Joslin Diabetes Center scientists have discovered a group of genes that govern the genesis of calorie-burning fat cells. This discovery may lead to novel ways to treat obesity in humans.
"With obesity at epidemic levels, finding new ways to treat it is one of medicine's holy grails," said C. Ronald Kahn, M.D., President of Joslin Diabetes Center, the Mary K. Iacocca Professor of Medicine at Harvard Medical School (HMS), and principal investigator of the study that appears in the June edition of the journal Nature Cell Biology. In laboratory studies of mouse cells, his research team identified genes that govern how precursor cells give rise to mature brown fat cells.
There are two main types of fat cells in the body -- white and brown. White fat cells are the "conventional" form of fat that we all recognize. They are designed to store energy for use in times of need. Chocked full of lipid droplets, these big cells accumulate under the skin and around internal organs.
By contrast, the main role of brown fat cells is to burn energy and generate heat. They contain small lipid droplets tucked between tiny energy factories called mitochondria. In mice, brown fat cells are found throughout the body and are present during the entire life cycle. In humans, they are principally found in the neck area of newborns, helping their tiny bodies generate heat. Brown fat cells largely disappear by adulthood, but their precursors still remain in the body, lodged in white-fat depots.
Because brown fat cells burn calories, Joslin scientists theorized that finding ways to encourage the development of brown fat might be good for treating obesity. In previous research, the scientists were among the first to develop cell lines of precursor cells that give rise to brown fat cells. "We used those cell lines to study how insulin affects the conversion of fat precursors, or preadipocytes, into mature brown adipocytes," said Yu-Hua Tseng, Ph.D., who with Atul J. Butte, M.D., Ph.D., of Boston's Children's Hospital and HMS, served as first author of the study. Others from Joslin's Cellular and Molecular Physiology research section who participated in the study included former Joslin fellows Efi Kokkotou, M.D., Ph.D., now at Beth Israel Deaconess Medical Center, and Vijay K. Yechoor, M.D., now at Baylor College of Medicine; Cullen M. Taniguchi, M.D., Ph.D., HMS student; Kristina M. Kriauciunas of Joslin; Joslin fellow Aaron M. Cypess, M.D., Ph.D.; Michio Niinobe, Ph.D., and Kazuaki Yoshikawa, M.D., Ph.D. of Osaka University, Japan; and Joslin Investigator Mary-Elizabeth Patti, M.D.
The researchers compared cell lines from normal "wild-type" mice to cells lines from mice that genetically lacked key components of the insulin-signaling network which are important to insulin's role in letting food nutrients enter the body's cells. If cells resist insulin, the body cannot get the energy it needs. This "insulin resistance" is the main culprit in the onset of in type 2 diabetes. Being overweight or obese has long been implicated with insulin resistance and type 2 diabetes and also raises the risk for heart disease, stroke and cancer.