Of mice and McDonald’s

Yale professor of neurobiology Tamas Horvath recently co-authored a paper examining the neurological link between the diet of mice during pregnancy and the tendency of their offspring to become obese. The study, which was published on Jan. 23 in the journal Cell, may help researchers develop novel ways to fight the obesity epidemic. The News sat down with Horvath to discuss maternal health, obesity, and how culture can change our brains.

Q. What exactly did you discover in your research?

A.We were interested in understanding how nutrition during pregnancy affects the development of the offspring’s brain and behavior in the long run. We exposed female mice to high-fat diets, and we found that those pups coming from the obese mothers were heavier. So our question was, what part of the development is affected by this change in feeding patterns?

We started to expose these mothers at different parts of pregnancy or post pregnancy to a high-fat diet, and found that the most important part of the interaction between the mother and the pup was during lactation. So if you gave a high fat diet to these mothers only during lactation, these pups became equally obese and diabetic [compared to] if the mother consumed a high-fat diet all the way through the pregnancy and lactation — that is the critical period. You don’t need to be necessarily obese — just eating this same type of food during this time could program the pup’s brain in a way that develops these maladaptations in metabolism. The period that we identified in mice — lactation — is occurring during the third trimester in humans, so if we want to apply the knowledge we learned from the mice to humans, then you would focus on [the third trimester], not necessarily the post-partum.

Q. So is our high-fat culture actually changing the way babies’ brains develop?

A. Correct. And this is a trans-generational impact that does not require genetics, or epigenetics, which is another popular way of describing these processes. It was kind of known and was well-established that obesity has a major genetic component — in fact a very high genetic component. Of course, not to the level of something like height, but we get some sort of connection. Nevertheless, genetics could not explain the obesity epidemic that supposedly had been emerging since the 60s. Because genetic material is the same, there must be some other pressures from the environment, or ways that propagate these obesity epidemics. This mechanism that we describe is potentially one that could explain how this is, because if you are obese you have a high fat or inappropriate diet during pregnancy, and you will deliver a child that will have a chance of developing metabolic disorders. And so these children eventually become mothers, and they create a child, and they are exposing this child again to an environment that will deliver the same outcome that they were exposed to by their mothers. If you can interfere in these future generations — or not interfere — somehow alter how mothers in general will be consuming food, you could perhaps reverse that epidemic, because the next generation will be healthier, and the generation after that. For us, in a way, the message from this kind of research is that you can develop methods to interfere with or reverse the epidemic.

Q. How exactly are the mice’s brains changing?

A. We connected how the brain communicates to tissues in the pancreas. The components of the brain that eventually lead to the alteration of the function of the beta cells of the pancreas, that are responsible for the insulin response to glucose, are changing under these conditions — how strong the connections, what type of connections are emerging. That we believe will be the key to these changes we found.

Q. Do you think research has revealed maternal behavior to be more important to the health of the child than previously thought?

A. Definitely — no question. I think that maternal behavior and in general maternal exposure to environment plays a very important role in determining how predisposed one is to later challenges in health and life. We did a paper last year which shows the same circuitry that is being affected by maternal [behavior] and seemingly causing this metabolic impairment — that same circuitry also takes a pivotal role during the same period of development in shaping other parts of the brain, not related to metabolism, but related to complex behaviors. You should anticipate the impacts of maternal diet that alters hypothalamic function could have impact on complex behaviors as well.

Q. What would you say prospective mothers should be eating during pregnancy?

A. Well, I think it is difficult to project long-term suggestions to people, but definitely I think that this research and other research suggests that it is very important to make sure that you have proper nutrition. Whatever [proper nutrition] means, it’s difficult to tell. But clearly it suggests that if you have metabolic problems, and you are pregnant, then you should be paying even more attention to what you eat in order for you to maximize the health of your child.

Q. What are your future directions for research?

A. I think it’s very important that these observations are confirmed for a human condition, [expanding] to other types of behaviors, [and] other types of tissue functions — how these early exposures to as diets could impact the general health, aging, and longevity.

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