Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPAR¦Ã, PPAR¦Á and e-NOS

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• 作者：Ashok Kumar Sharma ; Saurabh Bharti ; Jagriti Bhatia ; Saroj Nepal ; Salma Malik ; Ruma Ray ; Santosh Kumari ; Dharamvir Singh Arya
• 关键词：Sesamol ; Cardiometabolic syndrome ; PPAR¦Ã ; Insulin resistance ; SERBP-1c ; e-NOS
• 刊名：Journal of Nutritional Biochemistry
• 出版年：2012
• 出版时间：November, 2012
• 年：2012
• 卷：23
• 期：11
• 页码：1482-1489
• 全文大小：1806 K

文摘

Increased oxidative stress and inflammation in obesity are the central and causal components in the pathogenesis and progression of cardiometabolic syndrome (CMetS). The aim of the study was to determine the potential role of sesamol (a natural powerful antioxidant and anti-inflammatory phenol derivative of sesame oil) in chronic high-cholesterol/high-fat diet (HFD)-induced CMetS in rats and to explore the molecular mechanism driving this activity. Rats were fed with HFD (55 % calorie from fat and 2 % cholesterol) for 60 days to induce obesity, dyslipidemia, insulin resistance (IR), hepatic steatosis and hypertension. On the 30th day, rats with total cholesterol >150 mg/dl were considered hypercholesterolemic and administered sesamol 2, 4 and 8 mg/kg per day for the next 30 days. Sesamol treatment decreased IR, hyperinsulinemia, hyperglycemia, dyslipidemia, TNF-¦Á, IL-6, leptin, resistin, highly sensitive C-reactive protein (hs-CRP), hepatic transaminases and alkaline phosphatase, along with normalization of adiponectin, nitric oxide and arterial pressures in a dose-dependent fashion. Increased TBARS, nitrotyrosine and decreased antioxidant enzyme activities were also amended in HFD rats. Similarly, sesamol normalized hepatic steatosis and ultrastructural pathological alteration in hepatocytes, although the effect was more pronounced at 8 mg/kg. Furthermore, hepatic PPAR¦Ã, PPAR¦Á and e-NOS protein expressions were increased, whereas LXR¦Á, SERBP-1c, P-JNK and NF-¦ÊB expression were decreased by sesamol treatment. These results suggest that sesamol attenuates oxidative stress, inflammation, IR, hepatic steatosis and hypertension in HFD-fed rats via modulating PPAR¦Ã, NF-¦ÊB, P-JNK, PPAR¦Á, LXR¦Á, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS.