sleep. Reduced levels of
orexin were found to lead to the sleep disorder narcolepsy in both rodents
and humans.
Orexin, which Dr. Yanagisawa discovered about a decade ago, is involved
in controlling appetite and sleep. He found that reduced levels of orexin
lead to the sleep disorder narcolepsy in both rodents and humans.
Orexin can boost the appetite in the short term, but, paradoxically, a lack of
orexin leads to obesity in the long run. “It’s been confusing,” said Dr.
Yanagisawa, an investigator with the Howard Hughes Medical Institute at
UT Southwestern.
Part of the confusion comes about because orexin acts on two different
molecules in the brain, OX1R and OX2R. In the current study, the
researchers aimed to distinguish which action was involved in weight
control.
The researchers increased the levels of orexin in mice, either through
genetic engineering or by administering the hormone into the brain.
When these mice were fed a healthy diet, the increased levels of orexin
made little difference in their weights compared to normal mice; however,
when the mice were fed a high-fat diet, the high-orexin mice remained
lean while the normal animals became obese. This difference was due to
an increase in the rate of metabolism – high-orexin mice burned fuel up to
20 percent faster than normal mice.
The high-orexin mice had lower blood levels of leptin, implying that the
leptin was more effective in controlling weight in these mice. In addition,
when the researchers administered leptin to the high-orexin mice, the
animals responded with a much greater loss of appetite and weight
compared to normal mice given leptin.
The researchers also administered a substance that activates only OX2R
to separate out orexin’s possible double action. The mice given this
substance showed the same beneficial response to high-fat diets and
leptin, confirming that OX2R controls the interaction.
These results clarify the action of orexin and point to OX2R as a potential
route to help treat obesity, but any practical use is still far off, Dr.
Yanagisawa said.
A primary hurdle to orexin-based drug development is a defense system
in the body called the blood-brain barrier, which prevents many
substances in the blood from penetrating into the brain. Because of this,
orexin cannot reach the brain when it is given orally or as an intravenous
or subcutaneous injection.
“Fortunately, however, high-orexin mice show no sleep/wake disturbance
or other serious side effects,” Dr. Yanagisawa said.
“This study suggests that if we can develop a compound that mimics the
action of orexin on its receptor, we might be able to treat narcolepsy and
other sleep disorders, as well as obesity,” Dr. Yanagisawa said. “We have
already screened out some such ‘orexin mimics.’
The next step is to do serious medicinal chemistry to make variations of
these compounds to get them more potent and specific. If we could
advance to early clinical trials in five years, I’d say we’d be lucky.
“I hope that in the long run a suitable orexin mimic might help people be
more mentally productive during the day, as well as be able to lose weight
more easily.”
The study appears in the journal Cell Metabolism.
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