UH study finds adequate muscle mass acquired early in life may lower risk of obesity and diabetes

HONOLULU - According to a study recently conducted by molecular biologists Dr. Jinzeng Yang and Baoping Zhao in the Department of Human Nutrition, Food and Animal Sciences in the College of Tropical Agriculture and Human Resources (CTAHR) at UH Mānoa, enhanced muscle growth during developmental stages can play a significant role in the prevention of obesity and hyperinsulinemia, a common symptom of pre-diabetes.

Utilizing a unique transgenic mouse model created by Yang and Dr. Robert Wall, a scientist at the USDA-Agricultural Research Service in Beltsville, Maryland, several laboratory experiments using mice with high-fat diets showed significant benefits of enhanced skeletal muscle mass on obesity prevention.

The experiments showed that when mice eat a high-fat diet, they develop typical obesity with accompanying insulin resistance similar to Type II diabetes found in humans. Interestingly, the study found that mice having enhanced muscle mass during early developmental stages were normal with no diabetes present when given a high-fat diet later in the adult age. The amount of fat accumulation in the muscled mice was much less than the non-muscled mice, which showed signs of beginning stages of diabetes, insulin resistance and glucose intolerance, at the end of two-month high-fat feeding trial.

By depressing a key negative regulator of muscle growth, myostatin, through transgenic expression of the myostatin propeptide, Yang and Wall successfully generated transgenic mice with enhanced skeletal muscle growth. "We see genetic effects of the expressed myostatin propeptide in reducing fat deposition," said Yang. "At the same time, we also see physiological effects from the enhanced muscle growth reducing fat accumulation in the adult stage."

The mice also showed increased insulin sensitivity and glucose utilization and changed profiles of metabolic hormones. Yang says that it is the physiological changes resulting from muscle mass accumulated during the growing stages that takes the dietary fat away from adipose tissue. "Therefore, the body is in a healthy, dynamic metabolic state with balanced energy storage and utilization," he added.

A study by the National Center for Health Statistics and the Journal of the American Medical Association found that twenty years ago, 5 percent of 6-19 year olds were overweight; now 15 percent are overweight and the incidence is rising, "Given these results, there is a 90 percent chance an overweight child will become an overweight adult," said Dr. Anne Shovic, associate professor of human nutrition and a registered dietitian at UH Mānoa. "Juvenile obesity definitely results from multi-facet environmental and physiological factors."

Shovic emphasized that we are living in an "obesogenic" environment. "There is an increase in sedentary activities such as watching TV and more urbanization with a plentiful and an easily obtainable food supply," said Shovic. "There is also less physical education programs available in schools. Children spend a quarter to a third of their lives in school, mostly sitting. Honolulu elementary children are lucky to get a half an hour a day of activity." This is in comparison to the recommendation of "60 minutes at most, preferably all days of the week," according to the USDA Dietary Guidelines for Americans 2005, says Shovic.

"This sedentary lifestyle has significantly reduced children's opportunity for physical activity compared with the older generation," said Shovic. "The older generation ate pretty much what they wanted and tended not to be overweight due to their increased workload and activity. The gene pool has not changed but the environment has."

Yang believes that although we cannot genetically program ourselves differently, we can build up a healthy skeletal muscle mass through increased physical activity during the growing and developmental years. Yang adds, "The implication of this mice research model is that the buildup of muscle mass in childhood is extremely important in handling extra food consumption during adulthood. Physiologically, muscle is naturally built up in childhood, up to approximately eighteen years of age. In order to maintain this muscle mass (versus fat), more energy is required. Fat tissue is less metabolically active. Not only is the build up of skeletal muscle in childhood extremely important for normal growth and health, but also for dealing with the obesogenic environment present now and potentially in the future since obesity is so complicated to treat."

In the long-term, Yang and his research team hope to understand how skeletal muscles interact with adipose tissue at the molecular level. With the mice model, they are currently trying to understand the molecular mechanisms of beneficial effects of skeletal muscle buildup on fat reduction. They also plan to study how the signaling pathways of two critical adipocyte hormones, leptin and adiponectin, are changed by the enhanced muscle mass, which may hold a key point in understanding genetic and metabolic basis of obesity and diabetes.

The research work was funded by Hawaiʻi Community Foundation‘s (HCF) Ingeborg V.F. McKee Fund, and the USDA-CSREES-TSTAR funding program.

Two research articles written by Yang and Zhao on these experiments were published in scientific journals "Biochemical and Biophysical Research Communications" Volume 337 (2005): 248-255 and "Molecular Reproduction and Development" Volume 73 (2006): 462-469. To view the articles, visit: http://www.sciencedirect.com/science/journal/0006291X
http://www3.interscience.wiley.com/cgi-bin/jhome/37692

ABOUT CTAHR
The College of Tropical Agriculture and Human Resources (CTAHR), established in 1907 as the College of Agriculture and Mechanical Arts, is the founding college of the University of Hawaiʻi. The college is an integral part of the University of Hawaiʻi at Manoa‘s Carnegie I Research Institution designation and is the Land Grant college of the University of Hawaiʻi system. CTAHR is federally mandated to fulfill the University‘s threefold Land Grant mission of instruction, scientific research, and outreach to address State needs. No other college in the University of Hawaiʻi has such an extensive mandate or interacts so closely with the citizens of the State. The Department of Molecular Biosciences and Bioengineering is one of six departments in the college. For more information, visit www.ctahr.hawaii.edu.