Most Significant Contributions
In the Western world, changing environmental factors like diet and sedentary lifestyle have been pivotal in the rapid development of diabetes and obesity, and their associated cardiovascular diseases in recent years. Dr. Ghosh’s research interest lies in identifying and preventing the cardiovascular impact of such recent environmental changes in diabetes and obesity. Some highlights so far:
1. Mitochondrial glutathione (GSH) loss initiates cardiac cell death in diabetes. Early during his graduate studies, Dr. Ghosh identified for the first time that in diabetic rats, increased cardiac oxidative stress and cell death is primarily a result of increased generation of free radicals from the mitochondria as a direct consequence of the loss of mitochondrial antioxidant GSH (Ghosh S, et al, Am. J. Physiol., 2005). He also demonstrated that this decrease in GSH is due to efflux of GSH from cardiac cells by a novel transporter known as multidrug resistance protein 1, commonly found in the gut and liver (Ghosh S, et al, Can. J. Physiol. Pharmacol., 2004).
2. Impact of high fat diets with omega-6 polyunsaturated fatty acids (PUFA) on heart disease In the Western world, “heart-friendly” refined vegetable oils like sunflower oil, safflower oil and corn oils, rich in omega-6 but low in omega-3 PUFA have also increased in recent years. Dr. Ghosh showed that cardiac damage and the decreased cardiac function in diabetes are worsened by omega-6 PUFA (Ghosh S, et al, Nutrition 2004; Ghosh S, et al, Am. J. Physiol., 2004), thus providing an explanation to the rise in diabetic heart disease in the Western countries like Canada in recent years. After the ground-breaking results, Dr. Ghosh was awarded the John M. Kinney Award for Nutritional Science in the ‘Best paper in Nutrition and Metabolism’ category by the journal ‘Nutrition’ in association with Nestle and the European Society of Parenteral and Enteral Nutrition in Brussels, Belgium. As diabetes in rats fed a omega-6 PUFA leads to mitochondrial damage and cardiac dysfunction very rapidly, he also demonstrated that under obesity without diabetes, such diet can ‘prime’ the heart for damage. (Ghosh S, et al, Free Radical Biology and Medicine, 2006). This suggested for the first time that high fat diet with omega-6 PUFA damages the heart even in the absence of any disease. In all the above studies, high fat diets were used. High fat feeding per se (i.e. caloric intake) can be an independent variable causing inflammation and oxidative stress. As the next logical step, Dr. Ghosh demonstrated that even under normal caloric intakes, omega-6 PUFA can cause cardiac oxidative stress and inflammatory signaling (Ghosh S, et al, Am. J. Physiol., 2007) in early adulthood
3. Moderate exercise can improve diabetic cardiovascular function without obvious metabolic changes The classical explanation of the benefit of exercise is via improvement of metabolic parameters in obesity/diabetes. However, with my previous observations of oxidative stress as the prime modulator of cardiovascular diseases, and with the help of independent collaborative efforts, that I initiated, we recently established the exercise in diabetes need not be intensive to alter metabolic parameters. Even moderate exercise can benefit diabetic complications in multiple organ systems, predominantly by upregulation of endogenous antioxidants and prevention of cell death in the aorta (Afsari FM and Ghosh S, et al, Diabetologia, 2008), heart (Afsari FM and Ghosh S, et al, Am. J. Physiol., 2008) and kidney (Ghosh S, et al, Am. J. Physiol., 2009) in db/db mice model of obesity/type 2 diabetes.