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Myristic acid is associated to low plasma HDL cholesterol levels in a Mediterranean population and increases HDL catabolism by enhancing HDL particles trapping to cell surface proteoglycans in a liver hepatoma cell model

      Highlights

      • Plasma free fatty acids were correlated with HDL-C in a Sicilian population.
      • Myristic acid resulted inversely correlated with HDL-C levels.
      • Effects of fatty acids on HDL binding to hepatoma cells were evaluated “in vitro”.
      • Myristic acid increased HDL binding by increasing cells proteoglycan matrix.

      Abstract

      Background

      HDL-C plasma levels are modulated by dietary fatty acid (FA), but studies investigating dietary supplementation in FA gave contrasting results. Saturated FA increased HDL-C levels only in some studies. Mono-unsaturated FA exerted a slight effect while poly-unsaturated FA mostly increased plasma HDL-C.

      Aims

      This study presents two aims: i) to investigate the relationship between HDL-C levels and plasma FA composition in a Sicilian population following a “Mediterranean diet”, ii) to investigate if FA that resulted correlated with plasma HDL-C levels in the population study and/or very abundant in the plasma were able to affect HDL catabolism in an “in vitro” model of cultured hepatoma cells (HepG2).

      Results

      plasma HDL-C levels in the population correlated negatively with myristic acid (C14:0, β = −0.24, p < 0.01), oleic acid (C18:1n9, β = −0.22, p < 0.01) and cis-11-Eicosenoic (C20:1n9, β = −0.19, p = 0.01) and positively with palmitoleic acid (C16:1, β = +0.19, p = 0.03). HepG2 cells were conditioned with FA before evaluating HDL binding kinetics, and only C14:0 increased HDL binding by a non-saturable pathway. After removal of heparan sulphate proteoglycans (HSPG) by heparinases HDL binding dropped by 29% only in C14:0 conditioned cells (p < 0.05). C14:0 showed also the highest internalization of HDL-derived cholesteryl esters (CE, +32% p = 0.01 vs. non-conditioned cells).

      Conclusions

      C14:0 was correlated with decreased plasma HDL-C levels in a Mediterranean population. C14:0 might reduce HDL-C levels by increasing HDL trapping to cell surface HSPG and CE stripping from bound HDL. Other mechanisms are to be investigated to explain the effects of other FA on HDL metabolism.

