<?xml version="1.0" encoding="UTF-8"?>
<!DOCTYPE root>
<article xmlns:mml="http://www.w3.org/1998/Math/MathML" xmlns:xlink="http://www.w3.org/1999/xlink" xmlns:xsi="http://www.w3.org/2001/XMLSchema-instance" xmlns:ali="http://www.niso.org/schemas/ali/1.0/" article-type="research-article" dtd-version="1.2" xml:lang="en"><front><journal-meta><journal-id journal-id-type="publisher-id">Medical academic journal</journal-id><journal-title-group><journal-title xml:lang="en">Medical academic journal</journal-title><trans-title-group xml:lang="ru"><trans-title>Медицинский академический журнал</trans-title></trans-title-group></journal-title-group><issn publication-format="print">1608-4101</issn><issn publication-format="electronic">2687-1378</issn><publisher><publisher-name xml:lang="en">Eco-Vector</publisher-name></publisher></journal-meta><article-meta><article-id pub-id-type="publisher-id">62892</article-id><article-id pub-id-type="doi">10.17816/MAJ62892</article-id><article-categories><subj-group subj-group-type="toc-heading" xml:lang="en"><subject>Original study articles</subject></subj-group><subj-group subj-group-type="toc-heading" xml:lang="ru"><subject>Оригинальные исследования</subject></subj-group><subj-group subj-group-type="article-type"><subject>Research Article</subject></subj-group></article-categories><title-group><article-title xml:lang="en">Mechanisms of the influence of adiponectin on apolipoproteins A-1 and B production by human hepatocytes</article-title><trans-title-group xml:lang="ru"><trans-title>Механизмы влияния адипонектина на продукцию аполипопротеинов А-1 и B гепатоцитами человека</trans-title></trans-title-group></title-group><contrib-group><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0002-5321-8834</contrib-id><contrib-id contrib-id-type="spin">9303-9445</contrib-id><name-alternatives><name xml:lang="en"><surname>Tanyanskiy</surname><given-names>Dmitriy A.</given-names></name><name xml:lang="ru"><surname>Танянский</surname><given-names>Дмитрий Андреевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD (Medicine), Head of Laboratory of Lipoproteins, Department of Biochemistry</p></bio><bio xml:lang="ru"><p>канд. мед. наук, заведующий лабораторией липопротеинов им. акад. РАМН А.Н. Климова отдела биохимии</p></bio><email>dmitry.athero@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0001-5147-4749</contrib-id><contrib-id contrib-id-type="spin">1625-0496</contrib-id><name-alternatives><name xml:lang="en"><surname>Dizhe</surname><given-names>Ella B.</given-names></name><name xml:lang="ru"><surname>Диже</surname><given-names>Элла Борисовна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD (Biology), Leading Researcher, Department of Biochemistry</p></bio><bio xml:lang="ru"><p>канд. биол. наук, ведущий научный сотрудник отдела биохимии</p></bio><email>dizhe@iem.sp.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><name-alternatives><name xml:lang="en"><surname>Oleinikova</surname><given-names>Galina N.</given-names></name><name xml:lang="ru"><surname>Олейникова</surname><given-names>Галина Николаевна</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>Research Assistant, Department of Biochemistry</p></bio><bio xml:lang="ru"><p>лаборант-исследователь отдела биохимии</p></bio><email>galina@iem.sp.ru</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="spin">5428-6800</contrib-id><name-alternatives><name xml:lang="en"><surname>Shavva</surname><given-names>Vladimir S.