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Multiple miRNA Regulation of Lipoprotein Lipase

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Handbook of Nutrition, Diet, and Epigenetics

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Abstract

Lipoprotein lipase (LPL) is the key enzyme involved in the intravascular lipolysis of triglyceride (TG)-rich lipoproteins. The regulation of LPL expression and activity is complexed, tightly regulated by hormonal, nutritional, and genetic mechanisms, which remain partially unknown. LPL is highly regulated at a posttranscriptional level that could involve miRNA. miR-27 and miR-29 families are the most studied miRNAs responsible for a decreased LPL expression, mainly in adipose tissue but also in hepatocytes. These miRNAs and several others, miR-467 and miR-590, have been shown to directly target LPL in macrophages and prevent atherosclerosis in animal models. Moreover, a LPL haplotype associated with lower TG was shown to disrupt several miRNA-binding sites. LPL activity can also indirectly be regulated by miRNA which regulates the expression of its cofactors such as APOA5 and ANGPTL3/4.

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Abbreviations

Angptl:

Angiopoietin-like protein

Apo:

Apolipoprotein

FA:

Fatty acids

GPIHBP1:

Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1

HTG:

Hypertriglyceridemia

LPL:

Lipoprotein lipase

miRNA:

MicroRNA

SNP:

Single-nucleotide polymorphism

TG:

Triglycerides

TGRL:

Triglyceride-rich lipoproteins

UTR:

Untranslated region

References

  • Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233

    Article  CAS  Google Scholar 

  • Bouvy-Liivrand M, Heinaniemi M, John E et al (2014) Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis. RNA Biol 11:76–91

    Article  CAS  Google Scholar 

  • Can U, Buyukinan M, Yerlikaya FH (2016) The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity. Pediatr Obes 11:228–234

    Article  CAS  Google Scholar 

  • Caussy C, Charrière S, Marçais C et al (2014) An APOA5 3′ UTR variant associated with plasma triglycerides triggers APOA5 downregulation by creating a functional miR-485-5p binding site. Am J Hum Genet 94:129–134

    Article  CAS  Google Scholar 

  • Caussy C, Charrière S, Meirhaeghe A et al (2016) Multiple microRNA regulation of lipoprotein lipase gene abolished by 3′UTR polymorphisms in a triglyceride-lowering haplotype harboring p.Ser474Ter. Atherosclerosis 246:280–286

    Article  CAS  Google Scholar 

  • Charriere S, Bernard S, Aqallal M et al (2008) Association of APOA5 -1131T>C and S19W gene polymorphisms with both mild hypertriglyceridemia and hyperchylomicronemia in type 2 diabetic patients. Clin Chim Acta 394:99–103

    Article  CAS  Google Scholar 

  • Charrière S, Cugnet C, Guitard M et al (2009) Modulation of phenotypic expression of APOA5 Q97X and L242P mutations. Atherosclerosis 207:150–156

    Article  Google Scholar 

  • Chen T, Li Z, Tu J et al (2011) MicroRNA-29a regulates pro-inflammatory cytokine secretion and scavenger receptor expression by targeting LPL in oxLDL-stimulated dendritic cells. FEBS Lett 585:657–663

    Article  CAS  Google Scholar 

  • Chen WJ, Yin K, Zhao GJ et al (2012) The magic and mystery of microRNA-27 in atherosclerosis. Atherosclerosis 222:314–323

    Article  CAS  Google Scholar 

  • Corella D, Sorlí JV, Estruch R et al (2014) MicroRNA-410 regulated lipoprotein lipase variant rs13702 is associated with stroke incidence and modulated by diet in the randomized controlled PREDIMED trial. Am J Clin Nutr 100:719–731

    Article  CAS  Google Scholar 

  • Dancer M, Caussy C, Di Filippo M et al (2016) Lack of evidence for a liver or intestinal miRNA regulation involved in the hypertriglyceridemic effect of APOC3 3′UTR variant SstI. Atherosclerosis 255:6–10

    Article  CAS  Google Scholar 

  • Deng Z, He Y, Yang X et al (2017) MicroRNA-29: a crucial player in fibrotic disease. Mol Diagn Ther 21:285–294

    Article  CAS  Google Scholar 

  • Dewey FE, Gusarova V, O’Dushlaine C et al (2016) Inactivating variants in ANGPTL4 and risk of coronary artery disease. N Engl J Med 374:1123–1133

    Article  CAS  Google Scholar 

  • Dijk W, Kersten S (2016) Regulation of lipid metabolism by angiopoietin-like proteins. Curr Opin Lipidol 27:249–256

    Article  CAS  Google Scholar 

  • Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19:586–593

    Article  CAS  Google Scholar 

  • Gong J, Tong Y, Zhang HM et al (2012) Genome-wide identification of SNPs in microRNA genes and the SNP effects on microRNAtarget binding and biogenesis. Hum Mutat 33:254–263