      Keywords

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      References

        • Michas G.
        • Micha R.
        • Zampelas A.
        Dietary fats and cardiovascular disease: putting together the pieces of a complicated puzzle.
        Atherosclerosis. 2014; 234: 320-328
        • Mensink R.P.
        • Zock P.L.
        • Kester A.D.
        • et al.
        Effects of dietary fatty acids and carbohydrates on the ratio of serum total to HDL cholesterol and on serum lipids and apolipoproteins: a meta-analysis of 60 controlled trials.
        Am. J. Clin. Nutr. 2003; 77: 1146e55
        • Mattson F.H.
        • Grundy S.M.
        Comparison of effects of dietary saturated, monounsaturated, and polyunsaturated fatty acids on plasma lipids and lipoproteins in man.
        J. Lipid Res. 1985; 26: 194-202
        • Ordovas J.M.
        • Corella D.
        • Cupples L.A.
        • Demissie S.
        • Kelleher A.
        • Coltell O.
        • Wilson P.W.
        • Schaefer E.J.
        • Tucker K.
        Polyunsaturated fatty acids modulate the effects of the APOA1 G-A polymorphism on HDL-cholesterol concentrations in a sex-specific manner: the Framingham Study.
        Am. J. Clin. Nutr. 2002; 75: 38-46
        • Brousseau M.E.
        • Ordovas J.M.
        • Osada J.
        • Fasulo J.
        • Robins S.J.
        • Nicolosi R.J.
        • Schaefer E.J.
        Dietary monounsaturated and polyunsaturated fatty acids are comparable in their effects on hepatic apolipoprotein mRNA abundance and liver lipid concentrations when substituted for saturated fatty acids in cynomolgus monkeys.
        J. Nutr. 1995 Mar; 125: 425-436
        • Giron M.D.
        • Mataix F.J.
        • Suarez M.D.
        Long-term effects of dietary monounsaturated and polyunsaturated fatty acids on plasma lipids in dogs.
        Arch. Int. Physiol. Biochim. Biophys. 1992; 100: 321-326
        • von Eckardstein A.
        • Hersberger M.
        • Rohrer L.
        Current understanding of the metabolism and biological actions of HDL.
        Curr. Opin. Clin. Nutr. Metab. Care. 2005; 8: 147-152
        • Uehara Y.
        • Miura S.
        • von Eckardstein A.
        • Abe S.
        • Fujii A.
        • Matsuo Y.
        • Rust S.
        • Lorkowski S.
        • Assmann G.
        • Yamada T.
        • Saku K.
        Unsaturated fatty acids suppress the expression of the ATP-binding cassette transporter G1 (ABCG1) and ABCA1 genes via an LXR/RXR responsive element.
        Atherosclerosis. 2007; 191: 11-21
        • Michaud S.E.
        • Renier G.
        Direct regulatory effect of fatty acids on macrophage lipoprotein lipase: potential role of PPARs.
        Diabetes. 2001; 50: 660-666
        • Lagrost L.
        Regulation of cholesteryl ester transfer protein (CETP) activity: review of in vitro and in vivo studies.
        Biochim. Biophys. Acta. 1994 Dec 8; 1215: 209-236
        • Botma G.J.
        • van Deursen D.
        • Vieira D.
        • van Hoek M.
        • Jansen H.
        • Verhoeven A.J.
        Sterol-regulatory-element binding protein inhibits upstream stimulatory factor-stimulated hepatic lipase gene expression.
        Atherosclerosis. 2005; 179: 61-67
        • Keller H.
        • Dreyer C.
        • Medin J.
        • Mahfoudi A.
        • Ozato K.
        • Wahli W.
        Fatty acids and retinoids control lipid metabolism through activation of peroxisome proliferator-activated receptor-retinoid X receptor heterodimers.
        Proc. Natl. Acad. Sci. U. S. A. 1993; 90: 2160-2164
        • Malerød L.
        • Sporstøl M.
        • Juvet L.K.
        • MoU.S.A.vi A.
        • Gjøen T.
        • Berg T.
        Hepatic scavenger receptor class B, type I is stimulated by peroxisome proliferator-activated receptor gamma and hepatocyte nuclear factor 4alpha.
        Biochem. Biophys. Res. Commun. 2003 Jun 6; 305: 557-565
        • Sheril A.
        • Jeyakumar S.M.
        • Jayashree T.
        • Giridharan N.V.
        • Vajreswari A.
        Impact of feeding polyunsaturated fatty acids on cholesterol metabolism of dyslipidemic obese rats of WNIN/GR-Ob strain.
        Atherosclerosis. 2009 May; 204: 136-140
        • Barbagallo C.M.
        • Cavera G.
        • Sapienza M.
        • Noto D.
        • Cefalù A.B.
        • Polizzi F.
        • Onorato F.
        • Rini G.
        • Di Fede G.
        • Pagano M.
        • Montalto G.
        • Rizzo M.
        • Descovich G.
        • Notarbartolo A.
        • Averna M.R.
        Nutritional characteristics of a rural Southern Italy population: the Ventimiglia di Sicilia Project.