</given-names></name><name xml:lang="ru"><surname>Шавва</surname><given-names>Владимир Станиславович</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD (Biology), Senior Researcher, Department of Biochemistry</p></bio><bio xml:lang="ru"><p>канд. биол. наук, старший научный сотрудник отдела биохимии</p></bio><email>vssreinard.fox@gmail.com</email><xref ref-type="aff" rid="aff1"/></contrib><contrib contrib-type="author"><contrib-id contrib-id-type="orcid">https://orcid.org/0000-0003-1613-0654</contrib-id><contrib-id contrib-id-type="spin">7496-1449</contrib-id><name-alternatives><name xml:lang="en"><surname>Denisenko</surname><given-names>Aleksandr D.</given-names></name><name xml:lang="ru"><surname>Денисенко</surname><given-names>Александр Дорофеевич</given-names></name></name-alternatives><address><country country="RU">Russian Federation</country></address><bio xml:lang="en"><p>MD, PhD, DSc (Medicine), Professor, Head of Department of Biochemistry</p></bio><bio xml:lang="ru"><p>д-р мед. наук, профессор, заведующий отделом биохимии</p></bio><email>add@iem.sp.ru</email><xref ref-type="aff" rid="aff1"/></contrib></contrib-group><aff-alternatives id="aff1"><aff><institution xml:lang="en">Institute of Experimental Medicine</institution></aff><aff><institution xml:lang="ru">Федеральное государственное бюджетное научное учреждение «Институт экспериментальной медицины»</institution></aff></aff-alternatives><pub-date date-type="preprint" iso-8601-date="2021-03-23" publication-format="electronic"><day>23</day><month>03</month><year>2021</year></pub-date><pub-date date-type="pub" iso-8601-date="2021-06-10" publication-format="electronic"><day>10</day><month>06</month><year>2021</year></pub-date><volume>21</volume><issue>1</issue><issue-title xml:lang="en"/><issue-title xml:lang="ru"/><fpage>39</fpage><lpage>45</lpage><history><date date-type="received" iso-8601-date="2021-03-10"><day>10</day><month>03</month><year>2021</year></date><date date-type="accepted" iso-8601-date="2021-03-23"><day>23</day><month>03</month><year>2021</year></date></history><permissions><copyright-statement xml:lang="en">Copyright ©; 2021, Tanyanskiy D.A., Dizhe E.B., Oleinikova G.N., Shavva V.S., Denisenko A.D.</copyright-statement><copyright-statement xml:lang="ru">Copyright ©; 2021, Танянский Д.А., Диже Э.Б., Олейникова Г.Н., Шавва В.С., Денисенко А.Д.</copyright-statement><copyright-year>2021</copyright-year><copyright-holder xml:lang="en">Tanyanskiy D.A., Dizhe E.B., Oleinikova G.N., Shavva V.S., Denisenko A.D.</copyright-holder><copyright-holder xml:lang="ru">Танянский Д.А., Диже Э.Б., Олейникова Г.Н., Шавва В.С., Денисенко А.Д.</copyright-holder><license><ali:license_ref xmlns:ali="http://www.niso.org/schemas/ali/1.0/">https://creativecommons.org/licenses/by-nc-nd/4.0</ali:license_ref></license></permissions><self-uri xlink:href="https://journals.eco-vector.com/MAJ/article/view/62892">https://journals.eco-vector.com/MAJ/article/view/62892</self-uri><abstract xml:lang="en"><p><bold><italic>The aim of the study</italic></bold> was to find out the mechanisms of the adiponectin effect on apolipoproteins (apo) A-1 and B production by human hepatocytes.</p> <p><bold><italic>Materials and methods.