Obesity - Currently Funded
Dr. Jean-Luc Ardilouze (Operating Grant funded 2011-2014)
Universite de Sherbrooke (Sherbrooke, QC)
Title: Improvement of insulin pharmacokinetics in obese subjects with type 2 diabetes.
Absorption of insulin into the body depends mainly on adipose tissue blood flow (ATBF). ATBF is 50%-70% lower in obese people with type 2 diabetes than in normal-weight, healthy people. Dr. Jean-Luc Ardilouze is examining whether a combined injection of insulin and a pharmacological agent will modulate ATBF and, in turn, improves how insulin acts and is absorbed in obese people with type 2 diabetes. This research could affect how insulin is formulated in the future and may enable better management of type 2 diabetes in obese people.
Dr. Danna M. Breen (Postdoctoral Fellowship Award funded 2012-2015)
University Health Network (Toronto, ON)
Supervisor: Dr. Tony K.T. Lam
Title: A novel site of leptin action that regulates glucose homeostasis.
In diabetes and obesity, the liver begins to overproduce glucose. The hormone leptin works in the brain to regulate liver glucose production, but leptin is also released by the stomach and leptin receptors are found in a part of the small intestine called the jejunum. Gastric duodenal bypass surgery (which involves attaching a tiny part of the stomach into the small intestine and bypassing most of the stomach and the part of the small intestine called the duodenum) lowers blood glucose in diabetes and obesity. Dr. Danna Breen will evaluate if the hormone leptin works in the jejunum to lower glucose production and if this is enhanced after gastric duodenal bypass surgery to further lower blood glucose. Dr. Breen hopes to identify new targets for lowering blood glucose in diabetes.
Dr. Hsiao-Huei Chen (Operating Grant funded 2011-2014)
Ottawa Hospital Research Institute (Ottawa, ON)
Title: Neural control of metabolism
Leptin, a hormone produced from fat cells, acts on a specific area of the brain to reduce feeding, increase fat metabolism, and improve insulin sensitivity. Although most obese people have higher levels of leptin in their body, its effects are reduced, a condition called central leptin resistance. Dr. Hsiao-Huei Chen is investigating whether this resistance is due, in part, to the loss of a specific protein, called LMO4, in the brain. This research could help find a way to restore leptin sensitivity which is a key challenge in treating obesity and type 2 diabetes.
Ms. Maria F. A. Fernandes (Doctoral Student Research Award funded 2010-2013)
University of Montreal (Montréal, QC)
Supervisor: Dr. Stephanie E. Fulton
Title: Role of STAT3 in the actions of leptin in the ventral tegmental area to reduce food intake and modulate dopamine tome
The hormone leptin acts in the brain to influence hunger and eating behaviours by turning on a molecule called STAT3. Ms. Maria Fernandes will remove STAT3 to determine if eating behaviours change as a result. This study will increase knowledge about the mechanisms behind feeding and obesity, and could provide potential therapeutic targets for the treatment of obesity and type 2 diabetes.
Dr. Marie-Soleil Gauthier (Postdoctoral Fellowship Award funded 2010-2013)
CHUM-Research Centre, Hotel-Dieu Campus (Montréal, QC)
Supervisors: Dr. Rémi Rabasa-Lhoret and Dr. Marc Prentki
Title: Role of AMP-activated protein kinase in adipose tissue inflammation, oxidative stress and insulin resistance
Inflammation in fat is known to be a major cause of insulin resistance, a risk factor for developing type 2 diabetes. Dr. Marie-Soliel Gauthier is investigating how and why inflammation happens by studying a molecule called AMPK , a fuel-sensing enzyme. Dr. Gauthier hopes that a better understanding of mechanisms that lead to adipose tissue inflammation and insulin resistance should help in the development of therapeutics against obesity-associated diabetes.
