Skip to main content

Advertisement

SpringerLink
Log in

Role of Liver X Receptor in Mastitis Therapy and Regulation of Milk Fat Synthesis

  • Published:
Journal of Mammary Gland Biology and Neoplasia Aims and scope Submit manuscript

Abstract

Mastitis is important disease that causes huge economic losses in the dairy industry. In recent years, antibiotic therapy has become the primary treatment for mastitis, however, due to drug residue in milk and food safety factors, we lack safe and effective drugs for treating mastitis. Therefore, new targets and drugs are urgently needed to control mastitis. LXRα, one of the main members of the nuclear receptor superfamily, is reported to play important roles in metabolism, infection and immunity. Activation of LXRα could inhibit LPS-induced mastitis. Furthermore, LXRα is reported to enhance milk fat production, thus, LXRα may serve as a new target for mastitis therapy and regulation of milk fat synthesis. This review summarizes the effects of LXRα in regulating milk fat synthesis and treatment of mastitis and highlights the potential agonists involved in both issues.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

Similar content being viewed by others

Abbreviations

LXR:

liver X receptor

LPS:

lipopolysaccharide

TLR4:

toll-like receptor 4

NF-κB:

nuclear transcription factor κB

TNF-α:

necrosis factor-α

IL:

interleukin

ABCG1:

Adenosine triphosphate binds to the box subfamily G1 antibody

SREBP1:

sterol regulatory element binding proteins 1c

PPARγ:

peroxisome proliferator activated receptor γ

FASN:

fatty synthase

PRRs:

pattern recognition receptors

PAMPs:

pathogen-associated molecular patterns

LBP:

LPS-binding protein

MD-2:

myeloid differentiation protein-2

CD14:

leukocyte differentiation antigen

MyD88:

myeloid differentiation protein antigen

MAPK:

mitogenactivated protein kinase

IRF3:

interferon regulating factor 3

IFN:

interferon

ABCA1:

ATP-binding cassette transporter A1

ApoA1:

apolipoprotein A1

HDL:

high density lipoprotein

PEG2:

prostaglandin

SSa:

saikosaponina A

RXR:

retinoid x receptor

PLD:

platycodin D

C3G:

cyaniding-3-o-β-glucoside

MFGM:

milk fat globule membrane

ACC:

Acetyl-CoA carboxylase

FAS:

fatty acid synthase

NME-UV:

bovine mammary epithelial cells

Reference

  1. Halasa T, Huijps K, Osteras O, Hogeveen H. Economic effects of bovine mastitis and mastitis management: a review. Vet Q. 2007;29:18–31.

    Article  CAS  PubMed  Google Scholar 

  2. Hughes K, Watson CJ. The mammary microenvironment in mastitis in humans, dairy ruminants, rabbits and rodents: a one health focus. J Mammary Gland Biol Neoplasia. 2018.

  3. Contreras GA, Mastitis RJM. Comparative etiology and epidemiology. J Mammary Gland Biol. 2011;16:339–56.

    Article  Google Scholar 

  4. Steeneveld W, Hogeveen H, Barkema HW, van den Broek J, Huirne RB. The influence of cow factors on the incidence of clinical mastitis in dairy cows. J Dairy Sci. 2008;91:1391–402.

    Article  CAS  PubMed  Google Scholar 

  5. Wellnitz O, Bruckmaier RM. The innate immune response of the bovine mammary gland to bacterial infection. Vet J. 2012;192:148–52.

    Article  CAS  PubMed  Google Scholar 

  6. He X, Wei Z, Zhou E, Chen L, Kou J, Wang J, et al. Baicalein attenuates inflammatory responses by suppressing TLR4 mediated NF-kappaB and MAPK signaling pathways in LPS-induced mastitis in mice. Int Immunopharmacol. 2015;28:470–6.

    Article  CAS  PubMed  Google Scholar 

  7. Hu G, Hong D, Zhang T, Duan H, Wei P, Guo X, et al. Cynatratoside-C from Cynanchum atratum displays anti-inflammatory effect via suppressing TLR4 mediated NF-kappaB and MAPK signaling pathways in LPS-induced mastitis in mice. Chem Biol Interact. 2018;279:187–95.

    Article  CAS  PubMed  Google Scholar 

  8. Zou J, Feng D, Ling WH, Duan RD. Lycopene suppresses proinflammatory response in lipopolysaccharide-stimulated macrophages by inhibiting ROS-induced trafficking of TLR4 to lipid raft-like domains. J Nutr Biochem. 2013;24:1117–22.

    Article  CAS  PubMed  Google Scholar 

  9. Chen M, Beaven S, Tontonoz P. Identification and characterization of two alternatively spliced transcript variants of human liver X receptor alpha. J Lipid Res. 2005;46:2570–9.

    Article  CAS  PubMed  Google Scholar 

  10. Beltowski J, Liver X. Receptors (LXR) as therapeutic targets in dyslipidemia. Cardiovasc Ther. 2008;26:297–316.

    Article  CAS  PubMed  Google Scholar 

  11. Kashiwagi K, Yanagida M, Matsui D, Tanaka M, Sugimoto K, Chen H, et al. Expression of liver X receptors in normal and refractory carcinoma tissues of the human lung and pancreas. Histol Histopathol. 2017:11949.

  12. Cheng S, Liang S, Liu Q, Deng Z, Zhang Y, Du J, et al. Diosgenin prevents high-fat diet-induced rat non-alcoholic fatty liver disease through the AMPK and LXR signaling pathways. Int J Mol Med. 2018;41:1089–95.

    CAS  PubMed  Google Scholar 

  13. Theofilopoulos S, Wang Y, Kitambi SS, Sacchetti P, Sousa KM, Bodin K, et al. Brain endogenous liver X receptor ligands selectively promote midbrain neurogenesis. Nat Chem Biol. 2013;9:126–33.

    Article  CAS  PubMed  Google Scholar 

  14. Yao DW, Luo J, He QY, Xu HF, Li J, Shi HB, et al. Liver X receptor alpha promotes the synthesis of monounsaturated fatty acids in goat mammary epithelial cells via the control of stearoyl-coenzyme A desaturase 1 in an SREBP-1-dependent manner. J Dairy Sci. 2016;99:6391–402.

