دورية أكاديمية
Sacubitril/valsartan promotes white adipose tissue browning in rats with metabolic syndrome through activation of mTORC1.
العنوان: | Sacubitril/valsartan promotes white adipose tissue browning in rats with metabolic syndrome through activation of mTORC1. |
---|---|
المؤلفون: | Nikolic M; Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia., Jeremic N; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Federal State Autonomous Educational Institution of Higher Education I.M. Sechenov First Moscow State Medical University of the Ministry of Health of the Russian Federation (Sechenov University), Moscow, Russia., Lazarevic N; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Department of Human Pathology, 1st Moscow State Medical, University IM Sechenov, Moscow, Russia., Stojanovic A; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Milojevic Samanovic A; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Dentistry, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Novakovic J; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Zivkovic V; Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Pharmacology, I.M. Sechenov First Moscow State Medical University, Moscow, Russia., Nikolic M; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Nedeljkovic N; Department of Pharmacy, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Mitrovic S; Department of Pathology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia., Jakovljevic V; Department of Physiology, Faculty of Medical Sciences, University of Kragujevac, Kragujevac, Serbia.; Center of Excellence for Redox Balance Research in Cardiovascular and Metabolic Disorders, Kragujevac, Serbia.; Department of Human Pathology, 1st Moscow State Medical, University IM Sechenov, Moscow, Russia. |
المصدر: | BioFactors (Oxford, England) [Biofactors] 2024 Jul-Aug; Vol. 50 (4), pp. 772-793. Date of Electronic Publication: 2024 Jan 29. |
نوع المنشور: | Journal Article |
اللغة: | English |
بيانات الدورية: | Publisher: Ios Press Country of Publication: Netherlands NLM ID: 8807441 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1872-8081 (Electronic) Linking ISSN: 09516433 NLM ISO Abbreviation: Biofactors Subsets: MEDLINE |
أسماء مطبوعة: | Publication: Amsterdam : Ios Press Original Publication: Oxford ; Washington, DC : Published for the International Union of Biochemistry by IRL Press, [c1988- |
مواضيع طبية MeSH: | Valsartan*/pharmacology , Biphenyl Compounds*/pharmacology , Adipose Tissue, White*/drug effects , Adipose Tissue, White*/metabolism , Metabolic Syndrome*/drug therapy , Metabolic Syndrome*/metabolism , Metabolic Syndrome*/pathology , Drug Combinations* , Aminobutyrates*/pharmacology , Rats, Wistar* , Mechanistic Target of Rapamycin Complex 1*/metabolism , Mechanistic Target of Rapamycin Complex 1*/antagonists & inhibitors , Mechanistic Target of Rapamycin Complex 1*/genetics , Tetrazoles*/pharmacology , Molecular Docking Simulation*, Animals ; Male ; Rats ; Adipose Tissue, Brown/drug effects ; Adipose Tissue, Brown/metabolism ; Uncoupling Protein 1/metabolism ; Uncoupling Protein 1/genetics ; Molecular Dynamics Simulation ; Neprilysin/metabolism ; Neprilysin/genetics ; Neprilysin/antagonists & inhibitors |
مستخلص: | In addition to their usual use in the treatment of cardiovascular disease, weak evidence is available for the potential of combined use of neprilysin inhibitor (sacubitril) and AT1 receptor antagonist (valsartan) to promote browning of white adipose tissue (WAT) in rats with metabolic syndrome (MetS). This study involved 32 male Wistar albino rats divided into four groups: CTRL-healthy control rats; ENT-healthy rats treated with sacubitril/valsartan; MS-rats with MetS; MS + ENT-rats with MetS treated with sacubitril/valsartan. After finishing the experimental protocol, different WAT depots were isolated for further analysis of molecular pathways. Molecular docking and molecular dynamics studies were used for in silico assessment of the binding affinity of sacubitril and valsartan towards subunits of mechanistic target of rapamycin complex 1 (mTORC1). Sacubitril/valsartan treatment markedly diminished morphological changes in adipose tissue, resulting in smaller lipid size and multilocular lipid droplet structure in WAT. We showed significantly higher protein expression of uncoupling protein-1 (UCP-1) and mTORC1 in WAT of MS + ENT rats, correlating with increased relative gene expression of browning-related markers in tissue of rats treated with sacubitril/valsartan compared with MS group of rats. In silico analysis showed that sacubitrilat and valsartan exhibited the highest binding affinity against mTOR and mLST8, forming stable complexes with these mTORC1 subunits. The observed results confirmed strong potential of combined sacubitril/valsartan treatment to increase browning markers expression in different WAT depots in MetS condition and to form permanent complexes with mTOR and mLST8 subunits over the time. (© 2024 International Union of Biochemistry and Molecular Biology.) |
References: | Machado SA, Pasquarelli‐do‐Nascimento G, da Silva DS, Farias GR, de Oliveira Santos I, Baptista LB, et al. Browning of the white adipose tissue regulation: new insights into nutritional and metabolic relevance in health and diseases. Nutr Metab. 2022;19(1):61. Keshvari S, Ceddia RP, Rajbhandari P, Chaurasia B, Bond ST. Editorial: adipose tissue in obesity and metabolic disease. Front Physiol. 2022;13:898861. Longo M, Zatterale F, Naderi J, Parrillo L, Formisano P, Raciti GA, et al. Adipose tissue dysfunction as determinant of obesity‐associated metabolic complications. Int J Mol Sci. 2019;20(9):2358. Kahn CR, Wang G, Lee KY. Altered adipose tissue and adipocyte function in the pathogenesis of metabolic syndrome. J Clin Invest. 2019;129(10):3990–4000. Nikolic M, Novakovic J, Ramenskaya G, Kokorekin V, Jeremic N, Jakovljevic V. Cooling down with Entresto. Can sacubitril/valsartan combination enhance browning more than coldness? Diabetol Metab Syndr. 2022;14(1):175. Chait A, den Hartigh LJ. Adipose tissue distribution, inflammation and its metabolic consequences, including diabetes and cardiovascular disease. Frontiers Cardiovasc Med. 2020;7:22. Cai Z, Fang L, Jiang Y, Liang M, Wang J, Shen Y, et al. Angiotensin II promotes white adipose tissue Browning and Lipolysis in mice. Oxid Med Cell Longev. 2022;2022:6022601. Harms M, Seale P. Brown and beige fat: development, function and therapeutic potential. Nat Med. 2013;19(10):1252–1263. Kuryłowicz A, Puzianowska‐Kuźnicka M. Induction of adipose tissue Browning as a strategy to combat obesity. Int J Mol Sci. 2020;21(17):6241. Karastergiou K, Mohamed‐Ali V. The autocrine and paracrine roles of adipokines. Mol Cell Endocrinol. 2010;318(1–2):69–78. Sahu B, Bal NC. Adipokines from white adipose tissue in regulation of whole body energy homeostasis. Biochimie. 2023;204:92–107. Nagoshi T. Close linkage between natriuretic peptides and obesity – impact of sex on the Interorgan metabolic crosstalk. Circ J. 2021;85(5):655–656. Carper D, Coué M, Nascimento EBM, Barquissau V, Lagarde D, Pestourie C, et al. Atrial natriuretic peptide orchestrates a coordinated physiological response to fuel non‐shivering thermogenesis. Cell Rep. 2020;32(8):108075. Kimura H, Nagoshi T, Oi Y, Yoshii A, Tanaka Y, Takahashi H, et al. Treatment with atrial natriuretic peptide induces adipose tissue browning and exerts thermogenic actions in vivo. Sci Rep. 2021;11(1):17466. Wu W, Shi F, Liu D, Ceddia RP, Gaffin R, Wei W, et al. Enhancing natriuretic peptide signaling in adipose tissue, but not in muscle, protects against diet‐induced obesity and insulin resistance. Sci Signal. 2017;10(489):eaam6870. Kim DY, Choi MJ, Ko TK, Lee NH, Kim OH, Cheon HG. Angiotensin AT1 receptor antagonism by losartan stimulates adipocyte browning via induction of apelin. J Biol Chem. 2020;295(44):14878–14892. Graus‐Nunes F, Rachid TL, de Oliveira Santos F, Barbosa‐da‐Silva S, Souza‐Mello V. AT1 receptor antagonist induces thermogenic beige adipocytes in the inguinal white adipose tissue of obese mice. Endocrine. 2017;55(3):786–798. Liu HM, Wang CH, Chang ZY, Huang TH, Lee TY. Losartan attenuates insulin resistance and regulates Browning phenomenon of white adipose tissue in ob/ob mice. Curr Issues Mol Biol. 2021;43(3):1828–1843. Than A, Xu S, Li R, Leow MK, Sun L, Chen P. Angiotensin type 2 receptor activation promotes browning of white adipose tissue and brown adipogenesis. Signal Transduct Target Ther. 2017;2:17022. Jeremic JN, Jakovljevic VL, Zivkovic VI, Srejovic IM, Bradic JV, Milosavljevic IM, et al. Garlic derived diallyl trisulfide in experimental metabolic syndrome: metabolic effects and Cardioprotective role. Int J Mol Sci. 2020;21(23):9100. Davidson EP, Coppey LJ, Shevalye H, Obrosov A, Yorek MA. Vascular and neural complications in type 2 diabetic rats: improvement by Sacubitril/valsartan greater Than valsartan alone. Diabetes. 2018;67(8):1616–1626. Sobot NM, Sobot TS, Jeremic JN, Bolevich SB, Bolevich SS, Mitrovic SL, et al. Minocycline as heart conditioning agent in experimental type 2 diabetes mellitus – an antibacterial drug in heart protection. Naunyn Schmiedebergs Arch Pharmacol. 2022;395(4):429–444. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real‐time quantitative PCR and the 2(‐Delta Delta C(T)) method. Methods. 2001;25(4):402–408. Morris GM, Ruth H, Lindstrom W, Sanner MF, Belew RK, Goodsell DS, et al. AutoDock4 and AutoDockTools4: automated docking with selective receptor flexibility. J Comput Chem. 2009;30(16):2785–2791. ChemOffice Ultra 7.0.1. Cambridge, MA, USA: CambridgeSoft Corporation; 2002. Available from: http://www.cambridgesoft.com. Yang H, Jiang X, Li B, Yang HJ, Miller M, Yang A, et al. Mechanisms of mTORC1 activation by RHEB and inhibition by PRAS40. Nature. 2017;552(7685):368–373. Protein Data Bank [cited 2023 May 5]. Available from: http://www.rcsb.org/. BIOVIA. Dassault Systèmes, Discovery studio visualizer, 17.2.0.16349. San Diego: Dassault Systèmes; 2016. Schrödinger L, DeLano W. PyMOL [cited 2023 May 5]. Available from: https://www.pymol.org/pymol. Schrödinger Release 2020‐4. Desmond molecular dynamics system. New York: D. E. Shaw Research; 2020. Harder E, Damm W, Maple J, Wu C, Reboul M, Xiang JY, et al. OPLS3: a force field providing broad coverage of drug‐like small molecules and proteins. J Chem Theory Comput. 2016;12(1):281–296. Jorgensen WL, Chandrasekhar J, Madura JD, Impey RW, Klein ML. Comparison of simple potential functions for simulating liquid water. J Cheml Phys. 1983;79(2):926–935. Genheden S, Ryde U. The MM/PBSA and MM/GBSA methods to estimate ligand‐binding affinities. Expert Opin Drug Discov. 2015;10(5):449–461. Wijkman MO, Claggett B, Vaduganathan M, Cunningham JW, Rørth R, Jackson A, et al. Effects of sacubitril/valsartan on glycemia in patients with diabetes and heart failure: the PARAGON‐HF and PARADIGM‐HF trials. Cardiovasc Diabetol. 2022;21(1):110. Bremer AA, Devaraj S, Afify A, Jialal I. Adipose tissue dysregulation in patients with metabolic syndrome. J Clin Endocrinol Metab. 2011;96(11):E1782–E1788. Perrone‐Filardi P, Paolillo S, Costanzo P, Savarese G, Trimarco B, Bonow RO. The role of metabolic syndrome in heart failure. Eur Heart J. 2015;36(39):2630–2634. Cloro C, Zaffina I, Sacchetta L, Arturi F, Clausi C, Lucà S, et al. Effects of sacubitril/valsartan on both metabolic parameters and insulin resistance in prediabetic non‐obese patients with heart failure and reduced ejection fraction. Front Endocrinol. 2022;13:940654. Cheng KC, Li Y, Chang WT, Kuo FY, Chen ZC, Cheng JT. Telmisartan is effective to ameliorate metabolic syndrome in rat model – a preclinical report. Diabetes Metab Syndr Obes. 2018;11:901–911. Michel MC, Brunner HR, Foster C, Huo Y. Angiotensin II type 1 receptor antagonists in animal models of vascular, cardiac, metabolic and renal disease. Pharmacol Ther. 2016;164:1–81. Santhekadur PK, Kumar DP, Seneshaw M, Mirshahi F, Sanyal AJ. The multifaceted role of natriuretic peptides in metabolic syndrome. Biomed Pharmacother. 2017;92:826–835. Michel MC, Bohner H, Köster J, Schäfers R, Heemann U. Safety of telmisartan in patients with arterial hypertension: an open‐label observational study. Drug Saf. 2004;27(5):335–344. Selvaraj S, Claggett BL, Packer M, Zannad F, Anand IS, Pieske B, et al. Effects of Sacubitril/valsartan on serum lipids in heart failure with preserved ejection fraction. J Am Heart Assoc. 2021;10(17):e022069. Verboven K, Hansen D, Jocken JWE, Blaak EE. Natriuretic peptides in the control of lipid metabolism and insulin sensitivity. Obes Rev. 2017;18(11):1243–1259. Rubattu S, Sciarretta S, Valenti V, Stanzione R, Volpe M. Natriuretic peptides: an update on bioactivity, potential therapeutic use, and implication in cardiovascular diseases. Am J Hypertens. 2008;21(7):733–741. Esser N, Mongovin SM, Parilla J, Barrow BM, Mundinger TO, Fountaine BS, et al. Neprilysin inhibition improves intravenous but not oral glucose‐mediated insulin secretion via GLP‐1R signaling in mice with β‐cell dysfunction. Am J Physiol Endocrinol Metab. 2022;322(3):E307–E318. Armentaro G, D'Arrigo G, Miceli S, Cassano V, Perticone M, Maio R, et al. Long term metabolic effects of Sacubitril/valsartan in non‐diabetic and diabetic patients with heart failure reduced ejection fraction: a real life study. Front Physiol. 2022;13:897109. Willard JR, Barrow BM, Zraika S. Improved glycaemia in high‐fat‐fed neprilysin‐deficient mice is associated with reduced DPP‐4 activity and increased active GLP‐1 levels. Diabetologia. 2017;60(4):701–708. Liu D, Ceddia RP, Collins S. Cardiac natriuretic peptides promote adipose ‘browning’ through mTOR complex‐1. Mol Metab. 2018;9:192–198. Reverte‐Salisa L, Sanyal A, Pfeifer A. Role of cAMP and cGMP signaling in Brown fat. Handb Exp Pharmacol. 2019;251:161–182. Moro C, Lafontan M. Natriuretic peptides and cGMP signaling control of energy homeostasis. Am J Physiol Heart Circ Physiol. 2012;304(3):H358–H368. Glöde A, Naumann J, Gnad T, Cannone V, Kilic A, Burnett JC Jr, et al. Divergent effects of a designer natriuretic peptide CD‐NP in the regulation of adipose tissue and metabolism. Mol Metab. 2017;6:276–287. Ye Y, Liu H, Zhang F, Hu F. mTOR signaling in Brown and Beige adipocytes: implications for thermogenesis and obesity. Nutr Metab. 2019;16:74. Kang NH, Mukherjee S, Jang MH, Pham HG, Choi M, Yun JW. Ketoprofen alleviates diet‐induced obesity and promotes white fat browning in mice via the activation of COX‐2 through mTORC1‐p38 signaling pathway. Pflug Arch. 2020;472(5):583–596. Francés DE, Motiño O, Agrá N, González‐Rodríguez Á, Fernández‐Álvarez A, Cucarella C, et al. Hepatic cyclooxygenase‐2 expression protects against diet‐induced steatosis, obesity, and insulin resistance. Diabetes. 2015;64(5):1522–1531. García‐Alonso V, Titos E, Alcaraz‐Quiles J, Rius B, Lopategi A, López‐Vicario C, et al. Prostaglandin E2 exerts multiple regulatory actions on human obese adipose tissue remodeling, inflammation, adaptive thermogenesis and lipolysis. PLoS One. 2016;11(4):e0153751. Tsukuda K, Mogi M, Iwanami J, Kanno H, Nakaoka H, Wang XL, et al. Enhancement of adipocyte Browning by angiotensin II type 1 receptor blockade. PloS One. 2016;11(12):e0167704. Kobayashi M, Deguchi Y, Nozaki Y, Higami Y. Contribution of PGC‐1α to obesity‐ and caloric restriction‐related physiological changes in white adipose tissue. Int J Mol Sci. 2021;22(11):6025. Torres PHM, Sodero ACR, Jofily P, Silva‐Jr FP. Key topics in molecular docking for drug design. Int J Mol Sci. 2019;20(18):4574. |
معلومات مُعتمدة: | 04/22 Faculty of Medical Science, University of Kragujevac; 451-03-47/2023-01/200111 Ministry of Science, Technological Development and Innovation, Republic of Serbia |
فهرسة مساهمة: | Keywords: adipose tissue; browning; molecular docking; sacubitril; valsartan |
المشرفين على المادة: | 80M03YXJ7I (Valsartan) 0 (Biphenyl Compounds) 0 (Drug Combinations) 0 (Aminobutyrates) WB8FT61183 (sacubitril and valsartan sodium hydrate drug combination) EC 2.7.11.1 (Mechanistic Target of Rapamycin Complex 1) 0 (Tetrazoles) 0 (Uncoupling Protein 1) EC 3.4.24.11 (Neprilysin) |
تواريخ الأحداث: | Date Created: 20240129 Date Completed: 20240808 Latest Revision: 20240808 |
رمز التحديث: | 20240808 |
DOI: | 10.1002/biof.2040 |
PMID: | 38284316 |
قاعدة البيانات: | MEDLINE |
تدمد: | 1872-8081 |
---|---|
DOI: | 10.1002/biof.2040 |