Session Speaker

n-3 Fatty Acids Prevents Left Ventricular Hypertrophy and Bone Loss Caused by Rosiglitazone Therapy in Diabetic Aging Mice
Gabriel Fernandes
USA

Both obesity and the incidence of type 2 diabetes are rising worldwide. There is a common usage of of PPAR_γ agonist Rosiglitazone (RSG) to control diabetes. Although, it is known that diabetes can be controlled by RSG therapy, there is also a significant risk in developing myocardial infraction or heart failure, as well as bone loss, in RSG treated diabetic patients. We therefore conducted an animal study in 13 mo old mice fed a diet with 10% corn oil alone, 10% CO with RSG (140mg/kg of diet). 5%corn oil +5% fish oil +RSG. We measured left ventricle (LV) function by echocardiography and bone mineral density (BMD) using DXA after 4 months on a dietary intervention. RSG treatment alone developed a significant rise in LV hypertrophy and decreased fractional shortening (FS). In contrast, LV hypertrophy was prevented in mice fed with RSG+FO. Importantly, the high fat diet induced hyperglycemia was controlled by RSG, as well as in RSG+FO fed mice. Further, dietary supplementation of FO with RSG had an anti-inflammatory effect in the LV, as evidenced by a decreased level of pro-inflammatory cytokines (IL-6, TNF-α) and increased IL-10 and antioxidant capacity in the LV tissue. Additionally, we also examined bone morphogenic protein 2 (BMP 2) induced osteogenesis and adipogenesis in mesenchymal fibroblastic C3H10T1/2 cell line, treated with RSG and with n-3 fatty acids which showed a reduced adipogenesis, particularly by decosahexanoic acid (DHA), which is one of the fatty acids component of fish oil. Further, FO with RSG fed mice prevented the loss of BMD, by inhibiting bone resorption, primarily by decreasing pro-inflammatory cytokines (IL-6 and TNF-α) and reducing cathepsin K expression in bone marrow cells, when compared to RSG alone fed mice. In conclusion, these new findings revealed that dietary supplementation of FO with RSG may improve FS, by attenuating cardiac LV remodeling as well as preventing also the loss of BMD. This present study suggests future clinical trials with RSG therapy with and without the usage of prescription approved n-3 fatty acids supplements in diabetic patients should be investigated.