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Licensed Unlicensed Requires Authentication Published by De Gruyter October 21, 2015

Obesity-associated sympathetic overactivity in children and adolescents: the role of catecholamine resistance in lipid metabolism

Zhengtang Qi and Shuzhe Ding

Abstract

Background: Obesity in children and adolescents is characterized by chronic sympathetic overdrive and reduced epinephrine-stimulated lipolysis. This resistance to catecholamines occurs during the dynamic phase of fat accumulation. This review will focus on the relationship between sympathetic-adrenal activity and lipid metabolism, thereby highlighting the role of catecholamine resistance in the development of childhood obesity.

Results and conclusions: Catecholamine resistance causes lipid accumulation in adipose tissue by reducing lipolysis, increasing lipogenesis and impeding free fatty acid (FFA) transportation. Exercise improves catecholamine resistance, as evidenced by attenuated systemic sympathetic activity, reduced circulating catecholamine levels and enhanced β-adrenergic receptor signaling. Insulin resistance is mostly a casual result rather than a cause of childhood obesity. Therefore, catecholamine resistance in childhood obesity may promote insulin signaling in adipose tissue, thereby increasing lipogenesis. This review outlines a series of evidence for the role of catecholamine resistance as an upstream mechanism leading to childhood obesity.


Corresponding authors: Zhengtang Qi, PhD and Shuzhe Ding, PhD, College of Physical Education and Health, East China Normal University, 500 Dongchuan Road, 200241 Shanghai, P.R. China, Phone/Fax: +86-21-54345296, E-mail: (Zhengtang Qi), (Shuzhe Ding); and The Key Laboratory of Adolescent Health Assessment and Exercise Intervention, Ministry of Education, East China Normal University, Shanghai, P.R. China

Acknowledgments

This work was supported by grants from the National Natural Science Foundation of China (No. 31171142, 31300977), and the Key Laboratory Construction Project of Adolescent Health Assessment and Exercise Intervention of Ministry of Education, China (No. 40500-541235-14203/004).

Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.

Research funding: None declared.

Employment or leadership: None declared.

Honorarium: None declared.

Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.

References

1. Ziegler MG, Milic M, Sun P, Tang CM, Elayan H, et al. Endogenous epinephrine protects against obesity induced insulin resistance. Auton Neurosci 2011;162:32–4.10.1016/j.autneu.2011.01.009Search in Google Scholar PubMed PubMed Central

2. Lee ZS, Critchley JA, Tomlinson B, Young RP, Thomas GN, et al. Urinary epinephrine and norepinephrine interrelations with obesity, insulin, and the metabolic syndrome in Hong Kong Chinese. Metabolism 2001;50:135–43.10.1053/meta.2001.19502Search in Google Scholar PubMed

3. Zouhal H, Lemoine-Morel S, Mathieu ME, Casazza GA, Jabbour G. Catecholamines and obesity: effects of exercise and training. Sports Med 2013;43:591–600.10.1007/s40279-013-0039-8Search in Google Scholar PubMed

4. Collins S, Daniel KW, Petro AE, Surwit RS. Strain-specific response to beta 3-adrenergic receptor agonist treatment of diet-induced obesity in mice. Endocrinology 1997;138:405–13.10.1210/endo.138.1.4829Search in Google Scholar PubMed

5. Lambert EA, Straznicky NE, Lambert GW. A sympathetic view of human obesity. Clin Auton Res 2013;23:9–14.10.1007/s10286-012-0169-3Search in Google Scholar PubMed

6. Hall JE, da Silva AA, do Carmo JM, Dubinion J, Hamza S, et al. Obesity-induced hypertension: role of sympathetic nervous system, leptin, and melanocortins. J Biol Chem 2010;285:17271–6.10.1074/jbc.R110.113175Search in Google Scholar PubMed PubMed Central

7. Becton LJ, Shatat IF, Flynn JT. Hypertension and obesity: epidemiology, mechanisms and clinical approach. Indian J Pediatr 2012;79:1056–61.10.1007/s12098-012-0777-xSearch in Google Scholar PubMed

8. Bougneres P, Stunff CL, Pecqueur C, Pinglier E, Adnot P, et al. In vivo resistance of lipolysis to epinephrine. A new feature of childhood onset obesity. J Clin Invest 1997;99:2568–73.10.1172/JCI119444Search in Google Scholar PubMed PubMed Central

9. Carel JC, Le Stunff C, Condamine L, Mallet E, Chaussain JL, et al. Resistance to the lipolytic action of epinephrine: a new feature of protein Gs deficiency. J Clin Endocrinol Metab 1999;84:4127–31.10.1210/jcem.84.11.6145Search in Google Scholar PubMed

10. Wilson SM, Sato AF. Stress and paediatric obesity: what we know and where to go. Stress Health 2014;30:91–102.10.1002/smi.2501Search in Google Scholar PubMed

11. Holmes ME, Ekkekakis P, Eisenmann JC. The physical activity, stress and metabolic syndrome triangle: a guide to unfamiliar territory for the obesity researcher. Obes Rev 2010;11: 492–507.10.1111/j.1467-789X.2009.00680.xSearch in Google Scholar PubMed

12. Kuo LE, Czarnecka M, Kitlinska JB, Tilan JU, Kvetnansky R, et al. Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome. Ann N Y Acad Sci 2008;1148:232–7.10.1196/annals.1410.035Search in Google Scholar PubMed PubMed Central

13. Lin EJ, Sun M, Choi EY, Magee D, Stets CW, et al. Social overcrowding as a chronic stress model that increases adiposity in mice. Psychoneuroendocrino 2015;51:318–30.10.1016/j.psyneuen.2014.10.007Search in Google Scholar PubMed PubMed Central

14. Prior LJ, Davern PJ, Burke SL, Lim K, Armitage JA, et al. Exposure to a high-fat diet during development alters leptin and ghrelin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 2014;63:338–45.10.1161/HYPERTENSIONAHA.113.02498Search in Google Scholar PubMed

15. Prior LJ, Eikelis N, Armitage JA, Davern PJ, Burke SL, et al. Exposure to a high-fat diet alters leptin sensitivity and elevates renal sympathetic nerve activity and arterial pressure in rabbits. Hypertension 2010;55:862–U96.10.1161/HYPERTENSIONAHA.109.141119Search in Google Scholar PubMed

16. Lkhagvasuren B, Nakamura Y, Oka T, Sudo N, Nakamura K. Social defeat stress induces hyperthermia through activation of thermoregulatory sympathetic premotor neurons in the medullary raphe region. Eur J Neurosci 2011;34:1442–52.10.1111/j.1460-9568.2011.07863.xSearch in Google Scholar PubMed

17. Perez-Tejada J, Arregi A, Gomez-Lazaro E, Vegas O, Azpiroz A, et al. Coping with chronic social stress in mice: hypothalamic-pituitary-adrenal/sympathetic-adrenal-medullary axis activity, behavioral changes and effects of antalarmin treatment: implications for the study of stress-related psychopathologies. Neuroendocrinology 2013;98:73–88.10.1159/000353620Search in Google Scholar PubMed

18. Sloan EK, Capitanio JP, Tarara RP, Mendoza SP, Mason WA, et al. Social stress enhances sympathetic innervation of primate lymph nodes: mechanisms and implications for viral pathogenesis. J Neurosci 2007;27:8857–65.10.1523/JNEUROSCI.1247-07.2007Search in Google Scholar PubMed PubMed Central

19. Seals DR, Bell C. Chronic sympathetic activation: consequence and cause of age-associated obesity? Diabetes 2004;53:276–84.10.2337/diabetes.53.2.276Search in Google Scholar PubMed

20. Rahmouni K. Leptin-induced sympathetic nerve activation: signaling mechanisms and cardiovascular consequences in obesity. Curr Hypertens Rev 2010;6:104–209.10.2174/157340210791170994Search in Google Scholar PubMed PubMed Central

21. McDonald RB, Horwitz BA, Hamilton JS, Stern JS. Cold- and norepinephrine-induced thermogenesis in younger and older Fischer 344 rats. Am J Physiol 1988;254(3 Pt 2):R457–62.10.1152/ajpregu.1988.254.3.R457Search in Google Scholar PubMed

22. McDonald RB, Herrmann S, Curry DL. Norepinephrine sensitivity of the endocrine pancreas in aging F344 rats. Aging (Milano) 1992;4:227–30.10.1007/BF03324096Search in Google Scholar PubMed

23. Lambert GW, Straznicky NE, Lambert EA, Dixon JB, Schlaich MP. Sympathetic nervous activation in obesity and the metabolic syndrome–causes, consequences and therapeutic implications. Pharmacol Ther 2010;126:159–72.10.1016/j.pharmthera.2010.02.002Search in Google Scholar PubMed

24. Lambert EA, Rice T, Eikelis N, Straznicky NE, Lambert GW, et al. Sympathetic activity and markers of cardiovascular risk in nondiabetic severely obese patients: the effect of the initial 10% weight loss. Am J Hypertens 2014;27:1308–15.10.1093/ajh/hpu050Search in Google Scholar PubMed

25. Chen W, Leo S, Weng C, Yang X, Wu Y, et al. Mechanisms mediating renal sympathetic nerve activation in obesity-related hypertension. Herz 2015;40(Suppl 2):190–6.10.1007/s00059-014-4072-7Search in Google Scholar PubMed

26. Masuo K, Kawaguchi H, Mikami H, Ogihara T, Tuck ML. Serum uric acid and plasma norepinephrine concentrations predict subsequent weight gain and blood pressure elevation. Hypertension 2003;42:474–80.10.1161/01.HYP.0000091371.53502.D3Search in Google Scholar PubMed

27. Vaz M, Jennings G, Turner A, Cox H, Lambert G, et al. Regional sympathetic nervous activity and oxygen consumption in obese normotensive human subjects. Circulation 1997;96:3423–9.10.1161/01.CIR.96.10.3423Search in Google Scholar

