Carvedilol improves glucose tolerance and insulin sensitivity in treatment of adrenergic overdrive in high fat diet-induced obesity in mice
Autoři:
Linh V. Nguyen aff001; Quang V. Ta aff002; Thao B. Dang aff001; Phu H. Nguyen aff003; Thach Nguyen aff001; Thi Van Huyen Pham aff001; Trang HT. Nguyen aff004; Stephen Baker aff004; Trung Le Tran aff005; Dong Joo Yang aff005; Ki Woo Kim aff005; Khanh V. Doan aff001
Působiště autorů:
School of Medicine, Tan Tao University, Long An, Viet Nam
aff001; School of Biotechnology, Tan Tao University, Long An, Viet Nam
aff002; Binh Dan Hospital, Ho Chi Minh, Viet Nam
aff003; Oxford University Clinical Research Unit in Viet Nam, Ho Chi Minh, Viet Nam
aff004; Division of Physiology, Department of Oral Biology, BK21 PLUS, Yonsei University College of Dentistry, Seoul, South Korea
aff005
Vyšlo v časopise:
PLoS ONE 14(11)
Kategorie:
Research Article
prolekare.web.journal.doi_sk:
https://doi.org/10.1371/journal.pone.0224674
Souhrn
Catecholamine excess reflecting an adrenergic overdrive of the sympathetic nervous system (SNS) has been proposed to link to hyperleptinemia in obesity and may contribute to the development of metabolic disorders. However, relationship between the catecholamine level and plasma leptin in obesity has not yet been investigated. Moreover, whether pharmacological blockade of the adrenergic overdrive in obesity by the third-generation beta-blocker agents such as carvedilol could help to prevent metabolic disorders is controversial and remains to be determined. Using the high fat diet (HFD)-induced obese mouse model, we found that basal plasma norepinephrine, the principal catecholamine as an index of SNS activity, was persistently elevated and highly correlated with plasma leptin concentration during obesity development. Targeting the adrenergic overdrive from this chronic norepinephrine excess in HFD-induced obesity with carvedilol, a third-generation beta-blocker with vasodilating action, blunted the HFD-induced hepatic glucose over-production by suppressing the induction of gluconeogenic enzymes, and enhanced the muscular insulin signaling pathway. Furthermore, carvedilol treatment in HFD-induced obese mice decreased the enlargement of white adipose tissue and improved the glucose tolerance and insulin sensitivity without affecting body weight and blood glucose levels. Our results suggested that catecholamine excess in obesity might directly link to the hyperleptinemic condition and the therapeutic targeting of chronic adrenergic overdrive in obesity with carvedilol might be helpful to attenuate obesity-related metabolic disorders.
Klíčová slova:
leptin – Body weight – Insulin – Glucose metabolism – Blood plasma – Obesity – Catecholamines – Norepinephrine
Zdroje
1. Ng M, Fleming T, Robinson M, Thomson B, Graetz N, Margono C, et al. Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014;384(9945):766–81. doi: 10.1016/S0140-6736(14)60460-8 24880830.
2. Smith MM, Minson CT. Obesity and adipokines: effects on sympathetic overactivity. J Physiol. 2012;590(8):1787–801. Epub 2012/02/22. doi: 10.1113/jphysiol.2011.221036 22351630; PubMed Central PMCID: PMC3573303.
3. Hall JE, do Carmo JM, da Silva AA, Wang Z, Hall ME. Obesity-induced hypertension: interaction of neurohumoral and renal mechanisms. Circ Res. 2015;116(6):991–1006. doi: 10.1161/CIRCRESAHA.116.305697 25767285; PubMed Central PMCID: PMC4363087.
4. Seravalle G, Grassi G. Sympathetic Nervous System, Hypertension, Obesity and Metabolic Syndrome. High Blood Press Cardiovasc Prev. 2016;23(3):175–9. Epub 2016/03/05. doi: 10.1007/s40292-016-0137-4 26942609.
5. Mancia G, Bousquet P, Elghozi JL, Esler M, Grassi G, Julius S, et al. The sympathetic nervous system and the metabolic syndrome. J Hypertens. 2007;25(5):909–20. Epub 2007/04/07. doi: 10.1097/HJH.0b013e328048d004 17414649.
6. Schlaich M, Straznicky N, Lambert E, Lambert G. Metabolic syndrome: a sympathetic disease? Lancet Diabetes Endocrinol. 2015;3(2):148–57. Epub 2014/04/16. doi: 10.1016/S2213-8587(14)70033-6 24731670.
