Yan Laboratory
Molecular
Exercise Physiology

Center for Skeletal Muscle Research
Robert M. Berne Cardiovascular Research Center
University of Virginia School of Medicine
409 Lane Road, MR4 - 6041A
Charlottesville, VA 22908
Phone: 434-982-4477
Fax: 434-982-3139
E-mail:
zhen.yan@virginia.edu

Research Topics in Yan Lab

Maternal exercise in prevention of disease in offsping
Type 2 diabetes and heart disease are leading causes of morbidity and mortality with a common origin in gene-environment interactions. Numerous studies have uncovered enduring association of parental conditions to disease susceptibility in the offspring, presenting a dangerous cycle of amplification of disease prevalence and hence the current pandemics. Maternal pro-diabetic conditions cause predisposition of the offspring to the metabolic syndrome, whereas maternal exercise training has profound positive impacts on the offspring; however, the underlying mechanism is unknown. Peroxisome proliferator activated receptor g co-activator-1α (PGC-1α) gene, a master regulator of mitochondrial biogenesis and oxidative metabolis, has been shown to be hypermethylated under the condition of diabetes in skeletal muscle. We hypothesize that maternal exercise prevents hypermethylation of the Pgc-1a gene in offspring skeletal muscle, preventing age-dependent metabolic dysfunction. We are using powerful molecular genetics combined with diet-induced obesity and exercise training to test the hypothesis. The studies will likely provide mechanistic insights into the prevention of parental-offspring transmission of the metabolic syndrome by maternal exercise.

The overall strategy and the central hypothesis that exercise traing during pregnancy modifies the epigenome and lead to reduced susceptibility to insulin resistance in the offspring. Red color depicts insulin resistance.

A pregnant female mouse was running voluntarily on a running wheel (left). Running distance from the pregnant and pseudo-pregnant mice, showing clear differences in running pattern (right).

Publications (Key publications marked ****):
1. Laker RC, Wlodek ME, Connelly JJ, Yan Z. Epigenetic origins of metabolic disease: The impact of the maternal condition to the offspring epigenome and later health consequences. Food Science and Human Wellness . 2013; 2(1):1-11.

2. ****Laker RC, Lillard T, Okutsu M, Zhang M, Hoehn LK, Connelly JJ and Yan Z. Exercise prevents maternal high-fat diet-induced hypermethylation of the Pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes. 2014 Jan 15. [Epub ahead of print] PMID: 24430439. PubMed - in process Link

3. Laker RC, Connelly JJ, Yan Z. Response to comment on Laker et al. Exercise prevents maternal high-fat diet-induced hypermethylation of the pgc-1α gene and age-dependent metabolic dysfunction in the offspring. Diabetes 2014;63:1605-1611. Diabetes. 2014 May;63(5):e6-7. doi: 10.2337/db14-0135. PubMed PMID: 24757208 Link.