        J. Am. Coll. Nutr. 2002 Dec; 21: 523-529
        • Noto D.
        • Barbagallo C.M.
        • Cefalù A.B.
        • Falletta A.
        • Sapienza M.
        • Cavera G.
        • Amato S.
        • Pagano M.
        • Maggiore M.
        • Carroccio A.
        • Notarbartolo A.
        • Averna M.R.
        The metabolic syndrome predicts cardiovascular events in subjects with normal fasting glucose: results of a 15 years follow-up in a Mediterranean population.
        Atherosclerosis. 2008 Mar; 197 (Epub 2007 Apr 26): 147-153
        • Lepage G.
        • Roy C.C.
        Specific methylation of plasma nonesterified fatty acids in a one-step reaction.
        J. Lipid Res. 1988 Feb; 29: 227-235
        • Noto D.
        • Rizzo M.
        • Barbagallo C.M.
        • Cefalù A.B.
        • Verde A.L.
        • Fayer F.
        • Notarbartolo A.
        • Averna M.R.
        Low-density lipoproteins generated during an oral fat load in mild hypertriglyceridemic and healthy subjects are smaller, denser, and have an increased low-density lipoprotein receptor binding affinity.
        Metabolism. 2006 Oct; 55: 1308-1316
        • Cefalù A.B.
        • Noto D.
        • Magnolo L.
        • Pinotti E.
        • Gomaraschi M.
        • Martini S.
        • Vigna G.B.
        • Calabresi L.
        • Tarugi P.
        • Averna M.R.
        Novel mutations of CETP gene in Italian subjects with hyperalphalipoproteinemia.
        Atherosclerosis. 2009 May; 204: 202-207
        • Yao H.R.
        • Liu J.
        • Plumeri D.
        • Cao Y.B.
        • He T.
        • Lin L.
        • Li Y.
        • Jiang Y.Y.
        • Li J.
        • Shang J.
        Lipotoxicity in HepG2 cells triggered by free fatty acids.
        Am. J. Transl. Res. 2011 May 15; 3: 284-291
        • Huff M.W.
        • Miller D.B.
        • Wolfe B.M.
        • Connelly P.W.
        • Sawyez C.G.
        Uptake of hypertriglyceridemic very low density lipoproteins and their remnants by HepG2 cells: the role of lipoprotein lipase, hepatic triglyceride lipase, and cell surface proteoglycans.
        J. Lipid Res. 1997; 38: 1318-1333
        • Hunter J.E.
        • Zhang J.
        • Kris-Etherton P.M.
        Cardiovascular disease risk of dietary stearic acid compared with trans, other saturated, and unsaturated fatty acids: a systematic review.
        Am. J. Clin. Nutr. 2010 Jan; 91 (Epub 2009 Nov 25): 46-63https://doi.org/10.3945/ajcn.2009.27661
        • Mayneris-Perxachs J.
        • Guerendiain M.
        • Castellote A.I.
        • Estruch R.
        • Covas M.I.
        • Fitó M.
        • Salas-Salvadó J.
        • Martínez-González M.A.
        • Aros F.
        • Lamuela-Raventós R.M.
        • López-Sabater M.C.
        for PREDIMED Study Investigators. Plasma fatty acid composition, estimated desaturase activities, and their relation with the metabolic syndrome in a population at high risk of cardiovascular disease.
        Clin. Nutr. 2014 Feb; 33: 90-97
        • Dreon D.M.
        • Fernstrom H.A.
        • Campos H.
        • Blanche P.
        • Williams P.T.
        • Krauss R.M.
        Change in dietary saturated fat intake is correlated with change in mass of large low-density-lipoprotein particles in men.
        Am. J. Clin. Nutr. 1998 May; 67: 828-836
        • Tholstrup T.
        • Marckmann P.
        • Vessby B.
        • Sandström B.
        Effect of fats high in individual saturated fatty acids on plasma lipoprotein[a] levels in young healthy men.
        J. Lipid Res. 1995; 36: 1447-1452
        • Camejo G.
        • Hurt-Camejo E.
        • Wiklund O.
        • Bondjers G.
        Association of apo B lipoproteins with arterial proteoglycans: pathological significance and molecular basis.
        Atherosclerosis. 1998; 139: 205-222
        • Loison C.
        • Mendy F.
        • Sérougne C.
        • Lutton C.
        Dietary myristic acid modifies the HDL-cholesterol concentration and liver scavenger receptor BI expression in the hamster.
        Br. J. Nutr. 2002 Mar; 87: 199-210
        • Tholstrup T.
        • Marckmann P.
        • Jespersen J.
        • Sandström B.
        Fat high in stearic acid favorably affects blood lipids and factor VII coagulant activity in comparison with fats high in palmitic acid or high in myristic and lauric acids.
        Am. J. Clin. Nutr. 1994 Feb; 59: 371-377
        • Bérard A.M.
        • Dabadie H.
        • Palos-Pinto A.
        • Dumon M.F.
        • Darmon M.
        Reduction of dietary saturated fatty acids correlates with increased plasma lecithin cholesterol acyltransferase activity in humans.
        Eur. J. Clin. Nutr. 2004 Jun; 58: 881-887