7. Moreira MC, Pinto IS, Mourao AA, Fajemiroye JO, Colombari E, Reis AA, et al. Does the sympathetic nervous system contribute to the pathophysiology of metabolic syndrome? Front Physiol. 2015;6:234. Epub 2015/09/18. doi: 10.3389/fphys.2015.00234 26379553; PubMed Central PMCID: PMC4548210.
8. Osorio J. Obesity: The many faces of leptin—a novel role for leptin signalling in obesity-induced hypertension. Nat Rev Endocrinol. 2015;11(3):129. doi: 10.1038/nrendo.2014.231 25534200.
9. Simonds SE, Cowley MA. Hypertension in obesity: is leptin the culprit? Trends Neurosci. 2013;36(2):121–32. doi: 10.1016/j.tins.2013.01.004 23333346.
10. Simonds SE, Pryor JT, Ravussin E, Greenway FL, Dileone R, Allen AM, et al. Leptin mediates the increase in blood pressure associated with obesity. Cell. 2014;159(6):1404–16. doi: 10.1016/j.cell.2014.10.058 25480301; PubMed Central PMCID: PMC4259491.
11. Luan B, Goodarzi MO, Phillips NG, Guo X, Chen YD, Yao J, et al. Leptin-mediated increases in catecholamine signaling reduce adipose tissue inflammation via activation of macrophage HDAC4. Cell metabolism. 2014;19(6):1058–65. doi: 10.1016/j.cmet.2014.03.024 24768298; PubMed Central PMCID: PMC4207085.
12. Zeng W, Pirzgalska RM, Pereira MM, Kubasova N, Barateiro A, Seixas E, et al. Sympathetic neuro-adipose connections mediate leptin-driven lipolysis. Cell. 2015;163(1):84–94. doi: 10.1016/j.cell.2015.08.055 26406372.
13. Carlyle M, Jones OB, Kuo JJ, Hall JE. Chronic cardiovascular and renal actions of leptin: role of adrenergic activity. Hypertension. 2002;39(2 Pt 2):496–501. doi: 10.1161/hy0202.104398 11882597.
14. Mark AL, Agassandian K, Morgan DA, Liu X, Cassell MD, Rahmouni K. Leptin signaling in the nucleus tractus solitarii increases sympathetic nerve activity to the kidney. Hypertension. 2009;53(2):375–80. doi: 10.1161/HYPERTENSIONAHA.108.124255 19103999; PubMed Central PMCID: PMC2688398.
15. Takekoshi K, Motooka M, Isobe K, Nomura F, Manmoku T, Ishii K, et al. Leptin directly stimulates catecholamine secretion and synthesis in cultured porcine adrenal medullary chromaffin cells. Biochemical and biophysical research communications. 1999;261(2):426–31. doi: 10.1006/bbrc.1999.1025 10425201.
16. Takekoshi K, Ishii K, Kawakami Y, Isobe K, Nanmoku T, Nakai T. Ca(2+) mobilization, tyrosine hydroxylase activity, and signaling mechanisms in cultured porcine adrenal medullary chromaffin cells: effects of leptin. Endocrinology. 2001;142(1):290–8. doi: 10.1210/endo.142.1.7914 11145592.
17. Takekoshi K, Ishii K, Nanmoku T, Shibuya S, Kawakami Y, Isobe K, et al. Leptin stimulates catecholamine synthesis in a PKC-dependent manner in cultured porcine adrenal medullary chromaffin cells. Endocrinology. 2001;142(11):4861–71. doi: 10.1210/endo.142.11.8484 11606454.
18. Utsunomiya K, Yanagihara N, Tachikawa E, Cheah TB, Kajiwara K, Toyohira Y, et al. Stimulation of catecholamine synthesis in cultured bovine adrenal medullary cells by leptin. Journal of neurochemistry. 2001;76(3):926–34. doi: 10.1046/j.1471-4159.2001.00123.x 11158265.
19. Shibuya I, Utsunomiya K, Toyohira Y, Ueno S, Tsutsui M, Cheah TB, et al. Regulation of catecholamine synthesis by leptin. Annals of the New York Academy of Sciences. 2002;971:522–7. doi: 10.1111/j.1749-6632.2002.tb04517.x 12438173.
20. Satoh N, Ogawa Y, Katsuura G, Numata Y, Tsuji T, Hayase M, et al. Sympathetic activation of leptin via the ventromedial hypothalamus: leptin-induced increase in catecholamine secretion. Diabetes. 1999;48(9):1787–93. doi: 10.2337/diabetes.48.9.1787 10480609.
