title: Sesamol alleviates diet-induced cardiometabolic syndrome in rats via up-regulating PPARγ, PPARα and e-NOS.
abstract: 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-α, 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 PPARγ, PPARα and e-NOS protein expressions were increased, whereas LXRα, SERBP-1c, P-JNK and NF-κB 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 PPARγ, NF-κB, P-JNK, PPARα, LXRα, SREBP-1c and e-NOS protein expressions, thereby preventing CMetS. Thus, the present study demonstrates the therapeutic potential of sesamol in alleviating CMetS.
authors.affiliation: Department of Pharmacology, Cardiovascular Research Laboratory, All India Institute of Medical Sciences, New Delhi-110029, India.
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Sharma
authors.forename: Saurabh
authors.initials: S
authors.lastname: Bharti
authors.forename: Jagriti
authors.initials: J
authors.lastname: Bhatia
authors.forename: Saroj
authors.initials: S
authors.lastname: Nepal
authors.forename: Salma
authors.initials: S
authors.lastname: Malik
authors.forename: Ruma
authors.initials: R
authors.lastname: Ray
authors.forename: Santosh
authors.initials: S
authors.lastname: Kumari
authors.forename: Dharamvir Singh
authors.initials: DS
authors.lastname: Arya
mesh_terms: D000818:Animals; D000975:Antioxidants / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology*; D001835:Body Weight / Q000187:drug effects; D002318:Cardiovascular Diseases / Q000188:drug therapy* / Q000209:etiology / Q000378:metabolism*; D002784:Cholesterol / Q000097:blood; D059305:Diet, High-Fat / Q000009:adverse effects; D004305:Dose-Response Relationship, Drug; D050171:Dyslipidemias / Q000188:drug therapy / Q000209:etiology; D005234:Fatty Liver / Q000188:drug therapy; D022781:Hepatocytes / Q000187:drug effects / Q000648:ultrastructure; D006943:Hyperglycemia / Q000188:drug therapy / Q000378:metabolism; D006973:Hypertension / Q000150:complications / Q000209:etiology; D007333:Insulin Resistance; D008297:Male; D009569:Nitric Oxide / Q000097:blood; D052250:Nitric Oxide Synthase Type III / Q000378:metabolism*; D009765:Obesity / Q000150:complications / Q000209:etiology; D047493:PPAR alpha / Q000378:metabolism*; D047495:PPAR gamma / Q000378:metabolism*; D010636:Phenols / Q000494:pharmacology*; D051381:Rats; D017208:Rats, Wistar; D013482:Superoxide Dismutase / Q000378:metabolism; D017392:Thiobarbituric Acid Reactive Substances / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000975:Antioxidants; D052117:Benzodioxoles; D047493:PPAR alpha; D047495:PPAR gamma; D010636:Phenols; D017392:Thiobarbituric Acid Reactive Substances; D009569:Nitric Oxide; C025583:sesamol; D002784:Cholesterol; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D013482:Superoxide Dismutase