NEW ORLEANS -- Research at the University at Buffalo is the first to provide a biochemical explanation for obesity that could help pave the way for development of treatments for the condition.
Mulchand S. Patel, Ph.D., professor and chair of the UB Department of Biochemistry, reported here today (Monday, April 7) that research with rat pups has shown that different tissues exhibit specific responses to hyperinsulinemia, the overproduction of insulin that occurs in obesity.
Unlike previous animal models in which both conditions occur simultaneously, the UB model is the first to demonstrate that chronic hyperinsulinemia precedes obesity.
Working with rat pups born to mothers who were hyperinsulinemic and obese, the UB researchers have measured the effect of chronic hyperinsulinemia on key enzymes in the insulin-signaling pathway.
"Our results show that in the presence of an overproduction of insulin, obesity develops because while the functional activity of the insulin-signal transduction pathway is decreased in liver and muscle tissue, its activity is increased in fatty tissue," said Patel. "This information provides a biochemical basis for the development of obesity and may make it possible one day to develop specific interventions for obesity."
Patel reported the results at Experimental Biology '97, the annual meeting of the Federation of American Societies for Experimental Biology. He conducted the work with Malathi Srinivasan, Ph.D., and Satyaprasad Vadlamudi, Ph.D., postdoctoral associates in biochemistry at UB.
Patel said the findings suggests the rat pups have an early metabolic setpoint, which programs them to overproduce insulin early in life and become obese later on.
Normally, insulin is produced by the pancreas in varying levels, depending on the amount of glucose in the blood.
But while in utero, the pancreatic cells of these offspring somehow are targeted to overproduce insulin by hormonal or environmental influences from the mothers, who are hyperinsulinemic and obese, said Patel.
"The pancreatic cells in the pups respond to the hyperinsulinemia in the mothers early on, and later in adult life, the body responds to the offspring's hyperinsulinemia," he continued.
"It's a big mystery as to how this happens because these second-generation animals experience no dietary modification," Patel said. He noted that the rat pups' only risk factor is that they were born to hyperinsulinemic mothers.
"In our study, second generation rats express hyperinsulinemia early in the post-weaning period, as their mothers did," stated Patel. "In spite of the fact that they were not eating a high-carbohydrate diet, the pups' metabolic setpoint may have a similar pattern to the mothers'."
The UB researchers now are trying to pinpoint exactly how early in their lives the rats begin to exhibit hyperinsulinemia and whether or not they are born with it.
This work builds on previous research by Patel that showed that diet-induced metabolic adaptations in the early stage of first-generation rats were transmitted to the second generation.