21. Son DH, Doan KV, Yang DJ, Sun JS, Kim SK, Kang N, et al. FoxO1 regulates leptin-induced mood behavior by targeting tyrosine hydroxylase. Metabolism. 2018. Epub 2018/12/01. doi: 10.1016/j.metabol.2018.11.013 30500562.
22. Kvetnansky R, Sabban EL, Palkovits M. Catecholaminergic systems in stress: structural and molecular genetic approaches. Physiological reviews. 2009;89(2):535–606. doi: 10.1152/physrev.00042.2006 19342614.
23. Goldstein DS. The Autonomic Nervous System in Health and Disease (Neurological Disease and Therapy). New York: CRC Press; 2000.
24. Spiegel A, Kalinkovich A, Shivtiel S, Kollet O, Lapidot T. Stem cell regulation via dynamic interactions of the nervous and immune systems with the microenvironment. Cell stem cell. 2008;3(5):484–92. doi: 10.1016/j.stem.2008.10.006 18983964.
25. Petrak O, Haluzikova D, Kavalkova P, Strauch B, Rosa J, Holaj R, et al. Changes in energy metabolism in pheochromocytoma. J Clin Endocrinol Metab. 2013;98(4):1651–8. Epub 2013/02/26. doi: 10.1210/jc.2012-3625 23436923.
26. Barth E, Albuszies G, Baumgart K, Matejovic M, Wachter U, Vogt J, et al. Glucose metabolism and catecholamines. Crit Care Med. 2007;35(9 Suppl):S508–18. Epub 2007/09/22. doi: 10.1097/01.CCM.0000278047.06965.20 17713401.
27. Weber MA. The role of the new beta-blockers in treating cardiovascular disease. American journal of hypertension. 2005;18(12 Pt 2):169S–76S. doi: 10.1016/j.amjhyper.2005.09.009 16373195.
28. Wiysonge CS, Bradley H, Mayosi BM, Maroney R, Mbewu A, Opie LH, et al. Beta-blockers for hypertension. The Cochrane database of systematic reviews. 2007;(1):CD002003. doi: 10.1002/14651858.CD002003.pub2 17253471.
29. Dahlof B, Devereux RB, Kjeldsen SE, Julius S, Beevers G, de Faire U, et al. Cardiovascular morbidity and mortality in the Losartan Intervention For Endpoint reduction in hypertension study (LIFE): a randomised trial against atenolol. Lancet. 2002;359(9311):995–1003. doi: 10.1016/S0140-6736(02)08089-3 11937178.
30. Ripley TL, Saseen JJ. beta-blockers: a review of their pharmacological and physiological diversity in hypertension. The Annals of pharmacotherapy. 2014;48(6):723–33. doi: 10.1177/1060028013519591 24687542.
31. Deedwania P. Hypertension, dyslipidemia, and insulin resistance in patients with diabetes mellitus or the cardiometabolic syndrome: benefits of vasodilating beta-blockers. Journal of clinical hypertension. 2011;13(1):52–9. doi: 10.1111/j.1751-7176.2010.00386.x 21214722.
32. Reisin E, Owen J. Treatment: special conditions. Metabolic syndrome: obesity and the hypertension connection. Journal of the American Society of Hypertension : JASH. 2015;9(2):156–9; quiz 60. doi: 10.1016/j.jash.2014.12.015 25748147.
33. Kveiborg B, Christiansen B, Major-Petersen A, Torp-Pedersen C. Metabolic effects of beta-adrenoceptor antagonists with special emphasis on carvedilol. American journal of cardiovascular drugs : drugs, devices, and other interventions. 2006;6(4):209–17. doi: 10.2165/00129784-200606040-00001 16913822.
34. Grassi G, Esler M. How to assess sympathetic activity in humans. J Hypertens. 1999;17(6):719–34. Epub 1999/08/25. doi: 10.1097/00004872-199917060-00001 10459867.
35. Feuerstein GZ, Ruffolo RR Jr. Carvedilol, a novel multiple action antihypertensive agent with antioxidant activity and the potential for myocardial and vascular protection. Eur Heart J. 1995;16 Suppl F:38–42. Epub 1995/07/01. doi: 10.1093/eurheartj/16.suppl_f.38 8521883.
36. Stoschitzky K, Koshucharova G, Zweiker R, Maier R, Watzinger N, Fruhwald FM, et al. Differing beta-blocking effects of carvedilol and metoprolol. Eur J Heart Fail. 2001;3(3):343–9. Epub 2001/05/30. doi: 10.1016/s1388-9842(01)00126-x 11378006.