Dr. Sanjoy Ghosh (Operating Grant funded 2012-2015)
University of British Columbia-Okanagan (Kelowna, BC)
Title: Cardiac oxidative stress in diet induced obesity: Role of polyunsaturated fatty acids
In recent years, Canadian diets have included more of the type of fat called omega‐6 polyunsaturated fatty acids (omega‐6), which are mainly found in vegetable oils. Omega‐6 is commonly thought to be a "healthy" fat, but recent studies have shown that too much omega‐6 may damage heart muscle, cause inflammation, and may even cause cell death. Dr. Sanjoy Ghosh believes that, during obesity, too much omega‐6 causes the energy‐producing "engines" of the cells (called mitochondria) to make damaging molecules called free radicals, which can cause heart cell damage. Dr. Ghosh and his team will investigate specifically how omega‐6 causes damage in the mitochondria. Dr. Ghosh also aims to determine if this damage can be reduced by supplementation with beneficial fish oils. This research will identify the process by which common dietary fats are increasing obesity and diabetes‐related heart disease in Canada.
Dr. Sanjoy Ghosh (Scholar Award funded 2010-2015)
University of British Columbia-Okanagan (Kelowna, BC)
Title: Cardiolipotoxicity of omega-6 polyunsaturated fatty acids in diabetes
In recent years, Canadian diets have included more of the type of fat called omega‐6 polyunsaturated fatty acids (omega-6), which are mainly found in vegetable oils. Omega-6 is commonly thought to be a "healthy" fat, but recent studies have shown that too much omega-6 may damage heart muscle, cause inflammation, and may even cause cell death. Dr. Sanjoy Ghosh believes that, during obesity, too much omega-6 causes the energy-producing "engines" of the cells (called mitochondria) to make damaging molecules called free radicals, which can cause heart cell damage. Dr. Ghosh and his team will investigate specifically how omega-6 causes damage in the mitochondria. Dr. Ghosh also aims to determine if this damage can be reduced by supplementation with beneficial fish oils. This research will identify the process by which common dietary fats are increasing obesity and diabetes‐-elated heart disease in Canada.
Dr. Amira Klip (Operating Grant funded 2012-2015)
The Hospital for Sick Children (Toronto, ON)
Title: Endothelial and transendothelial events underlying immune cell infiltration of metabolic tissues in pre-diabetes
Obesity and diets rich in saturated fats are major contributing factors to insulin resistance, which in turn is a risk factor for type 2 diabetes. Obesity is accompanied by low-level inflammation in fat tissue, which is caused by white blood cells (immune system cells) moving out of the blood stream and into the tissues. Dr. Amira Klip and her team recently discovered that muscle tissue is also inflamed in obesity, and that too many saturated fats in the diet make muscle cells attract white blood cells. During her current research, Dr. Klip, co-applicant Dr. Lee and their team are investigating why white blood cells are attracted to muscle tissues during obesity, if saturated fats make white blood cells leave the blood vessels, and if it is possible to prevent insulin resistance in muscles by keeping the white blood cells out of the muscle tissues. Dr. Klip hopes to better understand how inflammation happens and how it contributes to insulin resistance. She hopes to block white blood cells from entering muscles to prevent insulin resistance and type 2 diabetes from developing.
Dr. Julie L. Lavoie (Operating Grant funded 2011-2014)
Université de Montréal (Montréal, QC)
Title: Implication of the prorenin/renin receptor in the development of obesity and type 2 diabetes
Dr. Julie L. Lavoie is investigating a promising antiobesity drug in mice. Her previous studies have shown that mice which develop obesity by being placed on a typical North American diet (rich in sugar and fat) gained less weight while receiving this drug. In her current study, Dr. Lavoie is trying to determine if the drug could also lower other health risks, such as diabetes. A drug that could treat obesity and also reduce many of its complications, such as type 2 diabetes diabetes, would be of extreme usefulness clinically.
Dr. Gary D. Lopaschuk (Operating Grant funded 2012-2015)
University of Alberta (Edmonton, AB)
Title: Hypothalamic malonyl-CoA control of obesity.
Obesity occurs when food (energy) intake is greater than body energy expenditure. Obesity is a major risk factor for the development of type 2 diabetes. Dr. Gary Lopaschuk is focusing on a molecule called malonyl‐CoA, which regulates body fat metabolism. This molecule also plays an important role in how eating and expenditure are regulated in the brain. Dr. Lopaschuk is studying how malonyl‐CoA works on a molecular level, and how the process of food and energy control works in response to, and in the absence of, various hormones. Through the course of these studies, Dr. Lopaschuk aims to better understand how eating and body energy use are controlled. He believes this knowledge will be useful in developing new therapies that can treat obesity and, therefore, decrease the incidence of diabetes.
