Scientists use inactive, fat rats to study juvenile obesity

American Physiological SocietyJul 25 2012

Childhood obesity has nearly tripled in the past three decades, and by 2009, 17 percent of those 2-19 years of age were classified as obese. If actions against childhood obesity do not take place it is likely that today's children could be the first generation in over a century to experience a decline in life expectancy due to the epidemic of childhood obesity which leads to complications in later life. While little is known about how inactivity and obesity lead to undesirable side effects such as diabetes, cardiovascular disease and some cancers, scientists at the University of Missouri in Columbia have reviewed dozens of studies that look at childhood obesity using new animal models. The scientists suggest that the models could be key to better understanding the condition and its complex relationship to certain diseases.

The article is entitled "Potential Clinical Translation of Juvenile Rodent Inactivity Models to Study the Onset of Childhood Obesity." It appears in the online edition of the American Journal of Physiology - Regulatory, Integrative, and Comparative Physiology, published by the American Physiological Society.

Lead author Dr. Michael Roberts and his colleagues have written a review article outlining previous research, including some of their own studies, on various animal models that simulate childhood obesity through inactivity. The researchers concentrate specifically on a particular example, called the rodent wheel lock model, to study how different organ systems of young rats respond to a cessation of daily physical activity. This model houses rats in cages with running wheels starting at 28 days of age, which the animals voluntarily use for the next three to six weeks. After that period, the wheels are locked, preventing their primary source of physical activity.

Results

The researchers assert that findings from a variety of studies of juvenile obesity in humans show that children who are inactive in childhood are significantly more likely than those who engaged in exercise when young to continue this habit into adulthood. Additionally, they say, this inactivity in childhood initiates the mechanisms that lead to the consequences of obesity seen in adults. Using the wheel lock model and other animal models for studying childhood obesity is giving scientists more insight on exactly what happens when activity is restricted during youth, leading to obesity. For example, studies have shown that young, inactive rats have reduced insulin sensitivity (a precursor to type-2 diabetes), eat more and burn off fewer calories, and develop larger fat pads than animals who continue to exercise. Other studies show that fat cells multiply to a significantly greater extent in rats who aren't allowed to run on their wheels, while others show that such voluntary exercise in parents can stem positive transgenerational effects in offspring that are bred to be genetically predisposed to obesity (for instance, reduced body fat). Additionally, the wheel lock and other animal model suggest that exercise during youth may help preserve muscle mass over the course of aging and lower the activity of genes associated with cardiovascular disease.

The authors suggest that the wheel lock model and other models that allow exercise, then block it later, are akin to modern-day living conditions in which children who are active during the summer become increasingly sedentary when the school year starts. For these children, voluntary exercise abruptly ends when they must ride in motorized vehicles to school, sit in classrooms, and have insufficient recess or physical education classes. By studying these conditions in rats and other animals, Roberts and his colleagues say, researchers can avoid the ethical conundrum involved in forcing active children to refrain from exercise, imposing biopsies and other tissue sampling techniques, or other parts of research that are possible in animals but not in humans. However, the authors note that animal research still has a long way to go. They suggest that future studies incorporating animal models of childhood obesity take place over longer periods to determine how inactivity during youth contributes to adult consequences of obesity and whether interventions, such as reintroducing exercise, can affect this trajectory. They also note that future studies should examine whether restricting exercise during childhood could affect future motivation to exercise in adulthood, something preliminary work in their lab and others' has suggested.

"Continuing to examine the effects of inactivity on physiological homeostasis during youth is crucial given that 58 percent of children between the ages of 6-11 fail to obtain the recommended 60 minutes per day of physical activity and 92 percent of adolescents fail to achieve this goal," the authors say. "Importantly we contend that using juvenile rodent inactivity models will continue to provide a powerful clinical translational tool that can be used for primordial prevention of human childhood obesity."