28. Grassi G, Seravalle G, Brambilla G, Buzzi S, Volpe M, et al. Regional differences in sympathetic activation in lean and obese normotensive individuals with obstructive sleep apnoea. J Hypertens 2014;32:383–8.10.1097/HJH.0000000000000034Search in Google Scholar PubMed

29. Straznicky NE, Eikelis N, Lambert EA, Esler MD. Mediators of sympathetic activation in metabolic syndrome obesity. Curr Hypertens Rep 2008;10:440–7.10.1007/s11906-008-0083-1Search in Google Scholar PubMed

30. Hering D, Kucharska W, Kara T, Somers VK, Parati G, et al. Effects of acute and long-term slow breathing exercise on muscle sympathetic nerve activity in untreated male patients with hypertension. J Hypertens 2013;31:739–46.10.1097/HJH.0b013e32835eb2cfSearch in Google Scholar PubMed

31. Dulloo AG. Biomedicine. A sympathetic defense against obesity. Science 2002;297:780–1.10.1126/science.1074923Search in Google Scholar PubMed

32. Imai J, Katagiri H, Yamada T, Ishigaki Y, Ogihara T, et al. Cold exposure suppresses serum adiponectin levels through sympathetic nerve activation in mice. Obesity 2006;14:1132–41.10.1038/oby.2006.130Search in Google Scholar PubMed

33. Xiang LS, Lu SL, Mittwede PN, Clemmer JS, Husband GW, et al. Beta(2)-Adrenoreceptor blockade improves early posttrauma hyperglycemia and pulmonary injury in obese rats. Am J Physiol-Heart C 2014;307:H621–H7.10.1152/ajpheart.00208.2014Search in Google Scholar PubMed PubMed Central

34. Assadi F. The growing epidemic of hypertension among children and adolescents: a challenging road ahead. Pediatr Cardiol 2012;33:1013–20.10.1007/s00246-012-0333-5Search in Google Scholar PubMed

35. Lee P, Kengne AP, Greenfield JR, Day RO, Chalmers J, et al. Metabolic sequelae of beta-blocker therapy: weighing in on the obesity epidemic? Int J Obesity 2011;35:1395–403.10.1038/ijo.2010.284Search in Google Scholar PubMed

36. Deedwania P. Hypertension, dyslipidemia, and insulin resistance in patients with diabetes mellitus or the cardiometabolic syndrome: benefits of vasodilating beta-blockers. J Clin Hypertens 2011;13:52–9.10.1111/j.1751-7176.2010.00386.xSearch in Google Scholar PubMed PubMed Central

37. Eyre EL, Duncan MJ, Birch SL, Fisher JP. The influence of age and weight status on cardiac autonomic control in healthy children: a review. Auton Neurosci-Basic 2014;186:8–21.10.1016/j.autneu.2014.09.019Search in Google Scholar PubMed

38. Graziano PA, Calkins SD, Keane SP, O’Brien M. Cardiovascular regulation profile predicts developmental trajectory of BMI and pediatric obesity. Obesity 2011;19:1818–25.10.1038/oby.2011.98Search in Google Scholar PubMed PubMed Central

39. Kaufman CL, Kaiser DR, Steinberger J, Kelly AS, Dengel DR. Relationships of cardiac autonomic function with metabolic abnormalities in childhood obesity. Obesity 2007;15:1164–71.10.1038/oby.2007.619Search in Google Scholar PubMed

40. de Faria AP, Modolo R, Fontana V, Moreno H. Adipokines: novel players in resistant hypertension. J Clin Hypertens (Greenwich) 2014;16:754–9.10.1111/jch.12399Search in Google Scholar PubMed PubMed Central

41. Ohashi K, Shibata R, Murohara T, Ouchi N. Role of anti-inflammatory adipokines in obesity-related diseases. Trends Endocrinol Metab 2014;25:348–55.10.1016/j.tem.2014.03.009Search in Google Scholar PubMed

42. Sayin O, Tokgoz Y, Arslan N. Investigation of adropin and leptin levels in pediatric obesity-related nonalcoholic fatty liver disease. J Pediatr Endocrinol Metab 2014;27:479–84.10.1515/jpem-2013-0296Search in Google Scholar PubMed

43. Nishimura R, Sano H, Matsudaira T, Miyashita Y, Morimoto A, et al. Childhood obesity and its relation to serum adiponectin and leptin: a report from a population-based study. Diabetes Res Clin Pract 2007;76:245–50.10.1016/j.diabres.2006.09.023Search in Google Scholar PubMed

44. Simonds SE, Cowley MA, Enriori PJ. Leptin increasing sympathetic nerve outflow in obesity: a cure for obesity or a potential contributor to metabolic syndrome? Adipocyte 2012;1:177–81.10.4161/adip.20690Search in Google Scholar PubMed PubMed Central

45. Morgan DA, Thedens DR, Weiss R, Rahmouni K. Mechanisms mediating renal sympathetic activation to leptin in obesity. Am J Physiol Regul Integr Comp Physiol 2008;295:R1730–6.10.1152/ajpregu.90324.2008Search in Google Scholar PubMed PubMed Central

46. Shi Z, Brooks VL. Leptin differentially increases sympathetic nerve activity and its baroreflex regulation in female rats: role of oestrogen. J Physiol 2015;593:1633–47.10.1113/jphysiol.2014.284638Search in Google Scholar PubMed PubMed Central

47. Ortega L, Riestra P, Navarro P, Gavela-Perez T, Soriano-Guillen L, et al. Resistin levels are related to fat mass, but not to body mass index in children. Peptides 2013;49:49–52.10.1016/j.peptides.2013.08.019Search in Google Scholar PubMed

48. Chen XY, Zhang JH, Liu F, Liu HM, Song YY, et al. Association of serum resistin levels with metabolic syndrome and early atherosclerosis in obese Chinese children. J Pediatr Endocrinol Metab 2013;26:855–60.10.1515/jpem-2012-0326Search in Google Scholar PubMed

49. Kosari S, Rathner JA, Badoer E. Central resistin enhances renal sympathetic nerve activity via phosphatidylinositol 3-kinase but reduces the activity to brown adipose tissue via extracellular signal-regulated kinase 1/2. J Neuroendocrinol 2012;24:1432–9.10.1111/j.1365-2826.2012.02352.xSearch in Google Scholar PubMed

50. Kosari S, Rathner JA, Chen F, Kosari S, Badoer E. Centrally administered resistin enhances sympathetic nerve activity to the hindlimb but attenuates the activity to brown adipose tissue. Endocrinology 2011;152:2626–33.10.1210/en.2010-1492Search in Google Scholar PubMed

51. Haider DG, Holzer G, Schaller G, Weghuber D, Widhalm K, et al. The adipokine visfatin is markedly elevated in obese children. J Pediatr Gastroenterol Nutr 2006;43:548–9.10.1097/01.mpg.0000235749.50820.b3Search in Google Scholar PubMed

52. Ooi SQ, Chan RM, Poh LK, Loke KY, Heng CK, et al. Visfatin and its genetic variants are associated with obesity-related morbidities and cardiometabolic risk in severely obese children. Pediatr Obes 2014;9:81–91.10.1111/j.2047-6310.2013.00149.xSearch in Google Scholar PubMed

53. Martos-Moreno GA, Kratzsch J, Korner A, Barrios V, Hawkins F, et al. Serum visfatin and vaspin levels in prepubertal children: effect of obesity and weight loss after behavior modifications on their secretion and relationship with glucose metabolism. Int J Obes (Lond) 2011;35:1355–62.10.1038/ijo.2010.280Search in Google Scholar PubMed

54. Jamurtas A, Stavropoulos-Kalinoglou A, Koutsias S, Koutedakis Y, Fatouros I. Adiponectin, resistin and visfatin in childhood obesity and exercise. Pediatr Exerc Sci 2015 [Epub ahead of print].10.1123/pes.2014-0072Search in Google Scholar PubMed

55. Tanida M, Shen J, Horii Y, Matsuda M, Kihara S, et al. Effects of adiponectin on the renal sympathetic nerve activity and blood pressure in rats. Exp Biol Med (Maywood) 2007;232:390–7.Search in Google Scholar

56. Yamauchi T, Kamon J, Waki H, Terauchi Y, Kubota N, et al. The fat-derived hormone adiponectin reverses insulin resistance associated with both lipoatrophy and obesity. Nat Med 2001;7:941–6.10.1038/90984Search in Google Scholar PubMed

57. Ohashi K, Kihara S, Ouchi N, Kumada M, Fujita K, et al. Adiponectin replenishment ameliorates obesity-related hypertension. Hypertension 2006;47:1108–16.10.1161/01.HYP.0000222368.43759.a1Search in Google Scholar PubMed

58. Surwit RS, Dixon TM, Petro AE, Daniel KW, Collins S. Diazoxide restores beta3-adrenergic receptor function in diet-induced obesity and diabetes. Endocrinology 2000;141:3630–7.10.1210/endo.141.10.7726Search in Google Scholar PubMed

59. McAllan L, Skuse P, Cotter PD, O’Connor P, Cryan JF, et al. Protein quality and the protein to carbohydrate ratio within a high fat diet influences energy balance and the gut microbiota In C57BL/6J mice. PLoS One 2014;9:e88904.10.1371/journal.pone.0088904Search in Google Scholar PubMed PubMed Central

60. Aparecida de Franca S, Pavani Dos Santos M, Nunes Queiroz da Costa RV, Froelich M, Buzelle SL, et al. Low-protein, high-carbohydrate diet increases glucose uptake and fatty acid synthesis in brown adipose tissue of rats. Nutrition 2014;30:473–80.10.1016/j.nut.2013.10.004Search in Google Scholar PubMed

61. Yang L, Lu K, Wen XY, Liu H, Chen AP, et al. Jueming Prescription reduces body weight by increasing the mRNA expressions of beta3-adrenergic receptor and uncoupling protein-2 in adipose tissue of diet-induced obese rats. Chin J Integr Med 2012;18:775–81.10.1007/s11655-011-0959-9Search in Google Scholar PubMed

