Effects of statins and exercise on postprandial lipoproteins in metabolic syndrome vs metabolically healthy individuals

Laura Alvarez-Jimenez, Alfonso Moreno-Cabañas, Miguel Ramirez-Jimenez, Felix Morales-Palomo, Juan F Ortega, Ricardo Mora-Rodriguez, Laura Alvarez-Jimenez, Alfonso Moreno-Cabañas, Miguel Ramirez-Jimenez, Felix Morales-Palomo, Juan F Ortega, Ricardo Mora-Rodriguez

Abstract

Aims: To determine if the combination of exercise and statin could normalize postprandial triglyceridaemia (PPTG) in hypercholesteraemic individuals.

Methods: Eight hypercholesteraemic (blood cholesterol 182 ± 38 mg dL-1 ; low-density lipoprotein-cholesterol [LDL-c] 102 ± 32 mg dL-1 ) overweight (body mass index 30 ± 4 kg m-2 ) individuals with metabolic syndrome (MetS) were compared to a group of 8 metabolically healthy (MetH) controls (blood cholesterol 149 ± 23 mg dL-1 ; LDL-c 77 ± 23 mg dL-1 , and body mass index 23 ± 2 kg m-2 ). Each group underwent 2 PPTG tests, either 14 hours after a bout of intense exercise or without previous exercise. Additionally, MetS individuals were tested 96 hours after withdrawal of their habitual statin medication to study medication effects.

Results: A bout of exercise before the test meal did not reduce PPTG in MetS (P = .347), but reduced PPTG by 46% in MetH (413 ± 267 to 224 ± 142 mg dL-1 for 5 h incremental area under the curve; P = .02). In both trials (i.e., either after a bout of intense exercise or without previous exercise), statin withdrawal in MetS greatly increased PPTG (average 65%; P < .01), mean LDL-c (average 25%; P < .01), total cholesterol (average 16%; P < .01) and apolipoprotein (Apo) B48 (24%; P < .01), without interference from exercise. However, Apo B100 was not affected by statin withdrawal.

Conclusion: Hypercholesteraemic MetS individuals (compared to MetH controls) fail to show an effect of exercise on reducing PPTG. However, chronic statin medication blunts the elevations in triglyceride after a fat meal (i.e., incremental area under the curve of PPTG) reducing their cardiovascular risk associated with their atherogenic dyslipidaemia. Statin decreases PPTG by reducing the secretion or accelerating the catabolism of intestinal Apo B48.

Trial registration: ClinicalTrials.gov NCT03019796.

Keywords: apolipoprotein B48; healthy controls; hydroxymethylglutaryl-CoA reductase inhibitors; hypercholesterolaemia; metabolic syndrome X; postprandial lipaemia.

© 2020 The British Pharmacological Society.

