Start
Oct 05, 2015 - 15:00
End
Oct 05, 2015 - 16:00
Venue
Room # 118 Chem. Engg. Dept.
Event Type
Speaker
Dr Serena D'Souza Project SRF Department of Chemical Engineering Indian Institute of Technology Bombay (IIT B)
Title
Molecular Studies on Metabolic Syndrome
Abstract:Metabolic Syndrome (MetS) is referred to as the clustering of insulin resistance and lipid abnormalities. It is rampant throughout the world across all age groups and its prevalence is found to be dependent on the sex race and ethnicity. Current treatment regimen includes exercise lifestyle changes and medications targeting individual components of the syndrome. The lack of efficacy of this regimen could be due to lack of systematic and holistic studies on MetS per se. The causes for MetS are varied and can be broadly categorised into genetic and environmental. Stress physical inactivity and nutrition excess are key components of the environmental causes. In the current study diet based approach was used to develop a suitable animal model which depicts the real situation seen in humans. MetS was induced in male C57BL/6J mice by feeding specially formulated energy dense High Fat Simple Carbohydrate (HFSC) feed for a period of 5 months. The test mice were hyperphagic; had increased feed efficiency; had significantly higher % increase in body weight waist circumference as compared to control at the end of the study. The test mice were also hyperglycaemic with impaired glucose tolerance and insulin resistance; hypercholesterolemic and hypertriglyceridemic as compared to the control. Further systematic studies on central (brain) and peripheral (plasma and urine) monoamine metabolic pathways revealed that the test mice had lower central(hypothalamic) Serotonergic tone as compared to the control. The test mice were also seen to have significantly lower central (hypothalamic) and peripheral (urine) dopaminergic and significantly higher central(hypothalamic) and peripheral (plasma and urine) Noradrenergic (Norepinephrine) tone as compared to the control crediting Dopamine and Norepinephrine to be used as markers for detection of the syndrome. These results indicate high sympathetic activity and altered Hypothalamic activity. Hyperleptinemia and hyperprolactinemia along with higher levels of cortisol were observed in the test as compared to the control indicating perturbation of the Hypothalamic-Pituitary-Adrenal (HPA) axis. The observed altered carbohydrate and lipid metabolism monoamine metabolic pathway and HPA axis in the test pointed towards a possible role of a nuclear receptor Peroxisome Proliferator Activated Receptor (PPAR) subtypes γ and β/δ. In an attempt to ameliorate the syndrome novel antagonists against PPAR γ and agonists against PPAR β/δ were identified using an in silico (docking) approach.Bio-data: Dr Serena D'Souza is a project senior research fellow under Prof. Santosh Noronha of Department of Chemical Engineering IIT Bombay.