62. Bartolomucci A, La Corte G, Possenti R, Locatelli V, Rigamonti AE, et al. TLQP-21, a VGF-derived peptide, increases energy expenditure and prevents the early phase of diet-induced obesity. Proc Natl Acad Sci USA 2006;103:14584–9.10.1073/pnas.0606102103Search in Google Scholar

63. Huang X, Charbeneau RA, Fu Y, Kaur K, Gerin I, et al. Resistance to diet-induced obesity and improved insulin sensitivity in mice with a regulator of G protein signaling-insensitive G184S Gnai2 allele. Diabetes 2008;57:77–85.10.2337/db07-0599Search in Google Scholar

64. Kaartinen JM, LaNoue KF, Martin LF, Vikman HL, Ohisalo JJ. Beta-adrenergic responsiveness of adenylate cyclase in human adipocyte plasma membranes in obesity and after massive weight reduction. Metabolism 1995;44:1288–92.10.1016/0026-0495(95)90031-4Search in Google Scholar

65. Wang Z, Li V, Chan GC, Phan T, Nudelman AS, et al. Adult type 3 adenylyl cyclase-deficient mice are obese. PLoS One 2009;4:e6979.10.1371/journal.pone.0006979Search in Google Scholar

66. Nissim I, Horyn O, Daikhin Y, Chen P, Li C, et al. The molecular and metabolic influence of long term agmatine consumption. J Biol Chem 2014;289:9710–29.10.1074/jbc.M113.544726Search in Google Scholar

67. Illiano G, Naviglio S, Pagano M, Spina A, Chiosi E, et al. Leptin affects adenylate cyclase activity in H9c2 cardiac cell line: effects of short- and long-term exposure. Am J Hypertens 2002;15(7 Pt 1):638–43.10.1016/S0895-7061(02)02925-4Search in Google Scholar

68. Fruhbeck G, Gomez-Ambrosi J. Modulation of the leptin-induced white adipose tissue lipolysis by nitric oxide. Cell Signal 2001;13:827–33.10.1016/S0898-6568(01)00211-XSearch in Google Scholar

69. Nakra N, Bhargava S, Dzuira J, Caprio S, Bazzy-Asaad A. Sleep-disordered breathing in children with metabolic syndrome: the role of leptin and sympathetic nervous system activity and the effect of continuous positive airway pressure. Pediatrics 2008;122:e634–42.10.1542/peds.2008-0154Search in Google Scholar PubMed PubMed Central

70. Adigun AA, Wrench N, Levin ED, Seidler FJ, Slotkin TA. Neonatal parathion exposure and interactions with a high-fat diet in adulthood: adenylyl cyclase-mediated cell signaling in heart, liver and cerebellum. Brain Res Bull 2010;81:605–12.10.1016/j.brainresbull.2010.01.003Search in Google Scholar PubMed PubMed Central

71. London E, Rothenbuhler A, Lodish M, Gourgari E, Keil M, et al. Differences in adiposity in Cushing syndrome caused by PRKAR1A mutations: clues for the role of cyclic AMP signaling in obesity and diagnostic implications. J Clin Endocrinol Metab 2014;99:E303–10.10.1210/jc.2013-1956Search in Google Scholar PubMed PubMed Central

72. London E, Nesterova M, Sinaii N, Szarek E, Chanturiya T, et al. Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIalpha. Endocrinology 2014;155:3397–408.10.1210/en.2014-1122Search in Google Scholar

73. Czyzyk TA, Sikorski MA, Yang L, McKnight GS. Disruption of the RIIbeta subunit of PKA reverses the obesity syndrome of Agouti lethal yellow mice. Proc Natl Acad Sci USA 2008;105:276–81.10.1073/pnas.0710607105Search in Google Scholar

74. Kou XH, Zhu MF, Chen D, Lu Y, Song HZ, et al. Bilobetin ameliorates insulin resistance by PKA-mediated phosphorylation of PPARalpha in rats fed a high-fat diet. Br J Pharmacol 2012;165:2692–706.10.1111/j.1476-5381.2011.01727.xSearch in Google Scholar

75. Badin PM, Vila IK, Louche K, Mairal A, Marques MA, et al. High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle. Endocrinology 2013;154:1444–53.10.1210/en.2012-2029Search in Google Scholar

76. Gaidhu MP, Anthony NM, Patel P, Hawke TJ, Ceddia RB. Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. Am J Physiol Cell Physiol 2010;298:C961–71.10.1152/ajpcell.00547.2009Search in Google Scholar

77. Khoo JC, Jarett L, Mayer SE, Steinberg D. Subcellular distribution of and epinephrine-induced changes in hormone-sensitive lipase, phosphorylase, and phosphorylase kinase in rat adipocytes. J Biol Chem 1972;247:4812–8.10.1016/S0021-9258(19)44983-1Search in Google Scholar