    Article  CAS  PubMed  Google Scholar 

  15. Lei B, Lei CY. Amelioration of Amyloid beta induced retinal inflammatory responses by a LXR agonist T0901317 is associated with inactivation of the NF-kappa B signaling and NLRP3 Inflammasome. Invest Ophth Vis Sci. 2016;57

  16. Lee JH, Kim H, Park SJ, Woo JH, Joe EH, Jou I. Small heterodimer partner SHP mediates liver X receptor (LXR)-dependent suppression of inflammatory signaling by promoting LXR SUMOylation specifically in astrocytes. Sci Signal. 2016;9

  17. Ding HL, Li Y, Feng YL, Chen J, Zhong X, Wang N, et al. LXR agonist T0901317 upregulates thrombomodulin expression in glomerular endothelial cells by inhibition of nuclear factor-kappa B. Mol Med Rep. 2016;13:4888–96.

    Article  CAS  PubMed  Google Scholar 

  18. Fu YH, Tian Y, Wei ZK, Liu H, Song XJ, Liu WB, et al. Liver X receptor agonist prevents LPS-induced mastitis in mice. Int Immunopharmacol. 2014;22:379–83.

    Article  CAS  PubMed  Google Scholar 

  19. Mansson HL. Fatty acids in bovine milk fat. Food Nutr Res. 2008;52

  20. Harvatine KJ, Boisclair YR, Bauman DE. Liver x receptors stimulate lipogenesis in bovine mammary epithelial cell culture but do not appear to be involved in diet-induced milk fat depression in cows. Physiol Rep. 2014;2:e00266.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Kessler EC, Gross JJ, Bruckmaier RM, Albrecht C. Cholesterol metabolism, transport, and hepatic regulation in dairy cows during transition and early lactation. J Dairy Sci. 2014;97:5481–90.

    Article  CAS  PubMed  Google Scholar 

  22. Chu K, Miyazaki M, Man WC, Ntambi JM. Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation. Mol Cell Biol. 2006;26:6786–98.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  23. Repa JJ, Liang G, Ou J, Bashmakov Y, Lobaccaro JM, Shimomura I, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXRalpha and LXRbeta. Genes Dev. 2000;14:2819–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  24. Yoshikawa T, Ide T, Shimano H, Yahagi N, Amemiya-Kudo M, Matsuzaka T, et al. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. I. PPARs suppress sterol regulatory element binding protein-1c promoter through inhibition of LXR signaling. Mol Endocrinol. 2003;17:1240–54.

    Article  CAS  PubMed  Google Scholar 

  25. Sertznig P, Dunlop T, Seifert M, Tilgen W, Reichrath J. Cross-talk between vitamin D receptor (VDR)- and peroxisome proliferator-activated receptor (PPAR)-signaling in melanoma cells. Anticancer Res. 2009;29:3647–58.

    CAS  PubMed  Google Scholar 

  26. Whitney KD, Watson MA, Collins JL, Benson WG, Stone TM, Numerick MJ, et al. Regulation of cholesterol Homeostasis by the liver X receptors in the central nervous system. Mol Endocrinol. 2002;16:1378–85.

    Article  CAS  PubMed  Google Scholar 

  27. Mandrekar-Colucci S, Landreth GE. Nuclear receptors as therapeutic targets for Alzheimer’s disease. Expert Opin Ther Tar. 2011;15:1085–97.

    Article  CAS  Google Scholar 

  28. Alestas T, Ganceviciene R, Fimmel S, Muller-Decker K, Zouboulis CC. Enzymes involved in the biosynthesis of leukotriene B4 and prostaglandin E2 are active in sebaceous glands. J Mol Med. 2006;84:75–87.

    Article  CAS  PubMed  Google Scholar 

  29. Song C, Kokontis JM, Hiipakka RA, Liao S. Ubiquitous receptor: a receptor that modulates gene activation by retinoic acid and thyroid hormone receptors. Proc Natl Acad Sci U S A. 1994;91:10809–13.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  30. Baranowski M. Biological role of liver X receptors. J Physiol Pharmacol. 2008;59(Suppl 7):31–55.

    PubMed  Google Scholar 

  31. Wojcicka G, Jamroz-Wisniewska A, Horoszewicz K, Beltowski J. Liver X receptors (LXRs). Part I: structure, function, regulation of activity, and role in lipid metabolism. Postepy higieny i medycyny doswiadczalnej. 2007;61:736–59.

    PubMed  Google Scholar 

  32. Gu M, Zhang Y, Liu CH, Wang DS, Feng L, Fan SJ, et al. Morin, a novel liver X receptor / dual antagonist, has potent therapeutic efficacy for nonalcoholic fatty liver diseases. Brit J Pharmacol. 2017;174:3032–44.

    Article  CAS  Google Scholar 

  33. Fongsupa S, Soodvilai S, Muanprasat C, Chatsudthipong V, Soodvilai S. Activation of liver X receptors inhibits cadmium-induced apoptosis of human renal proximal tubular cells. Toxicol Lett. 2015;236:145–53.

    Article  CAS  PubMed  Google Scholar 

  34. Mani O, Sorensen MT, Sejrsen K, Bruckmaier RM, Albrecht C. Differential expression and localization of lipid transporters in the bovine mammary gland during the pregnancy-lactation cycle. J Dairy Sci. 2009;92:3744–56.

    Article  CAS  PubMed  Google Scholar 

  35. Fu Y, Wei Z, Zhou E, Zhang N, Yang Z. Cyanidin-3-O-beta-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model. J Lipid Res. 2014;55:1111–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  36. Wang W, Luo J, Zhong Y, Lin XZ, Shi HB, Zhu JJ, et al. Goat liver X receptor alpha, molecular cloning, functional characterization and regulating fatty acid synthesis in epithelial cells of goat mammary glands. Gene. 2012;505:114–20.

    Article  CAS  PubMed  Google Scholar 

  37. Drogemuller C, Drogemuller M, Leeb T, Mascarello F, Testoni S, Rossi M, et al. Identification of a missense mutation in the bovine ATP2A1 gene in congenital pseudomyotonia of Chianina cattle: An animal model of human Brody disease. Genomics. 2008;92:474–7.

    Article  CAS  PubMed  Google Scholar 

  38. Lund EG, Guileyardo JM, Russell DW. cDNA cloning of cholesterol 24-hydroxylase, a mediator of cholesterol homeostasis in the brain. Proc Natl Acad Sci U S A. 1999;96:7238–43.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Abildayeva K, Jansen PJ, Hirsch-Reinshagen V, Bloks VW, Bakker AHF, Ramaekers FCS, et al. 24(S)-hydroxycholesterol participates in a liver X receptor-controlled pathway in astrocytes that regulates apolipoprotein E-mediated cholesterol efflux. J Biol Chem. 2006;281:12799–808.

