Advertisement

Dietary supplementation with long-chain monounsaturated fatty acid isomers decreases atherosclerosis and alters lipoprotein proteomes in LDLr−/− mice

      Highlights

      • Some fish oils are enriched in long-chain monounsaturated fatty acids (LCMUFA).
      • LCMUFA isomers (C20:1, C22:1) fractions inhibited atherosclerosis in LDLR-KO mice.
      • There were no major differences in plasma lipoproteins or hepatic lipid content.
      • Proteomic analysis revealed lipoprotein composition changes by LCMUFA isomers.
      • Several lipoprotein proteome changes significantly correlated with atherosclerotic reduction.

      Abstract

      Background and aims

      Concentrated fish oils, containing a mixture of long-chain monounsaturated fatty acids (LCMUFA) with aliphatic chains longer than 18 C atoms (i.e., C20:1 and C22:1), have been shown to attenuate atherosclerosis development in mouse models. It is not clear, however, how individual LCMUFA isomers may act on atherosclerosis.

      Methods

      In the present study, we used saury fish oil-derived concentrates enriched in either C20:1 or C22:1 isomer fractions to investigate their individual effect on atherosclerosis and lipoprotein metabolism. LDLR-deficient (LDLr−/−) mice were fed a Western diet supplemented with 5% (w/w) of either C20:1 or C22:1 concentrate for 12 wk.

      Results

      Compared to the control Western diet with no supplement, both LCMUFA isomers increased hepatic levels of LCMUFA by 2∼3-fold (p < 0.05), and decreased atherosclerotic lesion areas by more than 40% (p < 0.05), although there were no major differences in plasma lipoproteins or hepatic lipid content. Both LCMUFA isomers significantly decreased plasma CRP levels, improved Abca1-dependent cholesterol efflux capacity of apoB-depleted plasma, and enhanced Ppar transcriptional activities in HepG2 cells. LC-MS/MS proteomic analysis of lipoproteins (HDL, LDL and VLDL) revealed that both LCMUFA isomer diets resulted in similar potentially beneficial alterations in proteins involved in complement activation, blood coagulation, and lipid metabolism. Several lipoprotein proteome changes were significantly correlated with atherosclerotic plaque reduction.

