Multiple miRNA Regulation of Lipoprotein Lipase

  • Sybil CharriereEmail author
  • Philippe Moulin
Reference work entry


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.


Adipose tissue Angtpl3 Angtl4 Apolipoprotein A5 Apolipoprotein C3 Lipoprotein lipase Macrophages miR-27 miR-29 miRNA Triglycerides 

List of Abbreviations


Angiopoietin-like protein




Fatty acids


Glycosylphosphatidylinositol-anchored high-density lipoprotein-binding protein 1




Lipoprotein lipase




Single-nucleotide polymorphism




Triglyceride-rich lipoproteins


Untranslated region


  1. Bartel DP (2009) MicroRNAs: target recognition and regulatory functions. Cell 136:215–233CrossRefGoogle Scholar
  2. Bouvy-Liivrand M, Heinaniemi M, John E et al (2014) Combinatorial regulation of lipoprotein lipase by microRNAs during mouse adipogenesis. RNA Biol 11:76–91CrossRefGoogle Scholar
  3. Can U, Buyukinan M, Yerlikaya FH (2016) The investigation of circulating microRNAs associated with lipid metabolism in childhood obesity. Pediatr Obes 11:228–234CrossRefGoogle Scholar
  4. 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 94:129–134CrossRefGoogle Scholar
  5. 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 246:280–286CrossRefGoogle Scholar
  6. 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 394:99–103CrossRefGoogle Scholar
  7. Charrière S, Cugnet C, Guitard M et al (2009) Modulation of phenotypic expression of APOA5 Q97X and L242P mutations. Atherosclerosis 207:150–156CrossRefGoogle Scholar
  8. 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 585:657–663CrossRefGoogle Scholar
  9. Chen WJ, Yin K, Zhao GJ et al (2012) The magic and mystery of microRNA-27 in atherosclerosis. Atherosclerosis 222:314–323CrossRefGoogle Scholar
  10. 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 100:719–731CrossRefGoogle Scholar
  11. 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 255:6–10CrossRefGoogle Scholar
  12. Deng Z, He Y, Yang X et al (2017) MicroRNA-29: a crucial player in fibrotic disease. Mol Diagn Ther 21:285–294CrossRefGoogle Scholar
  13. Dewey FE, Gusarova V, O’Dushlaine C et al (2016) Inactivating variants in ANGPTL4 and risk of coronary artery disease. N Engl J Med 374:1123–1133CrossRefGoogle Scholar
  14. Dijk W, Kersten S (2016) Regulation of lipid metabolism by angiopoietin-like proteins. Curr Opin Lipidol 27:249–256CrossRefGoogle Scholar
  15. Fabian MR, Sonenberg N (2012) The mechanics of miRNA-mediated gene silencing: a look under the hood of miRISC. Nat Struct Mol Biol 19:586–593CrossRefGoogle Scholar
  16. 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 33:254–263CrossRefGoogle Scholar
  17. Groenendijk M, Cantor RM, de Bruin TW et al (2001) The apoAI-CIII-AIV gene cluster. Atherosclerosis 157:1–11CrossRefGoogle Scholar
  18. 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 25:2573–2579CrossRefGoogle Scholar
  19. 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 21:2785–2794CrossRefGoogle Scholar
  20. 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 106:81–90CrossRefGoogle Scholar
  21. 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:e0138788CrossRefGoogle Scholar
  22. He Z, Hu C, Jia W (2016) miRNAs in non-alcoholic fatty liver disease. Front Med 10:389–396CrossRefGoogle Scholar
  23. Hegele RA, Ginsberg HN, Chapman MJ et al (2014) The polygenic nature of hypertriglyceridaemia: implications for definition, diagnosis, and management. Lancet Diabetes Endocrinol 2:655–666CrossRefGoogle Scholar
  24. 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 278:32702–32709CrossRefGoogle Scholar
  25. 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 53:1099–1109CrossRefGoogle Scholar
  26. 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 28:807–812CrossRefGoogle Scholar
  27. 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 6:32700CrossRefGoogle Scholar
  28. Jin X, Ye YF, Chen SH et al (2009) MicroRNA expression pattern in different stages of nonalcoholic fatty liver disease. Dig Liver Dis 41:289–297CrossRefGoogle Scholar
  29. Karbiener M, Fischer C, Nowitsch S et al (2009) microRNA miR-27b impairs human adipocyte differentiation and targets PPARgamma. Biochem Biophys Res Commun 390:247–251CrossRefGoogle Scholar
  30. Kersten S (2014) Physiological regulation of lipoprotein lipase. Biochim Biophys Acta 1841:919–933CrossRefGoogle Scholar
  31. 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 392:323–328CrossRefGoogle Scholar
  32. 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 44:237–244CrossRefGoogle Scholar
  33. 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) 25:572–580CrossRefGoogle Scholar
  34. 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 472:410–417CrossRefGoogle Scholar
  35. Li Y, He PP, Zhang DW et al (2014) Lipoprotein lipase: from gene to atherosclerosis. Atherosclerosis 237:597–608CrossRefGoogle Scholar
  36. 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 43:1346–1352CrossRefGoogle Scholar
  37. 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 115:2862–2869CrossRefGoogle Scholar
  38. 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 61:141–152CrossRefGoogle Scholar
  39. 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 280:21553–21560CrossRefGoogle Scholar
  40. Musunuru K, Pirruccello JP, Do R et al (2010) Exome sequencing, ANGPTL3 mutations, and familial combined hypolipidemia. N Engl J Med 363:2220–2227CrossRefGoogle Scholar
  41. 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 19:608–616CrossRefGoogle Scholar
  42. Pennacchio LA, Olivier M, Hubacek JA et al (2001) An apolipoprotein influencing triglycerides in humans and mice revealed by comparative sequencing. Science 294:169–173CrossRefGoogle Scholar
  43. Pennacchio LA, Olivier M, Hubacek JA et al (2002) Two independent apolipoprotein A5 haplotypes influence human plasma triglyceride levels. Hum Mol Genet 11:3031–3038CrossRefGoogle Scholar
  44. 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 275:40986–40991CrossRefGoogle Scholar
  45. 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:e17944CrossRefGoogle Scholar
  46. 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 92:5–14CrossRefGoogle Scholar
  47. 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 53:209–218CrossRefGoogle Scholar
  48. 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 94:2749–2755CrossRefGoogle Scholar
  49. 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 443:428–434CrossRefGoogle Scholar
  50. Vickers KC, Shoucri BM, Levin MG et al (2013) MicroRNA-27b is a regulatory hub in lipid metabolism and is altered in dyslipidemia. Hepatology 57:533–542CrossRefGoogle Scholar
  51. Willer CJ, Sanna S, Jackson AU et al (2008) Newly identified loci that influence lipid concentrations and risk of coronary artery disease. Nat Genet 40:161–169CrossRefGoogle Scholar
  52. 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:e0157085CrossRefGoogle Scholar
  53. 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 234:54–64CrossRefGoogle Scholar

Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Claude Bernard UniversityLyonFrance
  2. 2.Department of Endocrinology, Diabetology, Metabolic Diseases and NutritionCardiovascular Hospital Louis PradelBron CedexFrance

Personalised recommendations