</italic></bold> The study was performed on the human hepatoma cell line HepG2. The expression of the <italic>apoA-1</italic> gene was evaluated at the mRNA level by quantitative PCR with reverse transcription, and the production of apoB – by ELISA method. The activity of lipogenesis was assessed by the inclusion of labeled <sup>14</sup>C-acetate in triglycerides, as well as by mRNA expression of lipogenesis genes, and by the estimation of total triglycerides content in cells. To determine the involvement of signaling pathways, the RNA interference method was used.</p> <p><bold><italic>Results.</italic></bold> Knockdown of genes, coding the specific receptors, AMP-activated protein kinase, and its regulated transcription factors inhibited adiponectin-dependent stimulation of <italic>apoA-1</italic> gene expression in hepatocytes. Adiponectin had no effect on lipogenesis and apoB production under basal conditions, but suppressed these processes induced by the addition of oleate.</p> <p><bold><italic>Conclusion.</italic></bold> Adiponectin stimulates the production of apoA-1 in hepatocytes by inducing the transcription of the <italic>apoA-1</italic> gene and suppresses the secretion of apoB by affecting lipogenesis. These effects may underlie the effect of adiponectin on lipoproteins metabolism.</p></abstract><trans-abstract xml:lang="ru"><p><bold><italic>Цель исследования</italic></bold> — выяснить механизмы влияния адипонектина на продукцию аполипопротеинов (апо) А-1 и В гепатоцитами человека.</p> <p><bold><italic>Материалы и методы.</italic></bold> Исследование проводили на клетках линии гепатомы человека HepG2. Экспрессию гена <italic>apoA-1</italic> оценивали на уровне мРНК методом количественной полимеразной цепной реакции с обратной транскрипцией, продукцию апоВ — методом иммуноферментного анализа. Активность липогенеза определяли по включению меченого <sup>14</sup>С-ацетата в триглицериды, по экспрессии генов липогенеза на уровне мРНК и по общему содержанию триглицеридов в клетках. Для выяснения участия сигнальных путей использовали метод РНК-интерференции.</p> <p><bold><italic>Результаты.</italic></bold> Нокдаун генов специфических рецепторов, АМФ-активируемой протеинкиназы и регулируемых ею факторов транскрипции приводил к отмене адипонектин-зависимой стимуляции экспрессии гена <italic>apoA-1</italic> в гепатоцитах. Адипонектин не влиял на липогенез и продукцию апоВ в базальных условиях, но при этом подавлял данные процессы, индуцированные добавлением олеата.</p> <p><bold><italic>Заключение.</italic></bold> Адипонектин стимулирует продукцию апоА-1 в гепатоцитах путем индукции транскрипции гена <italic>apoA-1</italic> и подавляет секрецию данными клетками апоВ посредством влияния на липогенез. Указанные воздействия могут лежать в основе влияния адипонектина на обмен липопротеинов.</p></trans-abstract><kwd-group xml:lang="en"><kwd>adiponectin</kwd><kwd>apolipoproteins</kwd><kwd>hepatocytes</kwd><kwd>nuclear receptors</kwd><kwd>lipogenesis</kwd><kwd>metabolic syndrome</kwd></kwd-group><kwd-group xml:lang="ru"><kwd>адипонектин</kwd><kwd>аполипопротеины</kwd><kwd>гепатоциты</kwd><kwd>ядерные рецепторы</kwd><kwd>липогенез</kwd><kwd>метаболический синдром</kwd></kwd-group><funding-group><funding-statement xml:lang="en">The study was carried out with the financial support of the Russian Foundation for Basic Research within the framework of project No. 12-04-01410-a.</funding-statement><funding-statement xml:lang="ru">Исследование проведено при финансовой поддержке РФФИ в рамках проекта № 12-04-01410-а.</funding-statement></funding-group></article-meta></front><body></body><back><ref-list><ref id="B1"><label>1.