Mr. Jeevan Nagendran (Doctoral Student Research Award funded 2012-2013)
University of Alberta (Edmonton, AB)
Supervisors: Dr. Jason R.B. Dyck and Dr. Finlay A. McAlister
Title: The Involvement of CD36 in the Regulation of Myocardial Metabolism and Function in Insulin Resistance and Obesity
Obesity is a risk factor for cardiovascular (heart and blood vessel) disease and type 2 diabetes. When heart cells accumulate extra fat, they begin to work poorly which can lead to heart disease. Using obese mice, Dr. Jeevan Nagendran plans to examine the process that causes fat to accumulate in the heart in obesity, and further to examine if blocking this fat accumulation process helps or harms heart function. These studies will help identify new ways to treat or prevent heart disease in people with obesity and type 2 diabetes.
Dr. Jonathan D. Schertzer (Operating Grant funded 2012-2015; Scholar Award funded 2012-2017)
McMaster University (Hamilton, ON)
Title (Operating Grant): NOD2 immunity protects against obesity-induced inflammation and insulin resistance
Title (Scholar Award): Title: NOD proteins link immunity with obesity, insulin resistance and diabetes.
Insulin resistance is a major risk factor for type 2 diabetes. Obesity is associated with low-level inflammation in the body, and is a major contributing factor to insulin resistance. Dr. Jonathan Schertzer and his team have discovered an immune system protein (called NOD2) that is important in preventing excessive obesity and insulin resistance. If NOD2 is missing, there is a series of changes that starts with the bacteria in the gut, moving to the liver and fat, and resulting in whole-body insulin resistance. Dr. Schertzer aims to figure out how NOD2 helps the immune system protect against insulin resistance. Dr. Schertzer believes that missing NOD2 causes in inflammation in the fat surrounding the gut and liver, and that probiotics could activate NOD2 to reduce inflammation and insulin resistance. This work could allow doctors to better monitor specific patients with insulin resistance, and could even allow for the development of treatments to prevent type 2 diabetes using specific probiotics in the diet.
Dr. Eva Tudurí (Postdoctoral Fellowship Award funded 2011-2014)
University of British Columbia (Vancouver, BC)
Supervisor: Dr. Timothy J. Kieffer
Title: Leptin resistance in the endocrine pancreas
The hormone leptin is produced by fat cells and its circulating blood levels correlate to body fat content. Leptin resistance in the brain has been reported in obese individuals. The lack of leptin signalling in cells that secrete insulin results in similar features to those in people with diabetes, providing a potential link between leptin resistance in insulin-secreting cells and obesity-related diabetes. Also, absence of leptin signalling in cells that secrete glucagon may contribute to the high blood levels of glucagon observed in people with diabetes. Dr. Tudurí is trying to better understand the consequences caused by the lack of leptin signalling in the endocrine pancreas and the cellular mechanisms that underlie these consequences. This research could lead to the development of new therapies for people with type 2 diabetes.
Dr. Minna Woo (Operating Grant funded 2011-2014)
St Michael's Hospital (Toronto, ON)
Title: Molecular Dissection of Inflammation and Insulin Resistance in Metabolic Syndrome
The obesity epidemic from excess caloric intake and sedentary lifestyle has led to an alarming increase in the incidence of type 2 diabetes. Excess fat is most safely stored in fat tissue under the skin, resulting in a "pear shaped body", as opposed to unhealthy space – such as in the abdomen, resulting in an "apple shaped body". Fats stored in this latter space are considered to be toxic. And although the liver has been found to be another site of storage for toxic fat, some data show that the liver may also be a safe place to store fat. Dr. Minna Woo is investigating the factors within liver cells that make the body either metabolically healthy or unhealthy, which can determine diabetes outcome. This research will enable us to better understand the relationship between fatty liver and type 2 diabetes, which could lead to new strategies for disease treatment.
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