78. Prats C, Donsmark M, Qvortrup K, Londos C, Sztalryd C, et al. Decrease in intramuscular lipid droplets and translocation of HSL in response to muscle contraction and epinephrine. J Lipid Res 2006;47:2392–9.10.1194/jlr.M600247-JLR200Search in Google Scholar PubMed

79. Lampidonis AD, Rogdakis E, Voutsinas GE, Stravopodis DJ. The resurgence of Hormone-Sensitive Lipase (HSL) in mammalian lipolysis. Gene 2011;477:1–11.10.1016/j.gene.2011.01.007Search in Google Scholar PubMed

80. Patel S, Yang W, Kozusko K, Saudek V, Savage DB. Perilipins 2 and 3 lack a carboxy-terminal domain present in perilipin 1 involved in sequestering ABHD5 and suppressing basal lipolysis. Proc Natl Acad Sci USA 2014;111:9163–8.10.1073/pnas.1318791111Search in Google Scholar PubMed PubMed Central

81. Kern PA, Di Gregorio G, Lu T, Rassouli N, Ranganathan G. Perilipin expression in human adipose tissue is elevated with obesity. J Clin Endocrinol Metab 2004;89:1352–8.10.1210/jc.2003-031388Search in Google Scholar PubMed

82. Rinnankoski-Tuikka R, Hulmi JJ, Torvinen S, Silvennoinen M, Lehti M, et al. Lipid droplet-associated proteins in high-fat fed mice with the effects of voluntary running and diet change. Metabolism 2014;63:1031–40.10.1016/j.metabol.2014.05.010Search in Google Scholar PubMed

83. Miyoshi H, Souza SC, Endo M, Sawada T, Perfield JW, 2nd, et al. Perilipin overexpression in mice protects against diet-induced obesity. J Lipid Res 2010;51:975–82.10.1194/jlr.M002352Search in Google Scholar PubMed PubMed Central

84. Abu-Elheiga L, Oh W, Kordari P, Wakil SJ. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets. Proc Natl Acad Sci USA 2003;100:10207–12.10.1073/pnas.1733877100Search in Google Scholar PubMed PubMed Central

85. Abu-Elheiga L, Wu H, Gu Z, Bressler R, Wakil SJ. Acetyl-CoA carboxylase 2-/- mutant mice are protected against fatty liver under high-fat, high-carbohydrate dietary and de novo lipogenic conditions. J Biol Chem 2012;287:12578–88.10.1074/jbc.M111.309559Search in Google Scholar PubMed PubMed Central

86. Hattori A, Mawatari K, Tsuzuki S, Yoshioka E, Toda S, et al. Beta-adrenergic-AMPK pathway phosphorylates acetyl-CoA carboxylase in a high-epinephrine rat model, SPORTS. Obesity (Silver Spring) 2010;18:48–54.10.1038/oby.2009.145Search in Google Scholar PubMed

87. Konstandi M, Shah YM, Matsubara T, Gonzalez FJ. Role of PPARalpha and HNF4alpha in stress-mediated alterations in lipid homeostasis. PLoS One 2013;8:e70675.10.1371/journal.pone.0070675Search in Google Scholar PubMed PubMed Central

88. Herzig S, Long F, Jhala US, Hedrick S, Quinn R, et al. CREB regulates hepatic gluconeogenesis through the coactivator PGC-1. Nature 2001;413:179–83.10.1038/35093131Search in Google Scholar PubMed

89. Herzig S, Hedrick S, Morantte I, Koo SH, Galimi F, et al. CREB controls hepatic lipid metabolism through nuclear hormone receptor PPAR-gamma. Nature 2003;426:190–3.10.1038/nature02110Search in Google Scholar PubMed

90. Fujimori K, Yano M, Miyake H, Kimura H. Termination mechanism of CREB-dependent activation of COX-2 expression in early phase of adipogenesis. Mol Cell Endocrinol 2014;384:12–22.10.1016/j.mce.2013.12.014Search in Google Scholar PubMed

91. Bocarsly ME, Avena NM. A high-fat diet or galanin in the PVN decreases phosphorylation of CREB in the nucleus accumbens. Neuroscience 2013;248C:61–6.10.1016/j.neuroscience.2013.05.046Search in Google Scholar PubMed PubMed Central

92. Morris KA, Gold PE. Epinephrine and glucose modulate training-related CREB phosphorylation in old rats: relationships to age-related memory impairments. Exp Gerontol 2013;48:115–27.10.1016/j.exger.2012.11.010Search in Google Scholar PubMed PubMed Central

93. Jocken JW, Roepstorff C, Goossens GH, van der Baan P, van Baak M, et al. Hormone-sensitive lipase serine phosphorylation and glycerol exchange across skeletal muscle in lean and obese subjects: effect of beta-adrenergic stimulation. Diabetes 2008;57:1834–41.10.2337/db07-0857Search in Google Scholar PubMed PubMed Central

94. Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 2012;287:11968–80.10.1074/jbc.M111.336834Search in Google Scholar PubMed PubMed Central

95. Jost P, Fasshauer M, Kahn CR, Benito M, Meyer M, et al. Atypical beta-adrenergic effects on insulin signaling and action in beta(3)-adrenoceptor-deficient brown adipocytes. Am J Physiol Endocrinol Metab 2002;283:E146–53.10.1152/ajpendo.00531.2001Search in Google Scholar PubMed