</label><citation-alternatives><mixed-citation xml:lang="en">Mychka VB, Vertkin AL, Vardaev LI, et al. Experts’ consensus on the interdisciplinary approach towards the management, diagnostics, and treatment of patients with metabolic syndrome. Cardiovascular therapy and prevention. 2013;12 (6):41–81. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Мычка В.Б., Верткин А.Л., Вардаев Л.И. и др. Консенсус экспертов по междисциплинарному подходу к ведению, диагностике и лечению больных с метаболическим синдромом // Кардиоваскулярная терапия и профилактика. 2013. Т. 12, № 6. С. 41–81.</mixed-citation></citation-alternatives></ref><ref id="B2"><label>2.</label><citation-alternatives><mixed-citation xml:lang="en">Denisenko AD, Tanyansky DA. Adipokines in the pathogenesis of atherosclerosis in metabolic syndrome. In: Metabolic syndrome. Ed. by A.V. Shabrov. Saint Petersburg; 2020. P. 105–139. (In Russ.)</mixed-citation><mixed-citation xml:lang="ru">Денисенко А.Д., Танянский Д.А. Адипокины в патогенезе атеросклероза при метаболическом синдроме // Метаболический синдром / под ред. А.В. Шаброва. СПб., 2020. С. 105–139.</mixed-citation></citation-alternatives></ref><ref id="B3"><label>3.</label><citation-alternatives><mixed-citation xml:lang="en">Yamauchi T, Kamon J, Ito Y, et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects. Nature. 2003;423(6941):762–769. DOI: 10.1038/nature01705</mixed-citation><mixed-citation xml:lang="ru">Yamauchi T., Kamon J., Ito Y. et al. Cloning of adiponectin receptors that mediate antidiabetic metabolic effects // Nature. 2003. Vol. 423, No. 6941. P. 762–769. DOI: 10.1038/nature01705</mixed-citation></citation-alternatives></ref><ref id="B4"><label>4.</label><citation-alternatives><mixed-citation xml:lang="en">Qiao L, Zou C, van der Westhuyzen DR, Shao J. Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism. Diabetes. 2008;57(7):1824–1833. DOI: 10.2337/db07-0435</mixed-citation><mixed-citation xml:lang="ru">Qiao L., Zou C., van der Westhuyzen D.R., Shao J. Adiponectin reduces plasma triglyceride by increasing VLDL triglyceride catabolism // Diabetes. 2008. Vol. 57, No. 7. P. 1824–1833. DOI: 10.2337/db07-0435</mixed-citation></citation-alternatives></ref><ref id="B5"><label>5.</label><citation-alternatives><mixed-citation xml:lang="en">Matsuura F, Oku H, Koseki M, et al. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver. Biochem Biophys Res Commun. 2007;358(4):1091–1095. DOI: 10.1016/j.bbrc.2007.05.040</mixed-citation><mixed-citation xml:lang="ru">Matsuura F., Oku H., Koseki M. et al. Adiponectin accelerates reverse cholesterol transport by increasing high density lipoprotein assembly in the liver // Biochem. Biophys. Res. Commun. 2007. Vol. 358, No. 4. P. 1091–1095. DOI: 10.1016/j.bbrc.2007.05.040</mixed-citation></citation-alternatives></ref><ref id="B6"><label>6.</label><citation-alternatives><mixed-citation xml:lang="en">Wanninger J, Liebisch G, Eisinger K, et al. Adiponectin isoforms differentially affect gene expression and the lipidome of primary human hepatocytes. Metabolites. 2014;4(2):394–407. DOI: 10.3390/metabo4020394</mixed-citation><mixed-citation xml:lang="ru">Wanninger J., Liebisch G., Eisinger K. et al. Adiponectin isoforms differentially affect gene expression and the lipidome of primary human hepatocytes // Metabolites. 2014. Vol. 4, No. 2. P. 394–407. DOI: 10.3390/metabo4020394</mixed-citation></citation-alternatives></ref><ref id="B7"><label>7.