Overweight for three generations
Overfeeding of genetically normal newborn rats affects three generations. In addition to disturbances in the basic metabolic processes, the rate of reproduction is also affected. Some women who become glucose intolerant late in pregnancy may develop gestational diabetes: they are more likely to give birth to large children who are prone to obesity. According to a new study on genetically normal rats, it is conceivable that this effect of overeating can last for three generations. The findings could explain similar trends in human populations observed in Japan, Australia, the American Southwest and some Pacific islands.
The fact that the overfed animals did not have a genetic defect is crucial because it showed that developmental dietary conditions can affect later generations even in the absence of genetic disorders. These are the findings of a University of Washington working group presented on October 28, 1997 at the Society for Neuroscience Annual Meeting.
The newborn rats were overfed to simulate the dietary conditions of late human pregnancy that infants of diabetic mothers commonly encounter. Gestational diabetes occurs in two to three percent of otherwise normal human pregnancies. The maternal organism regulates the delivery of nutrients to the offspring via the bloodstream. However, pregnancy can put extra strain on the pancreas. In this case, it may no longer be able to produce enough insulin. However, this is necessary in order to utilize the carbohydrates that trigger gestational diabetes. If the carbohydrates remain in the blood, they can be made available as food for the child, who can then become overfed.
Elsie Taylor, a psychologist and researcher at the University of Washington, says that newborn rats are immature at birth. In their first three weeks of life, they could therefore be compared with human fetuses during the last three months of pregnancy in terms of brain development and metabolism.
Newborn rats are a godsend to developmental physiology, says Jaime Diaz, a psychologist at the University of Washington and Taylor's collaborator on the study. We can study newborn rats and learn a lot about maturation processes during late human pregnancy. Our experiments show that a short period of overfeeding results in a group of rats and their offspring that is distinctly different from their siblings and their offspring.
Our findings demonstrate that many effects observed in the offspring of diabetics can be caused by changes in the developmental environment, independent of genetic influences. So what results from overfeeding or diabetes more or less shapes the newborn for life adds Taylor.
Taylor and Diaz used only female rats for their studies. They focused their work on how overeating affects the maternal environment to which later generations are exposed. Instead of the usual white rats, they used black and white spotted Long Evans rats for the studies.
The first generation consisted of normal sibling rats that were randomly assigned to one of three groups at five days of age. The first group was fed by their mothers. The second was fed via a tube into the stomach with about the same amounts as the maternally reared animals. The third group was also fed via a tube into the stomach, but here the animals received 150% of the amounts that the comparison groups received. From the age of 15 days, groups two and three were again fed by their mothers. A week later, all animals were weaned, fed lab chow, and treated identically.
On day 15, the overfed rats weighed 20% more than the controls. However, during the maternal feeding period, the weight returned to normal. However, it increased again at puberty and when the animals were crossed with males at 4 months of age, they weighed 12% more than the control rats. Many animals from the overfed first generation had problems with subsequent pregnancy, and the birth rate was 70% of that in normal rats.
Body weight pattern reversed in the second generation. The offspring of the experimental animals were significantly smaller than those of the control group, although both groups were reared identically. "These rats were 5% smaller at birth and remained significantly smaller throughout their lives," reports Taylor. There were also reproductive problems: when this generation of experimental animals was crossed, the birth rate was only 57% of the control group.
Birth weight was the same in both groups in the third generation. However, the offspring of the original overfed group developed accelerated growth around the ninth day after birth and were 15% larger at three weeks after birth. In Taylor's opinion, the effect is significant in the third generation and could be repeated in a second cross series.
Taylor now hopes to study the metabolic changes in the overfed rats at different times, particularly during pregnancy. She wants to find out how regulatory mechanisms might have changed, including the hormones insulin and leptin in the brain.
The work has far-reaching clinical implications for understanding diabetes in pregnancy. It is also important for the treatment of obesity and non-insulin dependent diabetes in different peoples such as the Pima Indians of Arizona or the Aborigines of Australia. The diet of the Pima had changed when they moved to a reserve around the turn of the century. They currently have the highest rate of non-insulin dependent diabetes in the world. According to Taylor, 50% of Pima by age 35 have diabetes. In the space of a century, their basic body shape has changed, from thin to obese.
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