96. Cahova M, Palenickova E, Papackova Z, Dankova H, Skop V, et al. Epinephrine-dependent control of glucose metabolism in white adipose tissue: the role of alpha- and beta-adrenergic signalling. Exp Biol Med (Maywood) 2012;237:211–8.10.1258/ebm.2011.011189Search in Google Scholar PubMed

97. Hunzicker-Dunn ME, Lopez-Biladeau B, Law NC, Fiedler SE, Carr DW, et al. PKA and GAB2 play central roles in the FSH signaling pathway to PI3K and AKT in ovarian granulosa cells. Proc Natl Acad Sci USA 2012;109:E2979–88.10.1073/pnas.1205661109Search in Google Scholar PubMed PubMed Central

98. Frier BC, Jacobs RL, Wright DC. Interactions between the consumption of a high-fat diet and fasting in the regulation of fatty acid oxidation enzyme gene expression: an evaluation of potential mechanisms. Am J Physiol Regul Integr Comp Physiol 2011;300:R212–21.10.1152/ajpregu.00367.2010Search in Google Scholar PubMed

99. Cortes VA, Curtis DE, Sukumaran S, Shao X, Parameswara V, et al. Molecular mechanisms of hepatic steatosis and insulin resistance in the AGPAT2-deficient mouse model of congenital generalized lipodystrophy. Cell Metab 2009;9:165–76.10.1016/j.cmet.2009.01.002Search in Google Scholar PubMed PubMed Central

100. Wang F, Mullican SE, DiSpirito JR, Peed LC, Lazar MA. Lipoatrophy and severe metabolic disturbance in mice with fat-specific deletion of PPARgamma. Proc Natl Acad Sci USA 2013;110:18656–61.10.1073/pnas.1314863110Search in Google Scholar PubMed PubMed Central

101. Myers MG, Jr, Leibel RL, Seeley RJ, Schwartz MW. Obesity and leptin resistance: distinguishing cause from effect. Trends Endocrinol Metab 2010;21:643–51.10.1016/j.tem.2010.08.002Search in Google Scholar PubMed PubMed Central

102. Berbari NF, Pasek RC, Malarkey EB, Yazdi SM, McNair AD, et al. Leptin resistance is a secondary consequence of the obesity in ciliopathy mutant mice. Proc Natl Acad Sci USA 2013;110:7796–801.10.1073/pnas.1210192110Search in Google Scholar PubMed PubMed Central

103. van Greevenbroek MM, Ghosh S, van der Kallen CJ, Brouwers MC, Schalkwijk CG, et al. Up-regulation of the complement system in subcutaneous adipocytes from nonobese, hypertriglyceridemic subjects is associated with adipocyte insulin resistance. J Clin Endocrinol Metab 2012;97:4742–52.10.1210/jc.2012-2539Search in Google Scholar PubMed PubMed Central

104. Bessey PQ, Brooks DC, Black PR, Aoki TT, Wilmore DW. Epinephrine acutely mediates skeletal muscle insulin resistance. Surgery 1983;94:172–9.Search in Google Scholar

105. Deibert DC, DeFronzo RA. Epinephrine-induced insulin resistance in man. J Clin Invest 1980;65:717–21.10.1172/JCI109718Search in Google Scholar PubMed PubMed Central

106. Scherer T, O’Hare J, Diggs-Andrews K, Schweiger M, Cheng B, et al. Brain insulin controls adipose tissue lipolysis and lipogenesis. Cell Metab 2011;13:183–94.10.1016/j.cmet.2011.01.008Search in Google Scholar PubMed PubMed Central

107. Kawashita NH, Moura MA, Brito MN, Brito SM, Garofalo MA, et al. Relative importance of sympathetic outflow and insulin in the reactivation of brown adipose tissue lipogenesis in rats adapted to a high-protein diet. Metabolism 2002;51:343–9.10.1053/meta.2002.29967Search in Google Scholar PubMed

108. Marion V, Mockel A, De Melo C, Obringer C, Claussmann A, et al. BBS-induced ciliary defect enhances adipogenesis, causing paradoxical higher-insulin sensitivity, glucose usage, and decreased inflammatory response. Cell Metab 2012;16:363–77.10.1016/j.cmet.2012.08.005Search in Google Scholar PubMed

109. Chutkow WA, Birkenfeld AL, Brown JD, Lee HY, Frederick DW, et al. Deletion of the alpha-arrestin protein Txnip in mice promotes adiposity and adipogenesis while preserving insulin sensitivity. Diabetes 2010;59:1424–34.10.2337/db09-1212Search in Google Scholar PubMed PubMed Central

110. Stener-Victorin E, Jedel E, Janson PO, Sverrisdottir YB. Low-frequency electroacupuncture and physical exercise decrease high muscle sympathetic nerve activity in polycystic ovary syndrome. Am J Physiol Regul Integr Comp Physiol 2009;297:R387–95.10.1152/ajpregu.00197.2009Search in Google Scholar PubMed

