New research published in the premier issue of Cell Metabolism finds that a single brain region is sufficient for normal control of blood sugar and activity level by the fat hormone leptin. The same region also exerts significant, though more modest, control over leptin's effects on body weight.
The findings in mice provide insight into potential mechanisms underlying type II diabetes and suggest new avenues for treatment, according to the researchers.
Secreted by fat cells, leptin signals the status of the body's energy content to the brain and is required for normal body weight and glucose balance. Mice lacking leptin develop obesity, diabetes, and inactivity, among other symptoms.
The new results suggest that leptin signaling acts directly on the brain region known as the hypothalamic arcuate nucleus (ARH) to control insulin and glucose levels in the bloodstream, report Joel Elmquist and Bradford Lowell, both of Beth Israel Deaconess Medical Center and Harvard Medical School, and their colleagues. ARH neurons also mediate the majority, if not all, of the hormone's action on locomotor activity, they found.
Leptin receptors in the ARH accounted for approximately 22 percent of the hormone's effects on body weight, the group reports, suggesting that other brain regions are also important to this hormonal function.
"As the incidence of obesity and diabetes continues to rise in industrialized countries, a clear understanding of the cellular and neuroanatomic pathways that control energy and glucose balance is critical to the discovery of new methods to prevent or treat these conditions," Elmquist said. "The current findings definitively demonstrate that the hypothalamic arcuate nucleus is required for normal body weight homeostasis and is sufficient to control leptin's anti-diabetic actions."
Using a novel technique, the researchers unilaterally re-activated leptin receptors in the ARH of mice in which they had otherwise blocked all leptin receptor activity. The ARH had been proposed as an important site of leptin action.
At 12 weeks of age, mice with restored receptor activity had an approximately 22 percent decline in total body weight due to a reduction in fat mass, compared to those lacking active leptin receptors, they found.