      Conclusions

      Dietary supplementation with the LCMUFA isomers C20:1 or C22:1 was equally effective in reducing atherosclerosis in LDLr−/−mice and this may partly occur through activation of the Ppar signaling pathways and favorable alterations in the proteome of lipoproteins.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to Atherosclerosis
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Hooper L.
        • Summerbell C.D.
        • Thompson R.
        • Sills D.
        • Roberts F.G.
        • et al.
        Reduced or modified dietary fat for preventing cardiovascular disease.
        Cochrane Database Syst. Rev. 2011; 7: CD002137
        • Schwingshackl L.
        • Hoffmann G.
        Monounsaturated fatty acids, olive oil and health status: a systematic review and meta-analysis of cohort studies.
        Lipids Health Dis. 2014; 13: 154
        • Yang Z.H.
        • Emma-Okon B.
        • Remaley A.T.
        Dietary marine-derived long-chain monounsaturated fatty acids and cardiovascular disease risk: a mini review.
        Lipids Health Dis. 2016; 15: 201
        • Yang Z.H.
        • Bando M.
        • Sakurai T.
        • Chen Y.
        • Emma-Okon B.
        • et al.
        Long-chain monounsaturated fatty acid-rich fish oil attenuates the development of atherosclerosis in mouse models.
        Mol. Nutr. Food Res. 2016; 60: 2208-2218
        • Matsumoto C.
        • Matthan N.R.
        • Lichtenstein A.H.
        • Gaziano J.M.
        • Djoussé L.
        Red blood cell MUFAs and risk of coronary artery disease in the Physicians' Health Study.
        Am. J. Clin. Nutr. 2013; 98: 749-754
        • Kim D.S.
        • Maden S.K.
        • Burt A.A.
        • Ranchalis J.E.
        • Furlong C.E.
        • et al.
        Dietary fatty acid intake is associated with paraoxonase 1 activity in a cohort-based analysis of 1,548 subjects.
        Lipids Health Dis. 2013; 12: 183
        • Gordon S.M.
        • Remaley A.T.
        High density lipoproteins are modulators of protease activity: implications in inflammation, complement activation, and atherothrombosis.
        Atherosclerosis. 2017; 259: 104-113
        • Burillo E.
        • Martín-Fuentes P.
        • Mateo-Gallego R.
        • Baila-Rueda L.
        • Cenarro A.
        • et al.
        Omega-3 fatty acids and HDL. How do they work in the prevention of cardiovascular disease?.
        Curr. Vasc. Pharmacol. 2012; 10: 432-441
        • Wang S.
        • Awad K.S.
        • Elinoff J.M.
        • Dougherty E.J.
        • Ferreyra G.A.
        • et al.
        G protein-coupled receptor 40 (GPR40) and peroxisome proliferator-activated receptor γ (PPARγ): an integrated two-receptor signaling pathway.
        J. Biol. Chem. 2015; 290: 19544-19557
        • Gordon S.M.
        • McKenzie B.
        • Kemeh G.
        • Sampson M.
        • Perl S.
        • et al.
        Rosuvastatin alters the proteome of high density lipoproteins: generation of alpha-1-antitrypsin enriched particles with anti-inflammatory properties.
        Mol. Cell Proteom. 2015; 14: 3247-3257
        • Gordon S.M.
        • Deng J.
        • Lu L.J.
        • Davidson W.S.
        Proteomic characterization of human plasma high density lipoprotein fractionated by gel filtration chromatography.
        J. Proteom. Res. 2010; 9: 5239-5249
        • Sun H.
        • Fang H.
        • Chen T.
        • Perkings R.
        • Tong W.
        GOFFA: Gene Ontology for Functional Analysis - software for gene ontology-based functional analysis of genomic and proteomic data.
        BMC Bioinforma. 2006; 7: S23
        • Boulesteix A.L.
        • Strimmer K.
        Partial least squares: a versatile tool for the analysis of high-dimensional genomic data.
        Brief. Bioinform. 2007; 8: 32-44
        • Grygiel-Górniak B.
        Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications–a review.
        Nutr. J. 2014; 13: 17
        • Daynes R.A.
        • Jones D.C.
        Emerging roles of PPARs in inflammation and immunity.
        Nat. Rev. Immunol. 2002; 2: 748-759
        • Chinetti G.
        • Lestavel S.
        • Bocher V.
        • Remaley A.T.
        • Neve B.
        • et al.
        PPAR-alpha and PPAR-gamma activators induce cholesterol removal from human macrophage foam cells through stimulation of the ABCA1 pathway.
        Nat. Med. 2001; 7: 53-58
        • Yang Z.H.
        • Miyahara H.
        • Iwasaki Y.
        • Takeo J.
        • Katayama M.
        Dietary supplementation with long-chain monounsaturated fatty acids attenuates obesity-related metabolic dysfunction and increases expression of PPAR gamma in adipose tissue in type 2 diabetic KK-Ay mice.
        Nutr. Metab. (Lond). 2013; 10: 16
        • Mori T.
        • Kondo H.
        • Hase T.
        • Tokimitsu I.
        • Murase T.
        Dietary fish oil upregulates intestinal lipid metabolism and reduces body weight gain in C57BL/6J mice.
        J. Nutr. 2007; 137: 2629-2634
        • Davidson M.H.
        • Ballantyne C.M.
        • Jacobson T.A.
        • Bittner V.A.
        • Braun L.T.
        • et al.
        Clinical utility of inflammatory markers and advanced lipoprotein testing: advice from an expert panel of lipid specialists.
        J. Clin. Lipidol. 2011; 5: 338-367
        • Keene D.
        • Price C.
        • Shun-Shin M.J.
        • Francis D.P.
        Effect on cardiovascular risk of high density lipoprotein targeted drug treatments niacin, fibrates, and CETP inhibitors: meta-analysis of randomised controlled trials including 117,411 patients.
        BMJ. 2014; 349: g4379
        • Shah A.S.
        • Tan L.
        • Long J.L.
        • Davidson W.S.
        Proteomic diversity of high density lipoproteins: our emerging understanding of its importance in lipid transport and beyond.
        J. Lipid Res. 2013; 54: 2575-2585
        • Carter A.M.
        Complement activation: an emerging player in the pathogenesis of cardiovascular disease.
        Sci. (Cairo). 2012; 2012: 402783
        • Park S.
        • Mathis K.W.
        • Lee I.K.
        The physiological roles of apolipoprotein J/clusterin in metabolic and cardiovascular diseases.
        Rev. Endocr. Metab. Disord. 2014; 15: 45-53