Scientists Find Hormone Critical to Weight Loss in Mice
By Taking Away A Hormone, Fat Mice Become Trim
BOSTON — December 15, 1998 — Research by scientists at Joslin Diabetes Center and Beth Israel Deaconess Medical Center in Boston have found that when a hormone, known in short as MCH, is absent in laboratory mice, the mice eat less, burn more energy and weigh less compared to animals with the hormone.
In a report appearing in this week's journal Nature, Joslin researcher Eleftheria (Terry) Maratos-Flier, M.D., and BI-Deaconess researcher Jeffrey S. Flier, M.D., and their colleagues found that when melanin-concentrating hormone (MCH) was lacking in genetically-altered mice, the mice are thin.
"The mice without the gene for producing MCH had a reduced appetite and ate less. They also had an increased metabolic rate, which led to a 25 percent lower body weight," Dr. Maratos-Flier said. "Their fat deposits were reduced 50 percent over the control group." Dr. Maratos-Flier, an expert in appetite regulation and obesity, is an Investigator at Joslin and Assistant Professor of Medicine at Harvard Medical School. Dr. Jeffrey Flier, also an obesity and diabetes specialist, is Chief of Endocrinology and Vice Chairman of Medicine at Beth Israel Deaconess Medical Center and Professor of Medicine at HMS.
For some time, researchers at Joslin and BI-Deaconess and elsewhere have been studying the roles of various neuropeptides (hormones produced in the brain that influence neural activity) in obesity in mice. Most recently, Joslin researchers discovered that one strain of fat mouse, ob/ob, had high levels of MCH in the brain and that MCH increased eating in laboratory animals.
Obesity is closely linked to the onset of type 2 diabetes, the most common metabolic disease in humans. Type 2 (or adult-onset) diabetes affects an estimated 16 million people in the U.S. alone, one-third of whom don't know they have the disease. Type 2 diabetes is more common in people over age 40 who are obese, sedentary and have family members with the disease. Diabetes is the leading cause of adult-onset blindness, leg and foot amputations, and kidney disease, and is a major factor in heart disease and stroke.
"The thin mouse we have developed is believed to be the first lean mouse resulting from deletion of a neuropeptide or neuropeptide receptor," Dr. Flier said. At 17 weeks, the mice weighed about 25 percent less than control mice and had 50 percent less total body fat (were leaner) than the control animals. In addition, the mice ingested 12 percent fewer calories and, when food deprived, lost more weight than control mice over a 24-hour period. In addition, the mice lacking MCH appeared to have normal health, fertility, longevity and activity, the researchers reported.
"Further studies of MCH-deficient mice will be necessary to determine the exact role of MCH in different syndromes of obesity," Dr. Maratos-Flier said. Perhaps one day this discovery of the role of MCH in obesity may lead to an effective treatment for obesity in humans, but more research needs to be done," she said.
Established in 1898, Joslin Diabetes Center in Boston is an internationally recognized leader in diabetes and endocrine disease treatment, research, and patient and professional education affiliated with Harvard Medical School. In addition to its headquarters in Boston's Longwood Medical Area, Joslin has affiliated treatment centers across the country.
Beth Israel Deaconess Medical Center is a major clinical teaching and research affiliate of Harvard Medical School.