    Article  CAS  PubMed  Google Scholar 

  40. Yamanaka K, Saito Y, Yamamori T, Urano Y, Noguchi N. 24(S)-Hydroxycholesterol Induces Neuronal Cell Death through Necroptosis, a form of programmed necrosis. J Biol Chem. 2011;286:24666–73.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  41. Chuu CP, Lin HP. Antiproliferative Effect of LXR Agonists T0901317 and 22(R)-Hydroxycholesterol on multiple human cancer cell lines. Anticancer Res. 2010;30:3643–8.

    CAS  PubMed  Google Scholar 

  42. Viennois E, Pommier AJC, Mouzat K, Oumeddour A, El Hajjaji FZ, Dufour J, et al. Targeting liver X receptors in human health: deadlock or promising trail? Expert Opin Ther Tar. 2011;15:219–32.

    Article  CAS  Google Scholar 

  43. Deng RT, Yang DF, Yang J, Yan BF. Oxysterol 22(R)-hydroxycholesterol induces the expression of the bile salt export pump through nuclear receptor farsenoid X receptor but not liver X receptor. J Pharmacol Exp Ther. 2006;317:317–25.

    Article  CAS  PubMed  Google Scholar 

  44. Koldamova RP, Lefterov LM, Ikonomovic MD, Skoko J, Lefterov PI, Isanskis BA, et al. 22R-Hydroxycholesterol and 9-cis-retinoic acid induce ATP-binding cassette transporter A1 expression and cholesterol efflux in brain cells and decrease amyloid beta secretion. J Biol Chem. 2003;278:13244–56.

    Article  CAS  PubMed  Google Scholar 

  45. Janowski BA, Willy PJ, Devi TR, Falck JR, Mangelsdorf DJ. An oxysterol signalling pathway mediated by the nuclear receptor LXR alpha. Nature. 1996;383:728–31.

    Article  CAS  PubMed  Google Scholar 

  46. Lehmann JM, Kliewer SA, Moore LB, Smith-Oliver TA, Oliver BB, Su JL, et al. Activation of the nuclear receptor LXR by oxysterols defines a new hormone response pathway. J Biol Chem. 1997;272:3137–40.

    Article  CAS  PubMed  Google Scholar 

  47. Theofilopoulos S, Arenas E. Liver X receptors and cholesterol metabolism: role in ventral midbrain development and neurodegeneration. F1000prime Rep. 2015;7:37.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. Nelson ER, Wardell SE, Jasper JS, Park S, Suchindran S, Howe MK, et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology. Science. 2013;342:1094–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  49. Fu X, Menke JG, Chen YL, Zhou GC, MacNaul KL, Wright SD, et al. 27-hydroxycholesterol is an endogenous ligand for liver X receptor in cholesterol-loaded cells. J Biol Chem. 2001;276:38378–87.

    Article  CAS  PubMed  Google Scholar 

  50. Trousson A, Bernard S, Petit PX, Liere P, Pianos A, El Hadri K, et al. 25-hydroxycholesterol provokes oligodendrocyte cell line apoptosis and stimulates the secreted phospholipase A2 type IIA via LXR beta and PXR. J Neurochem. 2009;109:945–58.

    Article  CAS  PubMed  Google Scholar 

  51. Bai Q, Xu L, Kakiyama G, Runge-Morris MA, Hylemon PB, Yin L, et al. Sulfation of 25-hydroxycholesterol by SULT2B1b decreases cellular lipids via the LXR/SREBP-1c signaling pathway in human aortic endothelial cells. Atherosclerosis. 2011;214:350–6.

    Article  CAS  PubMed  Google Scholar 

  52. Adams CM, Reitz J, De Brabander JK, Feramisco JD, Li L, Brown MS, et al. Cholesterol and 25-hydroxycholesterol inhibit activation of SREBPs by different mechanisms, both involving SCAP and insigs. J Biol Chem. 2004;279:52772–80.

    Article  CAS  PubMed  Google Scholar 

  53. Bauman DR, Bitmansour AD, McDonald JG, Thompson BM, Liang GS, Russell DW. 25-Hydroxycholesterol secreted by macrophages in response to Toll-like receptor activation suppresses immunoglobulin A production. Proc Natl Acad Sci U S A. 2009;106:16764–9.

    Article  PubMed  PubMed Central  Google Scholar 

  54. Kim WK, Meliton V, Tetradis S, Weinmaster G, Hahn TJ, Carlson M, et al. Osteogenic oxysterol, 20(S)-hydroxycholesterol, induces notch target gene expression in bone marrow stromal cells. J Bone Miner Res Off J Am Soc Bone Miner Res. 2010;25:782–95.

    Article  CAS  Google Scholar 

  55. Lin YY, Welch M, Lieberman S. The detection of 20(S)-hydroxycholesterol in extracts of rat brains and human placenta by a gas chromatograph/mass spectrometry technique. J Steroid Biochem. 2003;85:57–61.

    Article  CAS  Google Scholar 

  56. Antica M, Kusic B, Hranilovic D, Dietz AB, Vuk-Pavlovic S. Cloning the cDNA for murine U2 snRNP-A’ gene and its differential expression in lymphocyte development. Immunol Lett. 2002;82:217–23.

    Article  CAS  PubMed  Google Scholar 

  57. Song C, Hiipakka RA, Liao SS. Selective activation of liver X receptor alpha by 6 alpha-hydroxy bile acids and analogs. Steroids. 2000;65:423–7.

    Article  CAS  PubMed  Google Scholar 

  58. Berrodin TJ, Shen Q, Quinet EM, Yudt MR, Freedman LP, Nagpal S. Identification of 5 alpha,6 alpha-Epoxycholesterol as a novel modulator of liver X receptor activity. Mol Pharmacol. 2010;78:1046–58.

    Article  CAS  PubMed  Google Scholar 

  59. Xu ZM, Hua N, Godber JS. Antioxidant activity of tocopherols, tocotrienols, and gamma-oryzanol components from rice bran against cholesterol oxidation accelerated by 2,2 ‘-azobis(2-methylpropionamidine) dihydrochloride. J Agric Food Chem. 2001;49:2077–81.

