Deciphering the role of the long noncoding RNA Maternally Expressed 3 (MEG3) in hepatic lipid metabolism

Dr Wong, Chi Ming   (Principal Investigator (PI))

24

2015-06-30

2016-05-03

82600

Deciphering the role of the long noncoding RNA Maternally Expressed 3 (MEG3) in hepatic lipid metabolism

adeno-associated virus vector-mediated gene delivery system, epigenetic modification, lipid metabolism, long noncoding RNA, MEG3

Endocrinology,Diabetes/Metabolism

201411159186

Seed Fund for PI Research – Basic Research

2014

Completed

Obesity is a risk factor for developing numerous comorbidities, such as type 2 diabetes, cardiovascular diseases and certain types of cancers, which imposes huge healthcare burden to our society. The risk factors for obesity are the sedentary lifestyle combined with a high-fat/calorie diet. Exercise and dieting are the basis of treatment for obesity. However, for many people, losing weight by having a healthy diet and doing exercise, requiring huge changes of habits, are not an easy task. Prescription medication is an alternative approach to reduce/control weight by decreasing appetite or absorption of calories. So far, there is no effective and safe drug to cure obesity-related comorbidities. This is mainly due to the limitation in the understanding of obesity-related metabolic dysregulation. Therefore, it is of great importance to study the pathophysiological mechanisms involved in the development of obesity-related metabolic complications and to explore new cost-effective therapies for these diseases. It is well documented that obesity in one or both parents probably influences the risk of obesity in their offspring because of shared genes or environmental factors within families. However, little is known about bout its underlying mechanism. Potential mechanisms such as metabolic/hormonal theories and epigenetic modification and placental effect were proposed (Battista et al., 2011). Interestingly, two recent studies show that the effects of what obese rodents can pass on their obese phenotype to the next generation by non-genetic intergenerational transmission (Dunn and Bale, 2009; Ng et al., 2010). The offspring of obese rodents were more likely to get type 2 diabetes than the control groups by altering their epigenome (Dunn and Bale, 2009). Maternal antioxidant supplementation could prevent adiposity in the offspring of Western diet-fed dams (Ng et al., 2010). In this study, we are going to investigate the role of imprinted gene Maternally Expressed Gene 3 (MEG3) in the transmission of obesity-related diseases from obese parents to offspring. In this project, we are going to Objectives: 1. To explore the expression pattern of MEG3 at different metabolic stages in both dams and their offspring 2. To define the molecular mechanism of how MEG3 regulate lipid metabolism