37. Kinyua AW, Ko CM, Doan KV, Yang DJ, Huynh MKQ, Moh SH, et al. 4-hydroxy-3-methoxycinnamic acid regulates orexigenic peptides and hepatic glucose homeostasis through phosphorylation of FoxO1. Exp Mol Med. 2018;50(2):e437. Epub 2018/02/03. doi: 10.1038/emm.2017.253 29391540; PubMed Central PMCID: PMC5903816.
38. Boomsma F, Alberts G, van Eijk L, Man in 't Veld AJ, Schalekamp MA. Optimal collection and storage conditions for catecholamine measurements in human plasma and urine. Clinical chemistry. 1993;39(12):2503–8. 8252722.
39. Denfeld QE, Habecker BA, Woodward WR. Measurement of plasma norepinephrine and 3,4-dihydroxyphenylglycol: method development for a translational research study. BMC research notes. 2018;11(1):248. doi: 10.1186/s13104-018-3352-3 29673396; PubMed Central PMCID: PMC5909231.
40. Doan KV, Kinyua AW, Yang DJ, Ko CM, Moh SH, Shong KE, et al. FoxO1 in dopaminergic neurons regulates energy homeostasis and targets tyrosine hydroxylase. Nat Commun. 2016;7:12733. Epub 2016/09/30. doi: 10.1038/ncomms12733 27681312; PubMed Central PMCID: PMC5056402.
41. Mukaka MM. Statistics corner: A guide to appropriate use of correlation coefficient in medical research. Malawi Med J. 2012;24(3):69–71. Epub 2013/05/03. 23638278; PubMed Central PMCID: PMC3576830.
42. Woo AY, Xiao RP. beta-Adrenergic receptor subtype signaling in heart: from bench to bedside. Acta pharmacologica Sinica. 2012;33(3):335–41. doi: 10.1038/aps.2011.201 22286918; PubMed Central PMCID: PMC4077138.
43. Wang Q, Liu Y, Fu Q, Xu B, Zhang Y, Kim S, et al. Inhibiting Insulin-Mediated beta2-Adrenergic Receptor Activation Prevents Diabetes-Associated Cardiac Dysfunction. Circulation. 2017;135(1):73–88. doi: 10.1161/CIRCULATIONAHA.116.022281 27815373; PubMed Central PMCID: PMC5302024.
44. Seale P. Transcriptional Regulatory Circuits Controlling Brown Fat Development and Activation. Diabetes. 2015;64(7):2369–75. doi: 10.2337/db15-0203 26050669; PubMed Central PMCID: PMC4477361.
45. Snitker S, Macdonald I, Ravussin E, Astrup A. The sympathetic nervous system and obesity: role in aetiology and treatment. Obesity reviews : an official journal of the International Association for the Study of Obesity. 2000;1(1):5–15. doi: 10.1046/j.1467-789x.2000.00001.x 12119646.
46. Ahmad A. Carvedilol can Replace Insulin in the Treatment of Type 2 Diabetes Mellitus. Journal of Diabetes & Metabolism. 2017;8(2). doi: 10.4172/2155-6156.1000726
47. R NS, V A, B P, H LK, A MS, V HP, et al. The effect of carvedilol on blood glucose levels in normal albino rats. J Clin Diagn Res. 2013;7(9):1900–3. doi: 10.7860/JCDR/2013/6435.3346 24179893; PubMed Central PMCID: PMC3809632.
48. Schnabel P, Maack C, Mies F, Tyroller S, Scheer A, Bohm M. Binding properties of beta-blockers at recombinant beta1-, beta2-, and beta3-adrenoceptors. Journal of cardiovascular pharmacology. 2000;36(4):466–71. doi: 10.1097/00005344-200010000-00008 11026647.
Článok vyšiel v časopise
PLOS One
2019 Číslo 11
- Metamizol jako analgetikum první volby: kdy, pro koho, jak a proč?
- Nejasný stín na plicích – kazuistika
- Masturbační chování žen v ČR − dotazníková studie
- Úspěšná resuscitativní thorakotomie v přednemocniční neodkladné péči
- Dlouhodobá recidiva a komplikace spojené s elektivní operací břišní kýly
Najčítanejšie v tomto čísle
- A daily diary study on maladaptive daydreaming, mind wandering, and sleep disturbances: Examining within-person and between-persons relations
- A 3’ UTR SNP rs885863, a cis-eQTL for the circadian gene VIPR2 and lincRNA 689, is associated with opioid addiction
- A substitution mutation in a conserved domain of mammalian acetate-dependent acetyl CoA synthetase 2 results in destabilized protein and impaired HIF-2 signaling
- Molecular validation of clinical Pantoea isolates identified by MALDI-TOF