    Article  CAS  Google Scholar 

  • Groenendijk M, Cantor RM, de Bruin TW et al (2001) The apoAI-CIII-AIV gene cluster. Atherosclerosis 157:1–11

    Article  CAS  Google Scholar 

  • Grosskopf I, Baroukh N, Lee SJ et al (2005) Apolipoprotein A-V deficiency results in marked hypertriglyceridemia attributable to decreased lipolysis of triglyceriderich lipoproteins and removal of their remnants. Arterioscler Thromb Vasc Biol 25:2573–2579

    Article  CAS  Google Scholar 

  • He A, Zhu L, Gupta N et al (2007) Overexpression of micro ribonucleic acid 29, highly up-regulated in diabetic rats, leads to insulin resistance in 3T3-L1 adipocytes. Mol Endocrinol 21:2785–2794

    Article  CAS  Google Scholar 

  • He PP, Ouyang XP, Tang YY et al (2014) MicroRNA-590 attenuates lipid accumulation and pro-inflammatory cytokine secretion by targeting lipoprotein lipase gene in human THP-1 macrophages. Biochimie 106:81–90

    Article  CAS  Google Scholar 

  • He PP, OuYang XP, Li Y et al (2015) MicroRNA-590 inhibits lipoprotein lipase expression and prevents atherosclerosis in apoE knockout mice. PLoS One 10:e0138788

    Article  Google Scholar 

  • He Z, Hu C, Jia W (2016) miRNAs in non-alcoholic fatty liver disease. Front Med 10:389–396

    Article  Google Scholar 

  • Hegele RA, Ginsberg HN, Chapman MJ et al (2014) The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2:655–666

    Article  CAS  Google Scholar 

  • Hensley LL, Ranganathan G, Wagner EM et al (2003) Transgenic mice expressing lipoprotein lipase in adipose tissue. Absence of the proximal 3′-untranslated region causes translational upregulation. J Biol Chem 278:32702–32709

    Article  CAS  Google Scholar 

  • Herrera BM, Lockstone HE, Taylor JM et al (2010) Global microRNA expression profiles in insulin target tissues in a spontaneous rat model of type 2 diabetes. Diabetologia 53:1099–1109

    Article  CAS  Google Scholar 

  • Hoffer MJ, Sijbrands EJ, De Man FH et al (1998) Increased risk for endogenous hypertriglyceridaemia is associated with an apolipoprotein C3 haplotype specified by the SstI polymorphism. Eur J Clin Investig 28:807–812

    Article  CAS  Google Scholar 

  • Hu SL, Cui GL, Huang J et al (2016) An APOC3 3′UTR variant associated with plasma triglycerides levels and coronary heart disease by creating a functional miR-4271 binding site. Sci Rep 6:32700

    Article  CAS  Google Scholar 

  • Jin X, Ye YF, Chen SH et al (2009) MicroRNA expression pattern in different stages of nonalcoholic fatty liver disease. Dig Liver Dis 41:289–297

    Article  CAS  Google Scholar 

  • Karbiener M, Fischer C, Nowitsch S et al (2009) microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun 390:247–251

    Article  CAS  Google Scholar 

  • Kersten S (2014) Physiological regulation of lipoprotein lipase. Biochim Biophys Acta 1841:919–933

    Article  CAS  Google Scholar 

  • Kim SY, Kim AY, Lee HW et al (2010) miR-27a is a negative regulator of adipocyte differentiation via suppressing PPARgamma expression. Biochem Biophys Res Commun 392:323–328

    Article  CAS  Google Scholar 

  • Kriegel AJ, Liu Y, Fang Y et al (2012) The miR-29 family: genomics, cell biology, and relevance to renal and cardiovascular injury. Physiol Genomics 44:237–244

    Article  CAS  Google Scholar 

  • Kristensen MM, Davidsen PK, Vigelsø A et al (2017) miRNAs in human subcutaneous adipose tissue: effects of weight loss induced by hypocaloric diet and exercise. Obesity (Silver Spring) 25:572–580

    Article  CAS  Google Scholar 

  • Lan G, Xie W, Li L et al (2016) MicroRNA-134 actives lipoprotein lipase-mediated lipid accumulation and inflammatory response by targeting angiopoietin-like 4 in THP-1 macrophages. Biochem Biophys Res Commun 472:410–417

    Article  CAS  Google Scholar 

  • Li Y, He PP, Zhang DW et al (2014) Lipoprotein lipase: from gene to atherosclerosis. Atherosclerosis 237:597–608

    Article  CAS  Google Scholar 

  • Marçais C, Bernard S, Merlin M et al (2000) Severe hypertriglyceridaemia in type II diabetes: involvement of apoC-III Sst-I polymorphism, LPL mutations and apo E3 deficiency. Diabetologia 43:1346–1352

    Article  Google Scholar 

  • Marçais C, Verges B, Charrière S et al (2005) Apoa5 Q139X truncation predisposes to late-onset hyperchylomicronemia due to lipoprotein lipase impairment. J Clin Invest 115:2862–2869