</label><citation-alternatives><mixed-citation xml:lang="en">Wanninger J, Neumeier M, Weigert J, et al. Adiponectin-stimulated CXCL8 release in primary human hepatocytes is regulated by ERK1/ERK2, p38 MAPK, NF-kappaB, and STAT3 signaling pathways. Am J Physiol Gastrointest Liver Physiol. 2009;297(3):G611–G618. DOI: 10.1152/ajpgi.90644.2008</mixed-citation><mixed-citation xml:lang="ru">Wanninger J., Neumeier M., Weigert J. et al. Adiponectin-stimulated CXCL8 release in primary human hepatocytes is regulated by ERK1/ERK2, p38 MAPK, NF-kappaB, and STAT3 signaling pathways // Am. J. Physiol. Gastrointest. Liver Physiol. 2009. Vol. 297, No. 3. P. G611–G618. DOI: 10.1152/ajpgi.90644.2008</mixed-citation></citation-alternatives></ref><ref id="B8"><label>8.</label><citation-alternatives><mixed-citation xml:lang="en">Shavva VS, Bogomolova AM, Nikitin AA, et al. FOXO1 and LXRα downregulate the apolipoprotein A-I gene expression during hydrogen peroxide-induced oxidative stress in HepG2 cells. Cell Stress Chaperones. 2017;22(1):123–134. DOI: 10.1007/s12192-016-0749-6</mixed-citation><mixed-citation xml:lang="ru">Shavva V.S., Bogomolova A.M., Nikitin A.A. et al. FOXO1 and LXRα downregulate the apolipoprotein A-I gene expression during hydrogen peroxide-induced oxidative stress in HepG2 cells // Cell Stress Chaperones. 2017. Vol. 22, No. 1. P. 123–134. DOI: 10.1007/s12192-016-0749-6</mixed-citation></citation-alternatives></ref><ref id="B9"><label>9.</label><citation-alternatives><mixed-citation xml:lang="en">Mogilenko DA, Dizhe EB, Shavva VS, et al. Role of the nuclear receptors HNF4 alpha, PPAR alpha, and LXRs in the TNF alpha-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells. Biochemistry. 2009;48(50):11950–11960. DOI: 10.1021/bi9015742</mixed-citation><mixed-citation xml:lang="ru">Mogilenko D.A., Dizhe E.B., Shavva V.S. et al. Role of the nuclear receptors HNF4 alpha, PPAR alpha, and LXRs in the TNF alpha-mediated inhibition of human apolipoprotein A-I gene expression in HepG2 cells // Biochemistry. 2009. Vol.48, No. 50. P. 11950–11960. DOI: 10.1021/bi9015742</mixed-citation></citation-alternatives></ref><ref id="B10"><label>10.</label><citation-alternatives><mixed-citation xml:lang="en">Nekrasova EV, Danko KV, Shavva VS, et al. Effect of the insulin on the apolipoprotein A-I gene expression in human macrophages. Medical Academic Journal. 2020;20(1):65–74. (In Russ.). DOI: 10.17816/MAJ16437</mixed-citation><mixed-citation xml:lang="ru">Некрасова Е.В., Данько Е.В., Шавва В.С. и др. Действие инсулина на экспрессию гена аполипопротеина A-I в макрофагах человека // Медицинский академический журнал. 2020. Т. 20, № 1. C. 65–74. DOI: 10.17816/MAJ16437</mixed-citation></citation-alternatives></ref><ref id="B11"><label>11.</label><citation-alternatives><mixed-citation xml:lang="en">Lee J, Hong SW, Park SE, et al. AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells. Mol Cell Endocrinol. 2015;414:148–155. DOI: 10.1016/j.mce.2015.07.031</mixed-citation><mixed-citation xml:lang="ru">Lee J., Hong S.W., Park S.E. et al. AMP-activated protein kinase suppresses the expression of LXR/SREBP-1 signaling-induced ANGPTL8 in HepG2 cells // Mol. Cell. Endocrinol. 2015. Vol. 414. P. 148–155. DOI: 10.1016/j.mce.2015.07.031</mixed-citation></citation-alternatives></ref><ref id="B12"><label>12.</label><citation-alternatives><mixed-citation xml:lang="en">Hwahng SH, Ki SH, Bae EJ, et al. Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones. Hepatology. 2009;49(6):1913–1925. DOI: 10.1002/hep.22887</mixed-citation><mixed-citation xml:lang="ru">Hwahng S.H., Ki S.H., Bae E.J. et al. Role of adenosine monophosphate-activated protein kinase-p70 ribosomal S6 kinase-1 pathway in repression of liver X receptor-alpha-dependent lipogenic gene induction and hepatic steatosis by a novel class of dithiolethiones // Hepatology. 2009. Vol. 49, No. 6. P. 1913–1925. DOI: 10.1002/hep.22887</mixed-citation></citation-alternatives></ref><ref id="B13"><label>13.</label><citation-alternatives><mixed-citation xml:lang="en">Fazio S, Linton MF. Regulation and clearance of apolipoprotein B-containing lipoproteins. In: Clinical lipidology: a companion to Braunwald’s heart disease. Ed by C.M. Ballantyne. 2nd ed. Sauders Elsevier; 2015: 11–24. DOI: 10.1016/B978-141605469-6.50006-8</mixed-citation><mixed-citation xml:lang="ru">Fazio S., Linton M.F. Regulation and clearance of apolipoprotein B-containing lipoproteins // Clinical lipidology: a companion to Braunwald’s heart disease. Ed by C.M. Ballantyne. 2nd ed. Sauders Elsevier; 2015. P. 11–24. DOI: 10.1016/B978-141605469-6.50006-8</mixed-citation></citation-alternatives></ref><ref id="B14"><label>14.</label><citation-alternatives><mixed-citation xml:lang="en">Awazawa M, Ueki K, Inabe K, et al. Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway. Biochem Biophys Res Commun. 2009;382(1):51–56. DOI: 10.1016/j.bbrc.2009.02.131</mixed-citation><mixed-citation xml:lang="ru">Awazawa M., Ueki K., Inabe K. et al. Adiponectin suppresses hepatic SREBP1c expression in an AdipoR1/LKB1/AMPK dependent pathway // Biochem. Biophys. Res. Commun. 2009. Vol. 382, No. 1. P. 51–56. DOI: 10.1016/j.bbrc.2009.02.131</mixed-citation></citation-alternatives></ref><ref id="B15"><label>15.</label><citation-alternatives><mixed-citation xml:lang="en">Chen H, Zhang L, Li X, et al. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes. J Steroid Biochem Mol Biol. 2013;138:445–454. DOI: 10.1016/j.jsbmb.2013.08.013</mixed-citation><mixed-citation xml:lang="ru">Chen H., Zhang L., Li X. et al. Adiponectin activates the AMPK signaling pathway to regulate lipid metabolism in bovine hepatocytes // J. Steroid. Biochem. Mol. Biol. 2013. Vol. 138. P. 445–454. DOI: 10.1016/j.jsbmb.2013.08.013</mixed-citation></citation-alternatives></ref><ref id="B16"><label>16.</label><citation-alternatives><mixed-citation xml:lang="en">Garcia D, Shaw RJ. AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance. Mol Cell. 2017;66(6):789–800. DOI: 10.1016/j.molcel.2017.05.032</mixed-citation><mixed-citation xml:lang="ru">Garcia D., Shaw R.J. AMPK: Mechanisms of cellular energy sensing and restoration of metabolic balance // Mol. Cell. 2017. Vol. 66, No. 6. P. 789–800. DOI: 10.1016/j.molcel.2017.05.032</mixed-citation></citation-alternatives></ref><ref id="B17"><label>17.</label><citation-alternatives><mixed-citation xml:lang="en">Iwabu M, Yamauchi T, Okada-Iwabu M, et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1. Nature. 2010;464(7293):1313–1319. DOI: 10.1038/nature08991</mixed-citation><mixed-citation xml:lang="ru">Iwabu M., Yamauchi T., Okada-Iwabu M. et al. Adiponectin and AdipoR1 regulate PGC-1alpha and mitochondria by Ca(2+) and AMPK/SIRT1 // Nature. 2010. Vol. 464, No. 7293. P. 1313–1319. DOI: 10.1038/nature08991</mixed-citation></citation-alternatives></ref></ref-list></back></article>