    Article  CAS  PubMed  Google Scholar 

  60. Kaneko T, Kanno C, Ichikawa-Tomikawa N, Kashiwagi K, Yaginuma N, Ohkoshi C, et al. Liver X receptor reduces proliferation of human oral cancer cells by promoting cholesterol efflux via up-regulation of ABCA1 expression. Oncotarget. 2015;6:33345–57.

    Article  PubMed  PubMed Central  Google Scholar 

  61. Yeh YS, Goto T, Takahashi N, Egawa K, Takahashi H, Jheng HF, et al. Geranylgeranyl pyrophosphate performs as an endogenous regulator of adipocyte function via suppressing the LXR pathway. Biochem Bioph Res Co. 2016;478:1317–22.

    Article  CAS  Google Scholar 

  62. Han D, Li X, Li S, Su T, Fan L, Fan WS, et al. Reduced silent information regulator 1 signaling exacerbates sepsis-induced myocardial injury and mitigates the protective effect of a liver X receptor agonist. Free Radical Bio Med. 2017;113:291–303.

    Article  CAS  Google Scholar 

  63. Wongwan T, Kittayaruksakul S, Asavapanumas N, Chatsudthipong V, Soodvilai S. Activation of liver X receptor inhibits OCT2-mediated organic cation transport in renal proximal tubular cells. Pflug Arch Eur J Phy. 2017;469:1471–81.

    Article  CAS  Google Scholar 

  64. Gong YB, Yang YF, Wu Q, Gao G, Liu Y, Xiong YY, et al. Activation of LXR alpha improves cardiac remodeling induced by pulmonary artery hypertension in rats. Sci Rep-Uk. 2017:7.

  65. Chen QJ, Shi Y, Shi JF, Yuan ZH, Ma JY, Fang SR, et al. Liver X receptors agonist T0901317 downregulates matrix metalloproteinase-9 expression in non-small-cell lung cancer by repressing nuclear factor-kappa B. Anti-Cancer Drug. 2017;28:952–8.

    Article  CAS  Google Scholar 

  66. Fu Y, Tian Y, Wei Z, Liu H, Song X, Liu W, et al. Liver X receptor agonist prevents LPS-induced mastitis in mice. Int Immunopharmacol. 2014;22:379–83.

    Article  CAS  PubMed  Google Scholar 

  67. Ma ZQ, Deng C, Hu W, Zhou J, Fan CX, Di SY, et al. Liver X receptors and their agonists: targeting for cholesterol homeostasis and cardiovascular diseases. Curr Issues Mol Biol. 2017;22:41–63.

    Article  PubMed  Google Scholar 

  68. Cheng O, Ostrowski RP, Liu W, Zhang JH. Activation of liver X receptor reduces global ischemic brain injury by reduction of nuclear factor-kappa B. Neuroscience. 2010;166:1101–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  69. Zhang R, Liu ZG, Li YC, Wu B. LXR agonist regulates the proliferation and apoptosis of human T-Cell acute lymphoblastic leukemia cells via the SOCS3 pathway. Int J Biochem Cell B. 2016;78:180–5.

    Article  CAS  Google Scholar 

  70. Tontonoz P, Mangelsdorf DJ. Liver X receptor signaling pathways in cardiovascular disease. Mol Endocrinol. 2003;17:985–93.

    Article  CAS  PubMed  Google Scholar 

  71. Lund EG, Menke JG, Sparrow CP. Liver X receptor agonists as potential therapeutic agents for dyslipidemia and atherosclerosis. Arterioscl Throm Vas. 2003;23:1169–77.

    Article  CAS  Google Scholar 

  72. Steffensen KR, Gustafsson JA. Putative metabolic effects of the liver x receptor (LXR). Diabetes. 2004;53:S36–42.

    Article  CAS  PubMed  Google Scholar 

  73. Yasuda T, Grillot D, Billheimer JT, Briand F, Delerive P, Huet S, et al. Tissue-specific liver X receptor activation promotes macrophage reverse cholesterol transport in vivo. Arterioscl Throm Vas. 2010;30:781–U313.

    Article  CAS  Google Scholar 

  74. Bremner P, Heinrich M. Natural products as targeted modulators of the nuclear factor-kappa B pathway. J Pharm Pharmacol. 2002;54:453–72.

    Article  CAS  PubMed  Google Scholar 

  75. Traves PG, Hortelano S, Zeini M, Chao TH, Lam T, Neuteboom ST, et al. Selective activation of liver X receptors by acanthoic acid-related diterpenes. Mol Pharmacol. 2007;71:1545–53.

    Article  CAS  PubMed  Google Scholar 

  76. Cuadrado I, Fernandez-Velasco M, Bosca L. de las Heras B. Labdane diterpenes protect against anoxia/reperfusion injury in cardiomyocytes: involvement of AKT activation. Cell Death Dis. 2011;2

  77. Hoang MH, Jia Y, Jun HJ, Lee JH, Lee BY, Lee SJ. Fucosterol is a selective liver X receptor modulator that regulates the expression of key genes in cholesterol homeostasis in macrophages, hepatocytes, and Intestinal cells. J Agric Food Chem. 2012;60:11567–75.

    Article  CAS  PubMed  Google Scholar 

  78. Jiang HY, Li J, Chen AY, Li YG, Xia M, Guo P, et al. Fucosterol exhibits selective antitumor anticancer activity against HeLa human cervical cell line by inducing mitochondrial mediated apoptosis, cell cycle migration inhibition and downregulation of m-TOR/PI3K/Akt signalling pathway. Oncol Lett. 2018;15:3458–63.

    PubMed  PubMed Central  Google Scholar 

  79. Jia Y, Hoang MH, Jun HJ, Lee JH, Lee SJ. Cyanidin, a natural flavonoid, is an agonistic ligand for liver X receptor alpha and beta and reduces cellular lipid accumulation in macrophages and hepatocytes. Bioorg Med Chem Lett. 2013;23:4185–90.

    Article  CAS  PubMed  Google Scholar 

  80. Suantawee T, Elazab ST, Hsu WH, Yao SM, Cheng H, Adisakwattana S. Cyanidin stimulates insulin secretion and pancreatic beta-cell gene expression through activation of L-type voltage-dependent Ca2+ channels. Nutrients. 2017;9

  81. Jung CG, Horike H, Cha BY, Uhm KO, Yamauchi R, Yamaguchi T, et al. Honokiol increases ABCA1 expression level by activating retinoid X receptor beta. Biol Pharm Bull. 2010;33:1105–11.

