ORLANDO, Fla., January 11, 2013 – Men tend to store fat in the abdominal area, but don't usually have much in the way of hips or thighs. Women, on the other hand, are more often pear-shaped—storing more fat on their hips and thighs than in the belly. Why are women and men shaped differently? The answer still isn't clear, but it's an issue worth investigating, says Steven R. Smith, M.D., director of the Florida Hospital – Sanford-Burnham Translational Research Institute for Metabolism and Diabetes. That's because belly fat is associated with higher risks of heart disease and diabetes. On the other hand, hip and thigh fat don't seem to play a special role in these conditions.
In a study published in the Journal of Clinical Endocrinology and Metabolism, Smith and colleagues help explain this discrepancy by determining how belly and thigh fat differ genetically. This research might shift common thinking about fat—rather than focusing on how to banish belly fat, perhaps we need tip the balance in favor of heart-friendly fat in the lower body. In that case, the study also provides a first step toward aiming treatments at specific regions of the body, especially those that contribute most to the complications of obesity.
Belly fat genes vs. thigh fat genes
Smith and colleagues first took fat samples from men and women. Then they compared the genes most active in belly fat to those most active in thigh fat.
Here's what they found: The genes operating in a person's thigh fat are hugely different from those in his or her belly fat. For men, 125 genes are expressed differently in the belly than in the thighs. For women, it's 218 genes (most are unique to women, but 59 genes are the same as those that varied in male fat).
The most notable genes that differed are known as homeobox genes. These genes are known for their role in helping shape a developing embryo—determining which cells and organs go where. Many homeobox genes are influenced by hormones such as estrogen.
Why are these homeobox genes important for fat? "We believe these genes actually program those fat cells to respond differently to different hormones and other signals," Smith says.
Stem cells show fat is preprogrammed for its location
In the course of their work, Smith and his team also isolated stem cells from belly and thigh fat and grew them in laboratory dishes. This was a nice control because fat cells in a dish aren't influenced by nerves, hormones, or other outside signals.
Yet the researchers still saw the same location-specific differences in gene activity in the fat that developed from these stem cells. That result told them that the cells are preprogrammed. In other words, belly fat and thigh fat are genetically destined for their final location during development. It's not a difference that's acquired over time, as a result of diet or environmental exposure.
A new way of thinking about fat
Medically speaking, says Smith, it's important to understand these differences and how they arise. "Even though many women hate having large hips and thighs, that pear shape actually reduces their risk of heart disease and diabetes. In fact, women who have heart attacks tend to have more belly fat than thigh fat."
This research marks a new way of thinking. "Most people want to stop belly fat. But the problem is not just the fat—it's the location. Belly fat is just a marker of the problem. The real issue is in inability to store that fat on the hips and thighs," he continues.
Smith hopes that future studies aimed at understanding the fundamental differences in these fat depots could lead to specific treatments aimed at the regions that contribute most to the complications of obesity.
This research was funded by the U.S. National Institutes of Health (National Institute for Diabetes and Digestive and Kidney Diseases grants DK072476, R24DK087669, and P30DK46200), the Society for Women's Health Research Interdisciplinary Studies on Sex Differences (ISIS) Network on Metabolism, the Evans Center for Interdisciplinary Biomedical Research Affinity Research Collaborative on Sex Differences in Adipose Tissue at Boston University School of Medicine, the Genomics Core Facility at the Pennington Biomedical Research Center, and the Geriatric Research Education Clinical Center, Baltimore Veterans Affairs Medical Center.
The study was co-authored by Kalypso Karastergiou, Boston University; Susan K. Fried, Boston University; Hui Xie, Sanford-Burnham Medical Research Institute and the Translational Research Institute for Metabolism and Diabetes; Mi-Jeong Lee, Boston University; Adeline Divoux, Sanford-Burnham Medical Research Institute and the Translational Research Institute for Metabolism and Diabetes; Marcus A. Rosencrantz, University of California, San Diego; R. Jeffrey Chang, University of California, San Diego; and Steven R. Smith, Sanford-Burnham Medical Research Institute and the Translational Research Institute for Metabolism and Diabetes.
About Sanford-Burnham Medical Research Institute
Sanford-Burnham Medical Research Institute is dedicated to discovering the fundamental molecular causes of disease and devising the innovative therapies of tomorrow. The Institute consistently ranks among the top five organizations worldwide for its scientific impact in the fields of biology and biochemistry (defined by citations per publication) and currently ranks third in the nation in NIH funding among all laboratory-based research institutes. Sanford-Burnham utilizes a unique, collaborative approach to medical research and has established major research programs in cancer, neurodegeneration, diabetes, and infectious, inflammatory, and childhood diseases. The Institute is especially known for its world-class capabilities in stem cell research and drug discovery technologies. Sanford-Burnham is a U.S.-based, non-profit public benefit corporation, with operations in San Diego (La Jolla), California and Orlando (Lake Nona), Florida. For more information, news, and events, please visit us at sanfordburnham.org.
The Journal of Clinical Endocrinology & Metabolism