News & Research

By: Almas Eftekhari

The hypothalamus is a central region of the brain that has shown to play an important role in key metabolic functions, such as regulation of food intake, appetite, and body weight. Research funded by the American Diabetes Association provides a novel understanding of how this area of the brain and special cell types control blood sugar levels -- completely independent of food consumption and body fat.

Joel Elmquist, DVM, PhD and fellow Jong-Woo Sohn, PhD, of the University of Texas Southwestern Medical Center, studied the way two unique hormones, leptin (which comes from fat cells) and insulin (which comes from the pancreatic beta cells), work together inside the hypothalamus to affect energy balance and blood glucose levels. Dr. Elmquist's research provides clues to female fertility and how type 2 diabetes can develop in the absence of obesity.

Leptin signals the brain to suppress appetite and increase the body's use of energy, while insulin triggers fat cells to store fat. A former study at Dr. Elmquist's institution demonstrated that a single injection of leptin can treat fatally ill rodents with type 1 diabetes. While aiming to expand upon this result, Elmquist discovered that when the activity of both insulin and leptin is hindered in the brain of mice, insulin resistance and severe diabetes occur despite a healthy weight.

The research suggests that if confirmed in humans, even non-obese individuals may develop type 2 diabetes as a result of these hormone abnormalities. "Many people, and even many physicians, think you develop diabetes that is solely secondary to obesity. Our findings indicate that is not necessarily the case, at least in mice," said Dr. Elmquist, senior author of the study, published online in the April 7, 2010 issue of Cell Metabolism. "We can make the animals very diabetic without obesity."

The experiment also demonstrated reduced fertility in female mice when the same hormone abnormalities were present. Caused by a surge in male sex hormones, like testosterone, the mice experienced lower rates of pregnancy and bred smaller litters. This observation is similar to the characteristics of women affected by polycystic ovary syndrome (PCOS), a metabolic disorder that is often associated with obesity, diabetes, and heart disease. Although this finding was unexpected, Dr. Elmquist feels that his discovery may possibly be a new and unique genetic model of PCOS.

Drs. Elmquist and Sohn hope that their research efforts will lead to healthier management of blood glucose levels, as well as improved reproductive function in affected women. "These studies will not only advance the understanding about how the brain integrates various signals to maintain the energy and glucose balance, they may also facilitate the development of new drugs to decrease the prevalence of obesity and diabetes," Dr. Elmquist concluded.

(Hill JW, Elias CF, Fukuda M, Williams KW, Berglund ED, Holland WL, Cho YR, Chuang JC, Xu Y, Choi M, Lau zon D, Lee CE, Coppari R, Richardson JA, Zigman JM, Chua S, Scherer PE, Lowell BB, Bruning JC, Elmquist JK. Direct insulin and leptin action on pro-opiomelanocortin neurons is required for normal glucose homeostasis and fertility. Cell Metabolism. 2010 Apr 7; 11(4):286-297.)