    Article  CAS  PubMed  Google Scholar 

  82. Huang JS, Yao CJ, Chuang SE, Yeh CT, Lee LM, Chen RM, et al. Honokiol inhibits sphere formation and xenograft growth of oral cancer side population cells accompanied with JAK/STAT signaling pathway suppression and apoptosis induction. Bmc Cancer. 2016;16

  83. Lin HR. Paeoniflorin acts as a liver X receptor agonist. J Asian Nat Prod Res. 2013;15:35–45.

    Article  CAS  PubMed  Google Scholar 

  84. Zheng YB, Xiao GC, Tong SL, Ding Y, Wang QS, Li SB, et al. Paeoniflorin inhibits human gastric carcinoma cell proliferation through up-regulation of microRNA-124 and suppression of PI3K/Akt and STAT3 signaling. World J Gastroenterol. 2015;21:7197–207.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  85. Jun HJ, Hoang MH, Lee JW, Yaoyao J, Lee JH, Lee DH, et al. Iristectorigenin B isolated from Belamcanda chinensis is a liver X receptor modulator that increases ABCA1 and ABCG1 expression in macrophage RAW 264.7 cells. Biotechnol Lett. 2012;34:2213–21.

    Article  CAS  PubMed  Google Scholar 

  86. Singh SB, Ondeyka JG, Liu WG, Chen S, Chen TS, Li XH, et al. Discovery and development of dimeric podocarpic acid leads as potent agonists of liver X receptor with HDL cholesterol raising activity in mice and hamsters. Bioorg Med Chem Lett. 2005;15:2824–8.

    Article  CAS  PubMed  Google Scholar 

  87. Liu B, He ZQ, Wang JJ, Xin ZY, Wang JX, Li F, et al. Taraxasterol inhibits LPS-induced inflammatory response in BV2 zmicroglia cells by activating LXR alpha. Front Pharmacol. 2018:9.

  88. Bao T, Ke Y, Wang Y, Wang W, Li Y, Wang Y, et al. Taraxasterol suppresses the growth of human liver cancer by upregulating Hint1 expression. J Mol Med. 2018;96:661–72.

    Article  CAS  PubMed  Google Scholar 

  89. Fu YH, Xin ZY, Liu B, Wang JX, Wang JJ, Zhang X, et al. Platycodin D inhibits inflammatory response in LPS-stimulated primary rat microglia cells through activating LXR alpha-ABCA1 signaling pathway. Front Immunol. 2018:8.

  90. Kwon J, Lee H, Kim N, Lee JH, Woo MH, Kim J, et al. Effect of processing method on platycodin D content in Platycodon grandiflorum roots. Arch Pharm Res. 2017;40:1087–93.

    Article  CAS  PubMed  Google Scholar 

  91. Wei Z, Wang J, Shi M, Liu W, Yang Z, Fu Y. Saikosaponin a inhibits LPS-induced inflammatory response by inducing liver X receptor alpha activation in primary mouse macrophages. Oncotarget. 2016;7:48995–9007.

    PubMed  PubMed Central  Google Scholar 

  92. Wang N, Che D, Zhang T, Liu R, Cao J, Wang J, et al. Saikosaponin A inhibits compound 48/80-induced pseudo-allergy via the Mrgprx2 pathway in vitro and in vivo. Biochem Pharmacol. 2018;148:147–54.

    Article  CAS  PubMed  Google Scholar 

  93. Levison LJ, Miller-Cushon EK, Tucker AL, Bergeron R, Leslie KE, Barkema HW, et al. Incidence rate of pathogen-specific clinical mastitis on conventional and organic Canadian dairy farms. J Dairy Sci. 2016;99:1341–50.

    Article  CAS  PubMed  Google Scholar 

  94. Riekerink RGMO, Barkema HW, Kelton DF, Scholl DT. Incidence rate of clinical mastitis on Canadian dairy farms. J Dairy Sci. 2008;91:1366–77.

    Article  CAS  Google Scholar 

  95. Waage S, Mork T, Roros A, Aasland D, Hunshamar A, Odegaard SA. Bacteria associated with clinical mastitis in dairy heifers. J Dairy Sci. 1999;82:712–9.

    Article  CAS  PubMed  Google Scholar 

  96. Zhao YT, Gorshkova IA, Berdyshev E, He DH, Fu PF, Ma WL, et al. Protection of LPS-induced murine acute lung injury by sphingosine-1-phosphate lyase suppression. Am J Resp Cell Mol. 2011;45:426–35.

    Article  CAS  Google Scholar 

  97. Elazar S, Gonen E, Livneh-Kol A, Rosenshine I, Shpigel NY. Neutrophil recruitment in endotoxin-induced murine mastitis is strictly dependent on mammary alveolar macrophages. Vet Res. 2010;41

  98. Gu BB, Miao JF, Fa YM, Lu JY, Zou SX. Retinoic acid attenuates lipopolysaccharide-induced inflammatory responses by suppressing TLR4/NF-kappa B expression in rat mammary tissue. Int Immunopharmacol. 2010;10:799–805.

    Article  CAS  PubMed  Google Scholar 

  99. Ammari FF, Yaghan RJ, Omari AKH. Periductal mastitis - clinical characteristics and outcome. Saudi Med J. 2002;23:819–22.

    PubMed  Google Scholar 

  100. Shpigel NY, Levin D, Winkler M, Saran A, Ziv G, Bottner A. Efficacy of cefquinome for treatment of cows with mastitis experimentally induced using Escherichia coli. J Dairy Sci. 1997;80:318–23.

    Article  CAS  PubMed  Google Scholar 

  101. Man SM, Karki R, Kanneganti TD. Molecular mechanisms and functions of pyroptosis, inflammatory caspases and inflammasomes in infectious diseases. Immunol Rev. 2017;277:61–75.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  102. Lamkanfi M, Dixit VM. Mechanisms and functions of inflammasomes. Cell. 2014;157:1013–22.

    Article  CAS  PubMed  Google Scholar 

  103. Palm NW, Medzhitov R. Pattern recognition receptors and control of adaptive immunity. Immunol Rev. 2009;227:221–33.

    Article  CAS  PubMed  Google Scholar 

  104. Nosratabadi R, Alavian SM, Zare-Bidaki M, Shahrokhi VM, Arababadi MK. Innate immunity related pathogen recognition receptors and chronic hepatitis B infection. Mol Immunol. 2017;90:64–73.

