Having a lower percentage of body fat may not always lower your risk for heart disease and diabetes, according to a study by an international consortium of investigators, including two scientists from the Institute for Aging Research of Hebrew SeniorLife, an affiliate of Harvard Medical School (HMS).
The Institute researchers, Douglas P. Kiel, M.D., M.P.H., and David Karasik, Ph.D., who are working with the Framingham Heart Study, identified a gene that is linked with having less body fat, but also with an increased risk of type 2 diabetes and heart disease, examples of so-called "metabolic diseases."
"We've uncovered a truly fascinating genetic story and, when we found the effect of this gene, we were very intrigued by the unexpected finding," says Dr. Kiel, a senior scientist at the Institute for Aging Research and a professor of medicine at HMS. "People, particularly men, with a specific form of the gene are both more likely to have lower percent body fat, but also to develop heart disease and type 2 diabetes. In simple terms, it is not only overweight individuals who can be predisposed for these metabolic diseases."
Reported online in the journal Nature Genetics on June 26, 2011, the investigators examined the genomes of more than 75,000 people to look for the genes that determine body fat percentage. They found strong evidence for a gene, called IRS1, to be linked with having less body fat. On further study, they found that this gene also leads to having unhealthy levels of cholesterol and blood glucose.
To understand why a gene that lowers body fat can be harmful, the scientists in the international consortium found that the gene lowers only the "subcutaneous" fat under the skin, but not the more harmful "visceral" fat that surrounds organs. The study authors speculate that people with this gene variant are less able to store fat safely under the skin and may, therefore, store fat elsewhere in the body, where it may interfere with normal organ function. All observations were more pronounced in men than in women and, indeed, many apparently lean men still carry too much abdominal fat.
"Genetic variants may not only determine the amount of total fat in your body," says Dr. Kiel, "but also what kind of fat you have. Some collections of fat, such as the kind located just under the skin, may actually be less harmful than the type located in the abdominal cavity, which may increase the risk of developing metabolic disease."
The effect, the researchers add, may be more pronounced in men due to the different body fat distributions between the sexes. Men store less fat than women, so they are more sensitive to changes in its distribution.
- Tuomas O Kilpeläinen, M Carola Zillikens, Alena Stančákova, Francis M Finucane, Janina S Ried, Claudia Langenberg, Weihua Zhang, Jacques S Beckmann, Jian'an Luan, Liesbeth Vandenput, Unnur Styrkarsdottir, Yanhua Zhou, Albert Vernon Smith, Jing-Hua Zhao, Najaf Amin, Sailaja Vedantam, So-Youn Shin, Talin Haritunians, Mao Fu, Mary F Feitosa, Meena Kumari, Bjarni V Halldorsson, Emmi Tikkanen, Massimo Mangino, Caroline Hayward, Ci Song, Alice M Arnold, Yurii S Aulchenko, Ben A Oostra, Harry Campbell, L Adrienne Cupples, Kathryn E Davis, Angela Döring, Gudny Eiriksdottir, Karol Estrada, José Manuel Fernández-Real, Melissa Garcia, Christian Gieger, Nicole L Glazer, Candace Guiducci, Albert Hofman, Steve E Humphries, Bo Isomaa, Leonie C Jacobs, Antti Jula, David Karasik, Magnus K Karlsson, Kay-Tee Khaw, Lauren J Kim, Mika Kivimäki, Norman Klopp, Brigitte Kühnel, Johanna Kuusisto, Yongmei Liu, Östen Ljunggren, Mattias Lorentzon, Robert N Luben, Barbara McKnight, Dan Mellström, Braxton D Mitchell, Vincent Mooser, José Maria Moreno, Satu Männistö, Jeffery R O'Connell, Laura Pascoe, Leena Peltonen, Belén Peral, Markus Perola, Bruce M Psaty, Veikko Salomaa, David B Savage, Robert K Semple, Tatjana Skaric-Juric, Gunnar Sigurdsson, Kijoung S Song, Timothy D Spector, Ann-Christine Syvänen, Philippa J Talmud, Gudmar Thorleifsson, Unnur Thorsteinsdottir, André G Uitterlinden, Cornelia M van Duijn, Antonio Vidal-Puig, Sarah H Wild, Alan F Wright, Deborah J Clegg, Eric Schadt, James F Wilson, Igor Rudan, Samuli Ripatti, Ingrid B Borecki, Alan R Shuldiner, Erik Ingelsson, John-Olov Jansson, Robert C Kaplan, Vilmundur Gudnason, Tamara B Harris, Leif Groop, Douglas P Kiel, Fernando Rivadeneira, Mark Walker, Inês Barroso, Peter Vollenweider, Gérard Waeber, John C Chambers, Jaspal S Kooner, Nicole Soranzo, Joel N Hirschhorn, Kari Stefansson, H-Erich Wichmann, Claes Ohlsson, Stephen O'Rahilly, Nicholas J Wareham, Elizabeth K Speliotes, Caroline S Fox, Markku Laakso, Ruth J F Loos. Genetic variation near IRS1 associates with reduced adiposity and an impaired metabolic profile. Nature Genetics, 2011; DOI: 10.1038/ng.866
Cite This Page: