In 1944, after the Nazis blocked supply lines, Holland suffered a famine that, naturally, affected that country’s pregnant women. As the war ended, newly born but underweight babies were able, at last, to have normal nutrition. But ultimately, all was not well. A follow-up years later found a high proportion of the “famine babies” had become obese adults suffering diabetes, hypertension and cardiovascular disease.
Psychiatry’s Kellie Tamashiro, in Hopkins’ Behavioral Neuroscience Lab, says that example has partly informed her research to understand what’s behind the tripling of obesity worldwide in the last 30 years. “Like the Dutch situation, some specific interplay of environment and behavior is at work. It has to be more than genes.”
Intuition says it’s basically behavior: Everybody knows people now eat more and exercise less. But that’s not as precise as translating a specific environmental factor or eating behavior into metabolic pathways gone wrong. And that, she explains, is where her studies are leading.
Tamashiro focuses on the effects of having less-than-optimal environments either in utero or just after birth. A solid body of animal research and human epidemiological studies suggest that such early problems create adults who avoid mirrors and populate hospitals. It’s called the Barker hypothesis: A bad early environment somehow sets metabolism to favor later obesity and diabetes.
Most existing research has centered on giving pregnant rats too-high or too-low nutrition. But Tamashiro has taken it a step beyond diet to factor in effects of added stress. She aims to reflect the human condition in inner cities where obesity is epidemic.
“In 1944,” Tamashiro explains, “the Dutch babies’ bodies were programmed to be more efficient than normal at saving energy.” Animal models shore this up: Short-changing maternal diet does indeed lead to obesity as pups mature. But the other extreme is true as well. An ultra-high energy diet during pregnancy also brings problems: In Tamashiro’s latest study, mother rats on fatty animal chow produced lardy pups at risk of abnormal adult metabolism.
That study helped clarify underlying physiology. Starting with pregnant rats fed high-fat chow, Tamashiro noted that as little as a month after birth, their fat pups—also high-calorie noshers—had the elevated levels of the leptin hormone that parallels onset of metabolic disease. And glucose intolerance that foreshadows diabetes had also begun.
But stress, she found, did the same thing—unsurprising, she says, because the neural pathways that regulate mammals’ stress responses are also active in guiding metabolic balance. So pregnant rats mildly upset by varying stressors such as bright lights or small quarters also have high-risk fat pups. It’s these early changes, she says, that may prime animals—or humans, perhaps—for later disease.
“Of course, it’s dangerous at this point to generalize to people,” Tamashiro adds, acknowledging her work as a step. “But it still lets us hope that intervening early in life could sidetrack disease.” For example, plump rat pups kept to a healthy diet, she found, see their sluggish metabolism even out. If future studies would lead to low-stress-pregnancy programs in inner cities or more enlightened infant formulas, all the better.