    Article  CAS  PubMed  Google Scholar 

  105. Genster N, Ma YJ, Munthe-Fog L, Garred P. The innate pathogen recognition molecule ficolin-1 exhibit differential binding to leukocyte subsets, providing a novel link between innate and adaptive immunity. Mol Immunol. 2013;56:259.

    Article  Google Scholar 

  106. Genster N, Ma YJ, Munthe-Fog L, Garred P. The innate pathogen recognition molecule ficolin-1 exhibit differential binding to leukocyte subsets, providing a novel link between innate and adaptive immunity. Scand J Immunol. 2013;77:263.

    Google Scholar 

  107. Sochocka M. Recognition of pathogens by innate immunity. Postepy higieny i medycyny doswiadczalnej. 2008;62:676–87.

    PubMed  Google Scholar 

  108. Park BS, Lee JO. Recognition of lipopolysaccharide pattern by TLR4 complexes. Exp Mol Med. 2013;45

  109. Ibeagha-Awemu EM, Lee JW, Ibeagha AE, Bannerman DD, Paape MJ, Zhao X. Bacterial lipopolysaccharide induces increased expression of toll-like receptor (TLR) 4 and downstream TLR signaling molecules in bovine mammary epithelial cells. Vet Res. 2008;39

  110. Porcherie A, Cunha P, Trotereau A, Roussel P, Gilbert FB, Rainard P, et al. Repertoire of Escherichia coli agonists sensed by innate immunity receptors of the bovine udder and mammary epithelial cells. Vet Res. 2012;43

  111. De Schepper S, De Ketelaere A, Bannerman DD, Paape MJ, Peelman L, Burvenich C. The toll-like receptor-4 (TLR-4) pathway and its possible role in the pathogenesis of Escherichia coli mastitis in dairy cattle. Vet Res. 2008;39

  112. Lu YC, Yeh WC, Ohashi PS. LPS/TLR4 signal transduction pathway. Cytokine. 2008;42:145–51.

    Article  CAS  PubMed  Google Scholar 

  113. Kawai T, Akira S. Toll-like receptors and their crosstalk with other innate receptors in infection and immunity. Immunity. 2011;34:637–50.

    Article  CAS  Google Scholar 

  114. Gunther J, Petzl W, Bauer I, Ponsuksili S, Zerbe H, Schuberth HJ, et al. Differentiating Staphylococcus aureus from Escherichia coli mastitis: S. aureus triggers unbalanced immune-dampening and host cell invasion immediately after udder infection. Sci Rep-Uk. 2017;7

  115. Triantafilou M, Miyake K, Golenbock DT, Triantafilou K. Mediators of innate immune recognition of bacteria concentrate in lipid rafts and facilitate lipopolysaccharide-induced cell activation. J Cell Sci. 2002;115:2603–11.

    CAS  PubMed  Google Scholar 

  116. Cuschieri J, Billigren J, Maier RV. Endotoxin tolerance attenuates LPS-induced TLR4 mobilization to lipid rafts: a condition reversed by PKC activation. J Leukocyte Biol. 2006;80:1289–97.

    Article  CAS  PubMed  Google Scholar 

  117. Tsuda K, Furuta N, Inaba H, Kawai S, Hanada K, Yoshimori T, et al. Functional analysis of alpha 5 beta 1 integrin and lipid rafts in invasion of epithelial cells by porphyromonas gingivalis using fluorescent beads coated with bacterial membrane vesicles. Cell Struct Funct. 2008;33:123–32.

    Article  CAS  PubMed  Google Scholar 

  118. Maselli A, Pierdominici M, Vitale C, Ortona E. Membrane lipid rafts and estrogenic signalling: a functional role in the modulation of cell homeostasis. Apoptosis. 2015;20:671–8.

    Article  CAS  PubMed  Google Scholar 

  119. Papavlassopoulos M, Stamme C, Thon L, Adam D, Hillemann D, Seydel U, et al. MaxiK blockade selectively inhibits the lipopolysaccharide-induced I kappa B-alpha/NF-kappa B signaling pathway in macrophages. J Immunol. 2006;177:4086–93.

    Article  CAS  PubMed  Google Scholar 

  120. Lu DY, Chen HC, Yang MS, Hsu YM, Lin HJ, Tang CH, et al. Ceramide and toll-like receptor 4 are mobilized into membrane rafts in Response to helicobacter pylori infection in gastric epithelial cells. Infect Immun. 2012;80:1823–33.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  121. Powers KA, Szaszi K, Khadaroo RG, Tawadros PS, Marshall JC, Kapus A, et al. Oxidative stress generated by hemorrhagic shock recruits Toll-like receptor 4 to the plasma membrane in macrophages. J Exp Med. 2006;203:1951–61.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  122. Fu YH, Zhou ES, Wei ZK, Liang DJ, Wang W, Wang TC, et al. Glycyrrhizin inhibits the inflammatory response in mouse mammary epithelial cells and a mouse mastitis model. Febs J. 2014;281:2543–57.

    Article  CAS  PubMed  Google Scholar 

  123. Fu YH, Wei ZK, Zhou ES, Zhang NS, Yang ZT. Cyanidin-3-O-beta-glucoside inhibits lipopolysaccharide-induced inflammatory response in mouse mastitis model. J Lipid Res. 2014;55:1111–9.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. Sohi G, Revesz A, Arany E, Hardy DB. The liver X receptor mediates the impaired cholesterol metabolism exhibited in the offspring of maternal protein restricted rats. Reprod Sci. 2011;18:220a-a.

    Google Scholar 

  125. Giorelli M, Livrea R, Trojano M. Cholesterol metabolism reveals liver X receptor beta as a novel potential therapeutic target in multiple sclerosis. Mult Scler. 2005;11:S165-S.

    Google Scholar 

  126. Zhao CY, Dahlman-Wright K. Liver X receptor in cholesterol metabolism. J Endocrinol. 2010;204:233–40.

    Article  CAS  PubMed  Google Scholar 

  127. Repa JJ, Liang GS, Ou JF, Bashmakov Y, Lobaccaro JMA, Shimomura I, et al. Regulation of mouse sterol regulatory element-binding protein-1c gene (SREBP-1c) by oxysterol receptors, LXR alpha and LXR beta. Genes Dev. 2000;14:2819–30.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  128. Basso F, Freeman L, Knapper CL, Remaley A, Stonik J, Neufeld EB, et al. Role of the hepatic ABCA1 transporter in modulating intrahepatic cholesterol and plasma HDL cholesterol concentrations. J Lipid Res. 2003;44:296–302.

