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Hyperlipidemia‐induced hepatic and small intestine ER stress and decreased paraoxonase 1 expression and activity is associated with HDL dysfunction in Syrian hamsters
Author(s) -
Stancu Camelia S.,
Carnuta Mihaela G.,
Sanda Gabriela M.,
Toma Laura,
Deleanu Mariana,
Niculescu Loredan S.,
Sasson Shlomo,
Simionescu Maya,
Sima Anca V.
Publication year - 2015
Publication title -
molecular nutrition and food research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.495
H-Index - 131
eISSN - 1613-4133
pISSN - 1613-4125
DOI - 10.1002/mnfr.201500422
Subject(s) - medicine , endocrinology , pon1 , hyperlipidemia , paraoxonase , oxidative stress , small intestine , steatosis , hamster , liver x receptor , triglyceride , receptor , cholesterol , biology , chemistry , nuclear receptor , biochemistry , diabetes mellitus , genotype , transcription factor , gene
Scope We aimed at investigating the mechanisms linking hyperlipidemia (HL) with dysfunctional HDL and its main antioxidant enzyme, paraoxonase1 (PON1). PON1 expression and activity was determined in the small intestine, liver, and sera of normal and HL hamsters and associated with the ER stress (ERS) and the development of aortic valve lesions. Methods and results Male Golden Syrian hamsters were fed standard chow (N) or standard diet with 3% cholesterol and 15% butter for 16 weeks. All hamsters on fat diet developed HL, 50% also hyperglycemia (HLHG) and a fourfold increased homeostasis model assessment of insuline resistance. PON1 expression was reduced in the small intestine and liver (N > HL > HLHG) along with the increased extent of ERS, oxidized lipids, and decreased expression of liver X receptors beta (LXRβ) in the small intestine, peroxisome proliferator‐activated receptor‐γ (PPARγ) in the liver, and of the glucose transporter 4 in the myocardium. Serum PON1 levels decreased along with the increase of oxidized LDL and lesion areas of the aortic valves (N > HL > HLHG). Conclusion The fat diet activates the ERS and oxidative stress, decreases LXRβ, PPARγ, and PON1 in the small intestine, liver, and sera of all HL animals, in parallel with the appearance of atherosclerotic lesions in the aortic valves.