SAN ANTONIO, Texas (June 5, 2014) -- Scientists this week reported that a molecular pathway called mTORC1 controls the conversion of unhealthy white fat into beige fat, an appealing target for increasing energy expenditure and reducing obesity. The team, led by researchers from the School of Medicine at The University of Texas Health Science Center at San Antonio, also found that a protein, Grb10, serves as the on-off switch for mTORC1 signaling and the "beigeing" of fat.
The finding could inform development of novel diabetes and obesity drugs, the scientists said. The study is reported in this month's issue of Cell Metabolism and was selected as the highlighted featured article.
Heat in response to cold
Grb10 is stimulated by cold stress, which causes the body to burn energy. ""We know that if we want to keep our body lean, we have to get rid of extra nutrients in the body, which means burning more energy," said senior author Feng Liu, Ph.D., professor of pharmacology at the UT Health Science Center and director of the Metabolic Syndrome Research Center at Xiangya Second Hospital, Central South University, in Changsha, China.
"Understanding how beigeing is controlled is so very important because if we can improve energy expenditure, we can reduce obesity," Dr. Liu said.
Adipose (fat) tissues, which include white adipose tissue and brown adipose tissue, are important regulators of metabolism. Having too much white adipose tissue and not burning it off through exercise or other energy expenditure is associated with obesity and metabolic diseases such as type 2 diabetes.
"Normally when we eat something, we store it in white fat," said co-author Lily Dong, Ph.D., professor of cellular and structural biology at the UT Health Science Center. "For the extra food we eat, it is better to release it, not store it. So finding a way to turn the white fat into beige and burn the energy that normally we store would have high therapeutic potential for the treatment of obesity and its related diseases. Dr. Liu has identified the pathway to do this."
The mTORC1 pathway is also involved in aging, cardiovascular disease and cancer, so identifying the regulator of this pathway, Grb10, should be very informative for researching other fields, Dr. Liu said.
Drs. Liu and Dong also are members of the Health Science Center's Barshop Institute for Longevity and Aging Studies.
Volume 19, Issue 6, 3 June 2014, Pages 967-980
Grb10 Promotes Lipolysis and Thermogenesis by Phosphorylation-Dependent Feedback Inhibition of mTORC1
Meilian Liu,1,2,7 Juli Bai,1,2 Sijia He,1,2 Ricardo Villarreal,3 Derong Hu,1 Chuntao Zhang,1,4 Xin Yang,3 Huiyun Liang,3 Thomas J. Slaga,1 Yonghao Yu,5 Zhiguang Zhou,2 John Blenis,5 Philipp E. Scherer,6 Lily Q. Dong,3 and Feng Liu1,2
1 Department of Pharmacology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
2 Metabolic Syndrome Research Center and Diabetes Center, Key Laboratory of Diabetes Immunology, Ministry of Education, Second Xiangya Hospital, Central South University, 139 Middle Renmin Road, Changsha, Hunan 410011, China
3 Department of Cellular and Structural Biology, University of Texas Health Science Center at San Antonio, 7703 Floyd Curl Drive, San Antonio, TX 78229, USA
4 The Department of Microbiology, School of Basic Medicine, Xinjiang Medical University, 393 Xinyi Road, Urumqi, Xinjiang 830011, China
5 Department of Cell Biology, Harvard Medical School, 240 Longwood Avenue, Boston, MA 02115, USA
6 Touchstone Diabetes Center, Department of Internal Medicine, and Department of Cell Biology, UT Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-8549, USA
7 Present address: Department of Biochemistry and Molecular Biology, University of New Mexico Health Science Center, 915 Camino de Salud NE, Albuquerque, NM 87131, USA
This work was supported by National Institutes of Health RO1 grant DK100697 and grants from the National Nature Science Foundation of China (81130015) and the National Basic Research Program of China (2014CB910500) to Feng Liu; an American Diabetes Association Junior Faculty Award (1-13-JF-37) and an American Heart Association Beginning in Aid Award (11BGIA7620074) to Meilian Liu; NIH RO1 grants DK69930 to Lily Dong, GM51405 to Juli Bai, and DK55758, DK099110, and P01-DK088761 to Philipp Scherer; an American Cancer Research Center & Foundation grant to Huiyun Liang; and a grant to Thomas Slaga from the Cancer Therapy & Research Center at the UT Health Science Center at San Antonio P30 grant.
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