A research group at Maine Medical Center (MMC) has received $1.3 million from the National Institutes of Health (NIH) to study how the activity of a certain gene — called mesoderm specific transcript, or MEST — affects obesity and blood sugar.
Researchers hope their studies will shed light on how this gene is involved in body fat accumulation. In the future, this knowledge could lead to new therapeutic strategies for the treatment of obesity and type 2 diabetes.
The grant was awarded to Robert Koza, PhD, a faculty scientist at MMC Research Institute (MMCRI). Koza and his team have been studying the biological mechanisms and genes underlying environmentally triggered changes — like those driven by a high-fat diet — in the development of diseases such as obesity and diabetes.
The focus of their investigations is a particular type of genetic change termed epigenetic changes. These consist of DNA modifications that do not change the DNA sequence but affect gene activity — meaning the way in which genes are expressed, or “turned on.”
Environmental factors, like aging and diet, can induce epigenetic changes in certain genes that alter their activity. Many of these changes have consequences for the growth, metabolism, or defense mechanisms of cells and tissues in the body.
Previous studies from Koza and his group indicate that mice are less likely to become obese on a high-fat diet when MEST is not expressed or expressed at low levels.
Scientists now seek to understand how MEST expression changes the amount of fat mass in the body, and what are the precise epigenetic changes regulating its expression.
In one study, mice fed a high-fat diet and genetically engineered to lack MEST activity in all tissues, or only in the adipose (fat) tissue, accumulated less fat and showed improved glucose (sugar) tolerance. Impaired glucose tolerance means that blood glucose is raised beyond normal levels, increasing the risk of developing diabetes and cardiovascular disease.
“Identifying the molecular pathways by which MEST facilitates the expansion of fat mass and regulates blood glucose could be the first step towards a new way to help treat obesity,” Koza said in a press release.
“Years from now, these studies may also define new early interventions doctors could take to help patients prevent the development of obesity and type 2 diabetes,” he added.
Metabolic diseases like diabetes and obesity are a focus of research at MMCRI because of their prevalence in Maine. The Centers for Disease Control and Prevention in 2016 listed Maine as having an obesity rate of 30% and a diabetes rate of 8.5%, the highest in New England.