Australian scientists say they have unravelled a key mechanism in mice that may explain how obesity can be passed from a mother to her children.
The mechanism may also provide insight into why obese women find it difficult to fall pregnant.
According to their study, obese mothers 'transmit' metabolic problems to their offspring through changes to the mitochondria in their eggs, long before conception has taken place.
The researchers were able to reverse this damage in eggs of obese mice using drugs that reduce cellular stress.
They say their findings, published today in Development , may point towards future therapies to help obese women overcome fertility issues and prevent multigenerational health problems related to obesity.
Lead author and cell biologist Associate Professor Rebecca Robker from the Robinson Institute at the University of Adelaide was interested in why obese women have such trouble conceiving.
She found that not only do obese women not respond as well to fertility treatments, but their embryos seem to develop slightly differently, and they are more prone to miscarriages regardless of whether they conceive naturally or not; all of which suggested to her that there might be developmental problems with the early embryos.
"The thing that's really emerging now is that obese couples, their children also seem to have a propensity for obesity that's not explained by genetics," says Robker.
In their study, Robker and colleagues found big differences in the eggs of obese mice compared to those of lean mice; specifically, that the mitochondria — the energy producing components of a cell — are damaged, dysfunctional, and there are fewer of them.
"The mitochondria in the egg give rise to all of the mitochondria in the body of that offspring," Robker says.
"So we put those two pieces of information together and thought if the mitochondria in the egg are damaged, are they defective then in repopulating those cells of the embryo?"
They found the embryos of obese mice had less mitochondrial DNA in a whole range of tissues, from the heart, kidney, muscles and liver, even if those embryos were transplanted into a lean surrogate mother.
This could have lifetime consequences for the offspring's metabolic function, Robker says.
"Maybe in the muscle they would have less capacity to burn fat, maybe in the cardiac tissues as adults they would be less able to cope with a high fat diet, maybe in the kidney they would be less able to have optimal filtration [and] that could contribute to high blood pressure."
Reversing cellular stress
In exploring how obesity might affect the mitochondria, the team speculated that it might have something to do with stress to another cellular component known as the endoplasmic reticulum.
When researchers treated the obese mice with a drug known to reduce endoplasmic reticulum stress, they saw an increase in the mitochondrial DNA in their eggs, suggesting that this treatment offsetted the negative impact of obesity.
"These compounds were highly successful in preventing the stress response," she says. "Effectively the problem was fully reversed."
However, Robker emphasises it will be a long time before a treatment like this becomes a reality.
In the meantime, she urges women to take control of their health not just during pregnancy.
"Women often think 'I'm pregnant, I'll start being healthy now', but some signals have already been communicated to that egg, and nutrition has been stored in that egg since before conception."
Sources: http://www.abc.net.au/science/articles/2015/02/11/4177374.htm
The mechanism may also provide insight into why obese women find it difficult to fall pregnant.
According to their study, obese mothers 'transmit' metabolic problems to their offspring through changes to the mitochondria in their eggs, long before conception has taken place.
The researchers were able to reverse this damage in eggs of obese mice using drugs that reduce cellular stress.
They say their findings, published today in Development , may point towards future therapies to help obese women overcome fertility issues and prevent multigenerational health problems related to obesity.
Lead author and cell biologist Associate Professor Rebecca Robker from the Robinson Institute at the University of Adelaide was interested in why obese women have such trouble conceiving.
She found that not only do obese women not respond as well to fertility treatments, but their embryos seem to develop slightly differently, and they are more prone to miscarriages regardless of whether they conceive naturally or not; all of which suggested to her that there might be developmental problems with the early embryos.
"The thing that's really emerging now is that obese couples, their children also seem to have a propensity for obesity that's not explained by genetics," says Robker.
In their study, Robker and colleagues found big differences in the eggs of obese mice compared to those of lean mice; specifically, that the mitochondria — the energy producing components of a cell — are damaged, dysfunctional, and there are fewer of them.
"The mitochondria in the egg give rise to all of the mitochondria in the body of that offspring," Robker says.
"So we put those two pieces of information together and thought if the mitochondria in the egg are damaged, are they defective then in repopulating those cells of the embryo?"
They found the embryos of obese mice had less mitochondrial DNA in a whole range of tissues, from the heart, kidney, muscles and liver, even if those embryos were transplanted into a lean surrogate mother.
This could have lifetime consequences for the offspring's metabolic function, Robker says.
"Maybe in the muscle they would have less capacity to burn fat, maybe in the cardiac tissues as adults they would be less able to cope with a high fat diet, maybe in the kidney they would be less able to have optimal filtration [and] that could contribute to high blood pressure."
Reversing cellular stress
In exploring how obesity might affect the mitochondria, the team speculated that it might have something to do with stress to another cellular component known as the endoplasmic reticulum.
When researchers treated the obese mice with a drug known to reduce endoplasmic reticulum stress, they saw an increase in the mitochondrial DNA in their eggs, suggesting that this treatment offsetted the negative impact of obesity.
"These compounds were highly successful in preventing the stress response," she says. "Effectively the problem was fully reversed."
However, Robker emphasises it will be a long time before a treatment like this becomes a reality.
In the meantime, she urges women to take control of their health not just during pregnancy.
"Women often think 'I'm pregnant, I'll start being healthy now', but some signals have already been communicated to that egg, and nutrition has been stored in that egg since before conception."
Sources: http://www.abc.net.au/science/articles/2015/02/11/4177374.htm
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