title: An immunomodulating fatty acid analogue targeting mitochondria exerts anti-atherosclerotic effect beyond plasma cholesterol-lowering activity in apoe(-/-) mice.
abstract: Tetradecylthioacetic acid (TTA) is a hypolipidemic antioxidant with immunomodulating properties involving activation of peroxisome proliferator-activated receptors (PPARs) and proliferation of mitochondria. This study aimed to penetrate the effect of TTA on the development of atherosclerotic lesions in apolipoprotein (apo)-E(-/-) mice fed a high-fat diet containing 0.3% TTA for 12 weeks. These mice displayed a significantly less atherosclerotic development vs control. Plasma cholesterol was increased by TTA administration and triacylglycerol (TAG) levels in plasma and liver were decreased by TTA supplementation, the latter, probably due to increased mitochondrial fatty acid oxidation and reduced lipogenesis. TTA administration also changed the fatty acid composition in the heart, and the amount of arachidonic acid (ARA) and eicosapentaenoic acid (EPA) was reduced and increased, respectively. The heart mRNA expression of inducible nitric oxidase (NOS)-2 was decreased in TTA-treated mice, whereas the mRNA level of catalase was increased. Finally, reduced plasma levels of inflammatory mediators as IL-1α, IL-6, IL-17, TNF-α and IFN-γ were detected in TTA-treated mice. These data show that TTA reduces atherosclerosis in apoE(-/-) mice and modulates risk factors related to atherosclerotic disorders. TTA probably acts at both systemic and vascular levels in a manner independent of changes in plasma cholesterol, and triggers TAG catabolism through improved mitochondrial function.
authors: Department of Clinical Science, University of Bergen, Bergen, Norway.
authors: Rita
authors: R
authors: Vik
authors: Marco
authors: M
authors: Busnelli
authors: Cinzia
authors: C
authors: Parolini
authors: Bodil
authors: B
authors: Bjørndal
authors: Sverre
authors: S
authors: Holm
authors: Pavol
authors: P
authors: Bohov
authors: Bente
authors: B
authors: Halvorsen
authors: Trond
authors: T
authors: Brattelid
authors: Stefano
authors: S
authors: Manzini
authors: Giulia S
authors: GS
authors: Ganzetti
authors: Federica
authors: F
authors: Dellera
authors: Ottar K
authors: OK
authors: Nygård
authors: Pål
authors: P
authors: Aukrust
authors: Cesare R
authors: CR
authors: Sirtori
authors: Giulia
authors: G
authors: Chiesa
authors: Rolf K
authors: RK
authors: Berge
mesh_terms: D000818:Animals; D001057:Apolipoproteins E / Q000172:deficiency* / Q000378:metabolism; D050197:Atherosclerosis / Q000097:blood* / Q000188:drug therapy* / Q000473:pathology; D001835:Body Weight / Q000187:drug effects; D002784:Cholesterol / Q000097:blood*; D059305:Diet, High-Fat; D019587:Dietary Supplements; D005227:Fatty Acids / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects; D007155:Immunologic Factors / Q000494:pharmacology / Q000627:therapeutic use*; D007249:Inflammation / Q000097:blood / Q000235:genetics / Q000473:pathology; D008099:Liver / Q000187:drug effects / Q000201:enzymology / Q000473:pathology; D051379:Mice; D008928:Mitochondria / Q000187:drug effects / Q000378:metabolism*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D018384:Oxidative Stress / Q000187:drug effects / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013440:Sulfides / Q000494:pharmacology / Q000627:therapeutic use*
chemical_list: D001057:Apolipoproteins E; D005227:Fatty Acids; D007155:Immunologic Factors; D012333:RNA, Messenger; D013440:Sulfides; C062078:1-(carboxymethylthio)tetradecane; D002784:Cholesterol