Nutrigenomics, Inflammation and Obesity Research Lab (NIOR)
Latha Ramalingam, Ph.D.
We aim to addresses the health benefits of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in early life nutrition by reducing the adverse effects of excessive maternal nutrition. Human and animal studies document that maternal obesity significantly increases both fetal adiposity and the risk of offspring developing obesity later in life. Maternal programming through modulation of dietary components is critical in obesity prevention. n-3 PUFAs like eicosapentaenoic acid (EPA) possess anti-inflammatory and triglyceride-lowering properties that prevent obesity, but their role in maternal supplementation is largely unknown. Hence, we aim to determine if preventing obesity-linked inflammation through EPA supplementation in moms during gestation and early life of mice offspring could reduce adverse effects of maternal obesity.
Role of the Renin Angiotensin System (RAS) in beta cells:
Obesity's prevalence is escalating at an alarming rate in the United States, with more than 79 million Americans suffering from obesity and 30% of these people also suffer from type 2 diabetes and cardiovascular complications indicating that obesity, type 2 diabetes and hypertension are closely related. Studies from Moustaid-Moussa's lab and others have provided evidence linking obesity and insulin resistance to the renin-angiotensin system (RAS), a major regulator of blood pressure and fluid balance .
Angiotensinogen (Agt) is the main precursor in RAS which is catalyzed into angiotensin hormones, with Angiotensin II (Ang II) being the main bioactive hormone in this system . Classically RAS was known to be produced within certain tissues such as the liver (Agt), kidney (Renin), lung (Angiotensin converting enzyme) with additional circulating components (Agt and Ang). However, Agt and other RAS components were unexpectedly found to be also secreted locally in many tissues including adipose and pancreas, where it mostly exerts pro-inflammatory effects [3-5]. Interestingly, this system is clinically important not only because inhibitors of RAS are primarily used to treat hypertension but RAS inhibitors also improve insulin sensitivity in both human and animal studies [6-10]. However, the exact mechanisms mediating these effects of RAS blockade in diabetes are still unclear [3, 11, 12]. Given the dual benefits of RAS blockers in both hypertension, diabetes and potentially obesity as well, it is critical to further dissect their tissue specific mechanisms which may lead to the discovery of novel therapeutic targets for obesity-related type 2 diabetes (T2D).