References

REFERENCES

    1. Francisco G, Hernandez C, Simo R. Serum markers of vascular inflammation in dyslipemia. Clin Chim Acta. 2006;369(1):1-16.
    1. Mamo JC, Proctor SD, Smith D. Retention of chylomicron remnants by arterial tissue; importance of an efficient clearance mechanism from plasma. Atherosclerosis. 1998;141(Suppl 1):S63-S69.
    1. Vogel RA, Corretti MC, Plotnick GD. Effect of a single high-fat meal on endothelial function in healthy subjects. Am J Cardiol. 1997;79(3):350-354.
    1. Shojaee-Moradie F, Ma Y, Lou S, Hovorka R, Umpleby AM. Prandial hypertriglyceridemia in metabolic syndrome is due to an overproduction of both chylomicron and VLDL triacylglycerol. Diabetes. 2013;62(12):4063-4069.
    1. Gill JM, Mees GP, Frayn KN, Hardman AE. Moderate exercise, postprandial lipaemia and triacylglycerol clearance. Eur J Clin Invest. 2001;31(3):201-207.
    1. Brown MS, Goldstein JL. A receptor-mediated pathway for cholesterol homeostasis. Science. 1986;232(4746):34-47.
    1. Mora-Rodriguez R, Ortega JF, Morales-Palomo F, Ramirez-Jimenez M, Moreno-Cabanas A. Effects of statins therapy and exercise on postprandial triglycerides in overweight individuals with hypercholesterolemia. Br J Clin Pharmacol. 2020;1-11.
    1. Parhofer KG, Laubach E, Barrett PH. Effect of atorvastatin on postprandial lipoprotein metabolism in hypertriglyceridemic patients. J Lipid Res. 2003;44(6):1192-1198.
    1. Schoonjans K, Peinado-Onsurbe J, Fruchart JC, Tailleux A, Fievet C, Auwerx J. 3-Hydroxy-3-methylglutaryl CoA reductase inhibitors reduce serum triglyceride levels through modulation of apolipoprotein C-III and lipoprotein lipase. FEBS Lett. 1999;452(3):160-164.
    1. Alberti KG, Eckel RH, Grundy SM, et al. Harmonizing the metabolic syndrome: a joint interim statement of the international diabetes federation task force on epidemiology and prevention; National Heart, Lung, and Blood Institute; American Heart Association; world heart federation; international atherosclerosis society; and International Association for the Study of obesity. Circulation. 2009;120:1640-1645.
    1. Kosoglou T, Statkevich P, Johnson-Levonas AO, Paolini JF, Bergman AJ, Alton KB. Ezetimibe: a review of its metabolism, pharmacokinetics and drug interactions. Clin Pharmacokinet. 2005;44(5):467-494.
    1. Schachter M. Chemical, pharmacokinetic and pharmacodynamic properties of statins: an update. Fundam Clin Pharmacol. 2005;19(1):117-125.
    1. Moreno-Cabanas A, Ortega JF, Morales-Palomo F, Ramirez-Jimenez M, Mora-Rodriguez R. Importance of a verification test to accurately assess VO2 max in unfit individuals with obesity. Scand J Med Sci Sports. 2020;30(3):583-590.
    1. Freese EC, Gist NH, Cureton KJ. Effect of prior exercise on postprandial lipemia: an updated quantitative review. J Appl Physiol. 2014;116(1):67-75.
    1. Maraki MI, Sidossis LS. The latest on the effect of prior exercise on postprandial lipaemia. Sports Med. 2013;43(6):463-481.
    1. Matthews JN, Altman DG, Campbell MJ, Royston P. Analysis of serial measurements in medical research. BMJ. 1990;300(6719):230-235.
    1. Friedewald WT, Levy RI, Fredrickson DS. Estimation of the concentration of low-density lipoprotein cholesterol in plasma, without use of the preparative ultracentrifuge. Clin Chem. 1972;18(6):499-502.
    1. Mestek ML, Plaisance EP, Ratcliff LA, Taylor JK, Wee SO, Grandjean PW. Aerobic exercise and postprandial lipemia in men with the metabolic syndrome. Med Sci Sports Exerc. 2008;40(12):2105-2111.
    1. Zhang JQ, Ji LL, Fretwell VS, Nunez G. Effect of exercise on postprandial lipemia in men with hypertriglyceridemia. Eur J Appl Physiol. 2006;98(6):575-582.
    1. MacEneaney OJ, Harrison M, O'Gorman DJ, Pankratieva EV, O'Connor PL, Moyna NM. Effect of prior exercise on postprandial lipemia and markers of inflammation and endothelial activation in normal weight and overweight adolescent boys. Eur J Appl Physiol. 2009;106(5):721-729.
    1. Gill JM, Al-Mamari A, Ferrell WR, et al. Effects of prior moderate exercise on postprandial metabolism and vascular function in lean and centrally obese men. J Am Coll Cardiol. 2004;44(12):2375-2382.
    1. Cox-York KA, Sharp TA, Stotz SA, Bessesen DH, Pagliassotti MJ, Horton TJ. The effects of sex, metabolic syndrome and exercise on postprandial lipemia. Metabolism. 2013;62(2):244-254.
    1. Dalgaard M, Thomsen C, Hermansen K. Effects of one single bout of low-intensity exercise on postprandial lipaemia in type 2 diabetic men. Br J Nutr. 2004;92(3):469-476.
    1. Gill JM, Al-Mamari A, Ferrell WR, et al. Effect of prior moderate exercise on postprandial metabolism in men with type 2 diabetes: heterogeneity of responses. Atherosclerosis. 2007;194(1):134-143.
    1. Parhofer KG, Barrett PH, Schwandt P. Atorvastatin improves postprandial lipoprotein metabolism in normolipidemlic subjects. J Clin Endocrinol Metab. 2000;85(11):4224-4230.
    1. Dane-Stewart CA, Watts GF, Pal S, et al. Effect of atorvastatin on apolipoprotein B48 metabolism and low-density lipoprotein receptor activity in normolipidemic patients with coronary artery disease. Metabolism. 2003;52(10):1279-1286.
    1. Chan DC, Watts GF, Somaratne R, Wasserman SM, Scott R, Barrett PHR. Comparative effects of PCSK9 (Proprotein convertase Subtilisin/Kexin type 9) inhibition and statins on postprandial triglyceride-rich lipoprotein metabolism. Arterioscler Thromb Vasc Biol. 2018;38(7):1644-1655.
    1. Lamon-Fava S, Diffenderfer MR, Barrett PH, et al. Effects of different doses of atorvastatin on human apolipoprotein B-100, B-48, and A-I metabolism. J Lipid Res. 2007;48(8):1746-1753.
    1. Schneider JG, von Eynatten M, Parhofer KG, et al. Atorvastatin improves diabetic dyslipidemia and increases lipoprotein lipase activity in vivo. Atherosclerosis. 2004;175(2):325-331.
    1. Battula SB, Fitzsimons O, Moreno S, et al. Postprandial apolipoprotein B48-and B100-containing lipoproteins in type 2 diabetes: do statins have a specific effect on triglyceride metabolism? Metabolism. 2000;49(8):1049-1054.
    1. Williams ML, Menon GK, Hanley KP. HMG-CoA reductase inhibitors perturb fatty acid metabolism and induce peroxisomes in keratinocytes. J Lipid Res. 1992;33:193-208.

Source: PubMed

Sponsors and Collaborators

Medical Conditions

Drug Interventions

3
Subscribe