Offspring of animals fed extra fat show anxiety, memory deficits and food issues
WASHINGTON — There’s always new advice coming out about what pregnant women should — or should not — eat. Get enough protein. Get enough folate. Don’t eat too much sugar. But don’t go too low-carb. Don’t gain too much weight during pregnancy. Eat more nuts. Don’t drink. It’s enough to make any mom-to-be’s head spin.
Four different animal studies presented at the recent Society for Neuroscience meeting add another mandate to the list: High-fat diets during pregnancy could have sweeping effects on a female’s offspring.
Much of the science on high-fat diets begins in rodents. Salvatore Fusco and colleagues at the Catholic University of the Sacred Heart in Rome fed female mice diets of about 45 percent fat for four weeks before mating and for two weeks after their pups were born. Offspring of the high-fat-diet moms had deficits in memory compared with offspring of mouse moms that ate normal chow, the scientists reported at the meeting on November 18.
The mice had to swim to a platform in a memory task called a Morris Water Maze. After teaching the mice where the platform is, scientists cloud the water and remove the platform. They then measure how long the mouse spends in the area where the platform used to be. The offspring of mice fed the high-fat diet learned the task more slowly and spent less time near the platform’s location, a bad sign for memory.
Fusco’s group also showed that the effects on memory continued on to the next generation of mice, possibly due to epigenetic effects, chemical changes that turn genes off or on.
The effects of a diet high in fat may extend beyond memory. Staci Bilbo and colleagues at Duke University reported November 18 that a similar high-fat diet in mice caused pregnant moms to gain more weight, and their offspring showed higher anxiety and depression-like measures compared to the offspring of chow-fed moms.
For pregnant rats, a high-fat diet also seems to produce anxiety-like behavior in offspring, Sayuri Kojima and Linda Rinaman of the University of Pittsburgh reported November 17. And the male offspring of high-fat-fed rats were more anxious than their control-diet counterparts. The researchers traced these changes to a decrease in brain cells that release the hormone oxytocin in the hypothalamus, an area of the brain associated with food intake.
Oxytocin has many roles in social behaviors such as maternal care and those associated with anxiety. But it also decreases the amount of food a rodent eats. The scientists hypothesize that the change in oxytocin-releasing neurons could mean changes in food intake. “There is good literature to support the idea that oxytocin projections to the brainstem are an appetite suppressant,” says Hans-Rudolf Berthoud, a neurobiologist at Louisiana State University in Baton Rouge. But the effects of fewer oxytocin-releasing neurons in the hypothalamus remain unclear.
Studies in rats and mice sometimes get dismissed as being very far from the human conditions. But these findings aren’t limited to rodents. Heidi Rivera and colleagues at the Oregon National Primate Research Center in Beaverton gave a diet that was 37 percent fat to female monkeys for a full two years, during which the animals got pregnant, gave birth and nursed their babies. Offspring of the monkey moms on the high-fat diet ate more of a delicious high-fat and high-sugar food than the offspring of control-diet-fed mothers.
When Rivera examined the brains of the offspring, she found that monkeys whose mothers ate high-fat diets may have a reduced number of neurons that release the chemical messenger dopamine. These dopamine-releasing neurons come from reward-related brain structures such as the nucleus accumbens. They end in the prefrontal cortex, which plays an important role in decision-making. Rivera hypothesizes that fewer dopamine-releasing neurons mean reward is impaired, causing the offspring of high-fat diet moms to overeat tasty — and high calorie — foods.
Rivera’s findings support a hypothesis called the reward deficiency hypothesis, Berthoud says. “The idea is that the dopamine signaling system becomes reduced or numbed at some point,” he explains. “To make up for decreased dopamine signaling, you need more palatable food.” The effect is similar to drug tolerance, in which the more someone takes a drug such as cocaine, the more that is required to get a high.
Past studies of high-fat diets have yielded somewhat mixed results in rodents, says Ralph DiLeone, a neurobiologist at Yale University. “This is probably one of the first studies in primates where they’ve seen this kind of effect,” he notes. “It’s a big step toward humans.”
Together, the four studies all showed significant effects of a high-fat diet during pregnancy. But Margaret McCarthy, a neuroendocrinologist at the University of Maryland in Baltimore, notes in reference to Bilbo’s study that it is important to separate out the effects of the diet from the potential effects of weight gain. “You can get fat on a high-sugar diet as well as a high-fat diet,” she explains. “Is it the obesity? Or is it the food?” While some of the animals in these studies gained significant weight, others did not. It would also be important to find out if exercise counteracts any of the effects of a high-fat diet.
The high-fat diets in these studies were all between 37 and 45 percent fat. That might seem high for people, but Rivera says 37 percent fat is the Western diet norm. The 2010 U.S. dietary guidelines recommend diet between 25 and 35 percent fat for adults. But studies have shown that more than 90 percent of Americans exceed that recommended value. I checked my own nutrition values, which I track every day. Sure enough, my own diet averaged around 30 to 40 percent fat per day, and I’ve got a reputation for being a bit of a health nut.
While I’m now dubiously eyeing the fat content of my own diet with regard to my future progeny, many questions remain. The studies presented at the meeting address mice, rats and monkeys. But humans may not be the same. High-fat diets may be worse, or better, than high sugar or high-carb diets. Exercise may exacerbate some problems and mitigate others. And of course, every person is different, and their dietary needs will be different as well.
High-fat diets may indeed have long-term effects on offspring. The underlying causes remain to be understood. But finding the mechanism, and the role that mechanism plays in humans, might just place high-fat diets on the “don’t” list for moms-to-be.