    Article  Google Scholar 

  • Mattis AN, Song G, Hitchner K et al (2015) A screen in mice uncovers repression of lipoprotein lipase by microRNA-29a as a mechanism for lipid distribution away from the liver. Hepatology 61:141–152

    Article  CAS  Google Scholar 

  • Merkel M, Loeffler B, Kluger M et al (2005) Apolipoprotein AV accelerates plasma hydrolysis of triglyceride-rich lipoproteins by interaction with proteoglycan-bound lipoprotein lipase. J Biol Chem 280:21553–21560

    Article  CAS  Google Scholar 

  • Musunuru K, Pirruccello JP, Do R et al (2010) Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 363:2220–2227

    Article  CAS  Google Scholar 

  • Pardina E, Baena-Fustegueras JA, Llamas R et al (2009) Lipoprotein lipase expression in livers of morbidly obese patients could be responsible for liver steatosis. Obes Surg 19:608–616

    Article  Google Scholar 

  • Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173

    Article  CAS  Google Scholar 

  • Pennacchio LA, Olivier M, Hubacek JA et al (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038

    Article  CAS  Google Scholar 

  • Ranganathan G, Li C, Kern PA (2000) The translational regulation of lipoprotein lipase in diabetic rats involves the 3′-untranslated region of the lipoprotein lipase mRNA. J Biol Chem 275:40986–40991

    Article  CAS  Google Scholar 

  • Richardson K, Louie-Gao Q, Arnett DK et al (2011) The PLIN4 variant rs8887 modulates obesity related phenotypes in humans through creation of a novel miR-522 seed site. PLoS One 6:e17944

    Article  CAS  Google Scholar 

  • Richardson K, Nettleton JA, Rotllan N et al (2013) Gain-of-function lipoprotein lipase variant rs13702 modulates lipid traits through disruption of a microRNA-410 seed site. Am J Hum Genet 92:5–14

    Article  CAS  Google Scholar 

  • Roderburg C, Urban GW, Bettermann K et al (2011) Micro-RNA profiling reveals a role for miR-29 in human and murine liver fibrosis. Hepatology 53:209–218

    Article  CAS  Google Scholar 

  • Tian GP, Chen WJ, He PP et al (2012) MicroRNA-467b targets LPL gene in RAW 264.7 macrophages and attenuates lipid accumulation and proinflammatory cytokine secretion. Biochimie 94:2749–2755

    Article  CAS  Google Scholar 

  • Tian GP, Tang YY, He PP et al (2014) The effects of miR-467b on lipoprotein lipase (LPL) expression, pro-inflammatory cytokine, lipid levels and atherosclerotic lesions in apolipoprotein E knockout mice. Biochem Biophys Res Commun 443:428–434

    Article  CAS  Google Scholar 

  • Vickers KC, Shoucri BM, Levin MG et al (2013) MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia. Hepatology 57:533–542

    Article  CAS  Google Scholar 

  • Willer CJ, Sanna S, Jackson AU et al (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40:161–169

    Article  CAS  Google Scholar 

  • Xie W, Li L, Zhang M et al (2016) MicroRNA-27 prevents atherosclerosis by suppressing lipoprotein lipase-induced lipid accumulation and inflammatory response in apolipoprotein E knockout mice. PLoS One 11:e0157085

    Article  Google Scholar 

  • Zhang M, Wu JF, Chen WJ et al (2014) MicroRNA-27a/b regulates cellular cholesterol efflux, influx and esterification/hydrolysis in THP-1 macrophages. Atherosclerosis 234:54–64

    Article  CAS  Google Scholar 

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Authors and Affiliations

  1. Claude Bernard University, Lyon, France

    Sybil Charriere & Philippe Moulin

  2. Department of Endocrinology, Diabetology, Metabolic Diseases and Nutrition, Cardiovascular Hospital Louis Pradel, Bron Cedex, France

    Sybil Charriere & Philippe Moulin

Authors
  1. Sybil Charriere
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  2. Philippe Moulin
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Corresponding author

Correspondence to Sybil Charriere .

Editor information

Editors and Affiliations

  1. School of Life Sciences, University of Westminster, London, UK

    Vinood B. Patel

  2. Diabetes and Nutritional Sciences Research Division, Faculty of Life Sciences and Medicine, King’s College London, London, UK

    Victor R. Preedy

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Charriere, S., Moulin, P. (2019). Multiple miRNA Regulation of Lipoprotein Lipase. In: Patel, V., Preedy, V. (eds) Handbook of Nutrition, Diet, and Epigenetics. Springer, Cham. https://doi.org/10.1007/978-3-319-55530-0_98

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  • DOI: https://doi.org/10.1007/978-3-319-55530-0_98

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  • Publisher Name: Springer, Cham

  • Print ISBN: 978-3-319-55529-4

  • Online ISBN: 978-3-319-55530-0

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