111. Rengo G, Leosco D, Zincarelli C, Marchese M, Corbi G, et al. Adrenal GRK2 lowering is an underlying mechanism for the beneficial sympathetic effects of exercise training in heart failure. Am J Physiol Heart Circ Physiol 2010;298:H2032–8.10.1152/ajpheart.00702.2009Search in Google Scholar PubMed

112. Groehs RV, Toschi-Dias E, Antunes-Correa LM, Trevizan PF, Rondon MU, et al. Exercise training prevents the deterioration in the arterial baroreflex control of sympathetic nerve activity in chronic heart failure patients. Am J Physiol-Heart C 2015;308:H1096–H102.10.1152/ajpheart.00723.2014Search in Google Scholar PubMed PubMed Central

113. Chen T, Cai MX, Li YY, He ZX, Shi XC, et al. Aerobic exercise inhibits sympathetic nerve sprouting and restores beta-adrenergic receptor balance in rats with myocardial infarction. PLoS One 2014;9:e97810.10.1371/journal.pone.0097810Search in Google Scholar PubMed PubMed Central

114. Stephenson EJ, Lessard SJ, Rivas DA, Watt MJ, Yaspelkis BB, 3rd, et al. Exercise training enhances white adipose tissue metabolism in rats selectively bred for low- or high-endurance running capacity. Am J Physiol Endocrinol Metab 2013;305:E429–38.10.1152/ajpendo.00544.2012Search in Google Scholar PubMed PubMed Central

115. Petridou A, Tsalouhidou S, Tsalis G, Schulz T, Michna H, et al. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue. Metabolism 2007;56:1029–36.10.1016/j.metabol.2007.03.011Search in Google Scholar PubMed

116. Takekoshi K, Fukuhara M, Quin Z, Nissato S, Isobe K, et al. Long-term exercise stimulates adenosine monophosphate-activated protein kinase activity and subunit expression in rat visceral adipose tissue and liver. Metabolism 2006;55:1122–8.10.1016/j.metabol.2006.04.007Search in Google Scholar PubMed

117. Palacios OM, Carmona JJ, Michan S, Chen KY, Manabe Y, et al. Diet and exercise signals regulate SIRT3 and activate AMPK and PGC-1alpha in skeletal muscle. Aging (Albany NY) 2009;1:771–83.10.18632/aging.100075Search in Google Scholar PubMed PubMed Central

118. Marion-Latard F, De Glisezinski I, Crampes F, Berlan M, Galitzky J, et al. A single bout of exercise induces beta-adrenergic desensitization in human adipose tissue. Am J Physiol Regul Integr Comp Physiol 2001;280:R166–73.10.1152/ajpregu.2001.280.1.R166Search in Google Scholar PubMed

119. Stich V, Marion-Latard F, Hejnova J, Viguerie N, Lefort C, et al. Hypocaloric diet reduces exercise-induced alpha 2-adrenergic antilipolytic effect and alpha 2-adrenergic receptor mRNA levels in adipose tissue of obese women. J Clin Endocrinol Metab 2002;87:1274–81.Search in Google Scholar

120. Stich V, De Glisezinski I, Crampes F, Hejnova J, Cottet-Emard JM, et al. Activation of alpha(2)-adrenergic receptors impairs exercise-induced lipolysis in SCAT of obese subjects. Am J Physiol Regul Integr Comp Physiol 2000;279:R499–504.10.1152/ajpregu.2000.279.2.R499Search in Google Scholar PubMed

121. Richterova B, Stich V, Moro C, Polak J, Klimcakova E, et al. Effect of endurance training on adrenergic control of lipolysis in adipose tissue of obese women. J Clin Endocrinol Metab 2004;89:1325–31.10.1210/jc.2003-031001Search in Google Scholar PubMed

122. Morrison C. Interaction between exercise and leptin in the treatment of obesity. Diabetes 2008;57:534–5.10.2337/db08-0007Search in Google Scholar PubMed

123. Seo DI, So WY, Ha S, Yoo EJ, Kim D, et al. Effects of 12 weeks of combined exercise training on visfatin and metabolic syndrome factors in obese middle-aged women. J Sports Sci Med 2011;10:222–6.Search in Google Scholar

124. Cassaglia PA, Hermes SM, Aicher SA, Brooks VL. Insulin acts in the arcuate nucleus to increase lumbar sympathetic nerve activity and baroreflex function in rats. J Physiol 2011;589(Pt 7):1643–62.10.1113/jphysiol.2011.205575Search in Google Scholar PubMed PubMed Central

125. Monahan KD, Wilson TE, Ray CA. Omega-3 fatty acid supplementation augments sympathetic nerve activity responses to physiological stressors in humans. Hypertension 2004;44:732–8.10.1161/01.HYP.0000145292.38579.f4Search in Google Scholar PubMed

Received: 2015-5-2
Accepted: 2015-8-27
Published Online: 2015-10-21
Published in Print: 2016-2-1

©2016 by De Gruyter

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