    Article  CAS  PubMed  Google Scholar 

  129. Christiansen-Weber TA, Voland JR, Wu Y, Ngo K, Roland BL, Nguyen S, et al. Functional loss of ABCA1 in mice causes severe placental malformation, aberrant lipid distribution, and kidney glomerulonephritis as well as high-density lipoprotein cholesterol deficiency. Am J Pathol. 2000;157:1017–29.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  130. McNeish J, Aiello RJ, Guyot D, Turi T, Gabel C, Aldinger C, et al. High density lipoprotein deficiency and foam cell accumulation in mice with targeted disruption of ATP-binding cassette transporter-1. Proc Natl Acad Sci U S A. 2000;97:4245–50.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  131. Zhu X, Lee JY, Timmins JM, Brown JM, Boudyguina E, Mulya A, et al. Increased cellular free cholesterol in macrophage-specific Abca1 knock-out mice enhances pro-inflammatory response of macrophages. Journal of Biological Chemistry. 2008;283:22930–41.

    Article  CAS  PubMed  Google Scholar 

  132. Kennedy MA, Venkateswaran A, Tarr PT, Xenarios I, Kudoh J, Shimizu N, et al. Characterization of the human ABCG1 gene. Liver X receptor activates an internal promoter that produces a novel transcript encoding an alternative form of the protein (vol 276, pg 39,438, 2001). J Biol Chem. 2002;277:17375.

    CAS  Google Scholar 

  133. Yvan-Charvet L, Wang N, Tall AR. Role of HDL, ABCA1, and ABCG1 transporters in cholesterol efflux and immune responses. Arterioscl Throm Vas. 2010;30:139–43.

    Article  CAS  Google Scholar 

  134. Noghero A, Perino A, Seano G, Saglio E, Lo Sasso G, Veglio F, et al. Liver X receptor activation reduces angiogenesis by impairing lipid raft localization and signaling of vascular endothelial growth factor receptor-2. Arterioscl Throm Vas. 2012;32:2280.

    Article  CAS  Google Scholar 

  135. Yvan-Charvet L, Pagler T, Gautier EL, Avagyan S, Siry RL, Han S, et al. ATP-binding cassette transporters and HDL suppress hematopoietic stem cell proliferation. Science. 2010;328:1689–93.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  136. Wang YY, Dahle MK, Agren J, Myhre AE, Reinholt FP, Foster SJ, et al. Activation of the liver X receptor protects against hepatic injury in endotoxemia by suppressing Kupffer cell activation. Shock. 2006;25:141–6.

    Article  CAS  PubMed  Google Scholar 

  137. Walcher D, Kummel A, Kehrle B, Bach H, Grub M, Durst R, et al. LXR activation reduces proinflammatory cytokine expression in human CD4-positive lymphocytes. Arterioscl Throm Vas. 2006;26:1022–8.

    Article  CAS  Google Scholar 

  138. Ito A, Hong C, Rong X, Zhu XW, Tarling EJ, Hedde PN, et al. LXRs link metabolism to inflammation through Abca1-dependent regulation of membrane composition and TLR signaling. Elife. 2015;4

  139. Fu YH, Hu XY, Cao YG, Zhang ZC, Zhang NS. Saikosaponin a inhibits lipopolysaccharide-oxidative stress and inflammation in Human umbilical vein endothelial cells via preventing TLR4 translocation into lipid rafts. Free Radical Bio Med. 2015;89:777–85.

    Article  CAS  Google Scholar 

  140. Salama AAK, Caja G, Hamzaoui S, Badaoui B, Castro-Costa A, Facanha DAE, et al. Different levels of response to heat stress in dairy goats. Small Ruminant Res. 2014;121:73–9.

    Article  Google Scholar 

  141. Wang JJ, Xiao C, Wei ZK, Wang YN, Zhang X, Fu YH. Activation of liver X receptors inhibit LPS-induced inflammatory response in primary bovine mammary epithelial cells. Vet Immunol Immunopathol. 2018;197:87–92.

    Article  CAS  PubMed  Google Scholar 

  142. Wang Y, Zhang X, Wei Z, Wang J, Zhang Y, Shi M, et al. Platycodin D suppressed LPS-induced inflammatory response by activating LXRalpha in LPS-stimulated primary bovine mammary epithelial cells. Eur J Pharmacol. 2017;814:138–43.

    Article  CAS  PubMed  Google Scholar 

  143. Jensen RG. The composition of bovine milk lipids: January 1995 to December 2000. J Dairy Sci. 2002;85:295–350.

    Article  CAS  PubMed  Google Scholar 

  144. Theolier J, Fliss I, Jean J, Hammami R. Antimicrobial peptides of dairy proteins: from fundamental to applications. Food Rev Int. 2014;30:134–54.

    Article  CAS  Google Scholar 

  145. Ravenel MP. Fundamentals of dairy science. Am J Public Health N. 1935;25:658–9.

    Article  Google Scholar 

  146. Bauman DE, Griinari JM. Nutritional regulation of milk fat synthesis. Annu Rev Nutr. 2003;23:203–27.

    Article  CAS  PubMed  Google Scholar 

  147. Lin XZ, Luo J, Zhang LP, Wang W, Shi HB, Zhu JJ. miR-27a suppresses triglyceride accumulation and affects gene mRNA expression associated with fat metabolism in dairy goat mammary gland epithelial cells. Gene. 2013;521:15–23.

    Article  CAS  PubMed  Google Scholar 

  148. Lock AL, Bauman DE. Modifying milk fat composition of dairy cows to enhance fatty acids beneficial to human health. Lipids. 2004;39:1197–206.

    Article  CAS  PubMed  Google Scholar 

  149. Spitsberg VL. Bovine milk fat globule membrane as a potential nutraceutical. J Dairy Sci. 2005;88:2289–94.

    Article  CAS  PubMed  Google Scholar 

  150. Kugimiya A, Takagi J, Uesugi M. Role of LXRs in control of lipogenesis. Tanpakushitsu kakusan koso Protein, nucleic acid enzyme. 2007;52:1814–5.

    Google Scholar 

  151. Schultz JR, Tu H, Luk A, Repa JJ, Medina JC, Li L, et al. Role of LXRs in control of lipogenesis. Genes Dev. 2000;14:2831–8.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  152. Willy PJ, Umesono K, Ong ES, Evans RM, Heyman RA, Mangelsdorf DJLXR. a nuclear receptor that defines a distinct retinoid response pathway. Genes Dev. 1995;9:1033–45.

    Article  CAS  PubMed  Google Scholar 

  153. McFadden JW, Corl BA. Activation of liver X receptor (LXR) enhances de novo fatty acid synthesis in bovine mammary epithelial cells. J Dairy Sci. 2010;93:4651–8.

    Article  CAS  PubMed  Google Scholar 

  154. Peet DJ, Turley SD, Ma W, Janowski BA, Lobaccaro JM, Hammer RE, et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXR alpha. Cell. 1998;93:693–704.

    Article  CAS  PubMed  Google Scholar 

  155. Li J, Luo J, Zhu JJ, Sun YT, Yao DW, Shi HB, et al. Regulation of the fatty acid synthase promoter by liver X receptor alpha through direct and indirect mechanisms in goat mammary epithelial cells. Comp Biochem Phys B. 2015;184:44–51.

    Article  CAS  Google Scholar 

  156. Mani O, Korner M, Sorensen MT, Sejrsen K, Wotzkow C, Ontsouka CE, et al. Expression, localization, and functional model of cholesterol transporters in lactating and nonlactating mammary tissues of murine, bovine, and human origin. Am J Physiol-Reg I. 2010;299:R642–R54.

    CAS  Google Scholar 

  157. Oppi-Williams C, Suagee JK, Corl BA. Regulation of lipid synthesis by liver X receptor alpha and sterol regulatory element-binding protein 1 in mammary epithelial cells. J Dairy Sci. 2013;96:112–21.

    Article  CAS  PubMed  Google Scholar 

  158. Ndisang JF. Cross-talk between heme oxygenase and peroxisome proliferator-activated receptors in the regulation of physiological functions. Front Biosci-Landmrk. 2014;19:916–35.

    Article  Google Scholar 

  159. Ide T, Shimano H, Yoshikawa T, Yahagi N, Amemiya-Kudo M, Matsuzaka T, et al. Cross-talk between peroxisome proliferator-activated receptor (PPAR) alpha and liver X receptor (LXR) in nutritional regulation of fatty acid metabolism. II. LXRs suppress lipid degradation gene promoters through inhibition of PPAR signaling. Mol Endocrinol. 2003;17:1255–67.

    Article  CAS  PubMed  Google Scholar 

  160. Willson TM, Brown PJ, Sternbach DD, Henke BR. The PPARs: From orphan receptors to drug discovery. J Med Chem. 2000;43:527–50.

    Article  CAS  PubMed  Google Scholar 

  161. Anderson SM, Rudolph MC, McManaman JL, Neville MC. Key stages in mammary gland development. Secretory activation in the mammary gland: it’s not just about milk protein synthesis! Breast Cancer Res: BCR. 2007;9:204.

    Article  CAS  PubMed  Google Scholar 

  162. Bionaz M, Loor JJ. Gene networks driving bovine milk fat synthesis during the lactation cycle. BMC Genomics. 2008;9:366.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  163. Sharma R, Torka P. Peroxisome proliferator-activated receptor-delta induces insulin-induced gene-1 and suppresses hepatic lipogenesis in obese diabetic mice. Hepatology. 2008;48:2085. author reply −6

    Article  PubMed  Google Scholar 

  164. Qin X, Xie X, Fan Y, Tian J, Guan Y, Wang X, et al. Peroxisome proliferator-activated receptor-delta induces insulin-induced gene-1 and suppresses hepatic lipogenesis in obese diabetic mice. Hepatology. 2008;48:432–41.

    Article  CAS  PubMed  Google Scholar 

  165. Kast-Woelbern HR, Dana SL, Cesario RM, Sun L, de Grandpre LY, Brooks ME, et al. Rosiglitazone induction of Insig-1 in white adipose tissue reveals a novel interplay of peroxisome proliferator-activated receptor gamma and sterol regulatory element-binding protein in the regulation of adipogenesis. J Biol Chem. 2004;279:23908–15.

    Article  CAS  PubMed  Google Scholar 

  166. Moyes KM, Drackley JK, Morin DE, Bionaz M, Rodriguez-Zas SL, Everts RE, et al. Gene network and pathway analysis of bovine mammary tissue challenged with Streptococcus uberis reveals induction of cell proliferation and inhibition of PPAR gamma signaling as potential mechanism for the negative relationships between immune response and lipid metabolism. BMC Genomics. 2009;10

  167. Liu LL, Lin Y, Liu LX, Wang LN, Bian YJ, Gao XJ, et al. Regulation of peroxisome proliferator-activated receptor gamma on milk fat synthesis in dairy cow mammary epithelial cells. In Vitro Cell Dev-An. 2016;52:1044–59.

    Article  CAS  Google Scholar 

  168. Kadegowda AK, Khan MJ, Piperova LS, Teter BB, Rodriguez-Zas SL, Erdman RA, et al. Trans-10, cis 12-conjugated linoleic acid-induced milk fat depression is associated with inhibition of ppargamma signaling and inflammation in murine mammary tissue. J Lipids. 2013;2013:890343.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

This work was supported by a grant from the National Natural Science Foundation of China (Nos. 31602122) and China Postdoctoral Science Foundation funded project (2016 M600233).

Author information

Authors and Affiliations

  1. Department of Clinical Veterinary Medicine, College of Veterinary Medicine, Jilin University, Changchun, Jilin Province, 130062, People’s Republic of China

    Xiaoyu Hu, Naisheng Zhang & Yunhe Fu

Authors
  1. Xiaoyu Hu
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Naisheng Zhang
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Yunhe Fu
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding authors

Correspondence to Naisheng Zhang or Yunhe Fu.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Hu, X., Zhang, N. & Fu, Y. Role of Liver X Receptor in Mastitis Therapy and Regulation of Milk Fat Synthesis. J Mammary Gland Biol Neoplasia 24, 73–83 (2019). https://doi.org/10.1007/s10911-018-9403-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10911-018-9403-5

Keywords

Search

Navigation