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Environmental Manipulation and Neuropeptide Effects on Energy Balance and Cancer

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Murine Models, Energy Balance, and Cancer

Part of the book series: Energy Balance and Cancer ((EBAC,volume 10))

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Abstract

Social and environmental factors have profound impacts on energy balance and cancer. Yet many experimental studies of the metabolic syndromes and cancer utilize animals in laboratory conditions without adequate social interactions. We recently demonstrate that environments that are more complex and challenging, but not stressful per se, have robust effects on body composition, energy balance, and peripheral cancer progression. One key underlying mechanism is the activation of a specific neuroendocrine brain-adipocyte axis, the hypothalamic-sympathoneural-adipocyte (HSA) axis . The social, physical, and cognitive stimuli provided by the enriched environments induce brain-derived neurotrophic factor (BDNF) in the hypothalamus and the ensuing sympathetic innervation of adipose tissue. The remodeling of the adipose tissue, including the white-to-brown phenotypic switch and the suppression of leptin, leads to antiobesity and anticancer phenotype. This chapter summarizes this work and discusses how environmental enrichment (EE) can serve as a valuable animal model to study eustress (positive or benign stress), metabolism, cancer, and aging.

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References

  1. Cao L, During MJ. What is the brain-cancer connection? Ann Rev Neurosci. 2012;35:331–45.

    CAS  PubMed  Google Scholar 

  2. Nithianantharajah J, Hannan AJ. Enriched environments, experience-dependent plasticity and disorders of the nervous system. Nat Rev Neurosci. 2006;7(9):697–709.

    CAS  PubMed  Google Scholar 

  3. Kolonel LN, Altshuler D, Henderson BE. The multiethnic cohort study: exploring genes, lifestyle and cancer risk. Nat Rev Cancer. 2004;4(7):519–27.

    CAS  PubMed  Google Scholar 

  4. Baade PD, Youlden DR, Krnjacki LJ. International epidemiology of prostate cancer: geographical distribution and secular trends. Mol Nutr Food Res. 2009;53(2):171–84.

    CAS  PubMed  Google Scholar 

  5. McAllister SS, Weinberg RA. Tumor-host interactions: a far-reaching relationship. J Clin Oncol. 2010;28(26):4022–8.

    PubMed  Google Scholar 

  6. Green McDonald P, O’Connell M, Lutgendorf SK. Psychoneuroimmunology and cancer: a decade of discovery, paradigm shifts, and methodological innovations. Brain Behav Immun. 2013;30 Suppl:S1–9.

    PubMed  Google Scholar 

  7. Hanahan D, Weinberg RA. The hallmarks of cancer. Cell. 2000;100(1):57–70.

    CAS  PubMed  Google Scholar 

  8. Aaronson SA. Growth factors and cancer. Science. 1991;254(5035):1146–53.

    CAS  PubMed  Google Scholar 

  9. Darnell RB, Posner JB. Paraneoplastic syndromes affecting the nervous system. Semin Oncol. 2006;33(3):270–98.

    PubMed  Google Scholar 

  10. Castano Z, Tracy K, McAllister SS. The tumor macroenvironment and systemic regulation of breast cancer progression. Int J Dev Biol. 2011;55(7–9):889–97.

    PubMed  Google Scholar 

  11. Young D, Lawlor PA, Leone P, Dragunow M, During MJ. Environmental enrichment inhibits spontaneous apoptosis, prevents seizures and is neuroprotective. Nat Med. 1999;5(4):448–53.

    CAS  PubMed  Google Scholar 

  12. Cao L, et al. VEGF links hippocampal activity with neurogenesis, learning and memory. Nat Genet. 2004;36(8):827–35.

    CAS  PubMed  Google Scholar 

  13. Cao L, et al. Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell. 2010;142(1):52–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  14. Bessesen DH. Regulation of body weight: what is the regulated parameter? Physiol Behav. 2011;104:599–607.

    CAS  PubMed  Google Scholar 

  15. van Dijk G, Buwalda B. Neurobiology of the metabolic syndrome: an allostatic perspective. Eur J Pharmacol. 2008;585(1):137–46.

    PubMed  Google Scholar 

  16. Bjorntorp P. Abdominal obesity and the metabolic syndrome. Ann Med. 1992;24(6):465–8.

    CAS  PubMed  Google Scholar 

  17. Brunner EJ, et al. Adrenocortical, autonomic, and inflammatory causes of the metabolic syndrome: nested case-control study. Circulation. 2002;106(21):2659–65.

    CAS  PubMed  Google Scholar 

  18. Frontini A, Cinti S. Distribution and development of brown adipocytes in the murine and human adipose organ. Cell Metab. 2010;11(4):253–6.

    CAS  PubMed  Google Scholar 

  19. Himms-Hagen J, et al. Multilocular fat cells in WAT of CL-316243-treated rats derive directly from white adipocytes. Am J Physiol Cell Physiol. 2000;279(3):C670–81.

    CAS  PubMed  Google Scholar 

  20. Granneman JG, Li P, Zhu Z, Lu Y. Metabolic and cellular plasticity in white adipose tissue I: effects of beta3-adrenergic receptor activation. Am J Physiol Endocrinol Metab. 2005;289(4):E608–16.

    CAS  PubMed  Google Scholar 

  21. Murano I, Barbatelli G, Giordano A, Cinti S. Noradrenergic parenchymal nerve fiber branching after cold acclimatisation correlates with brown adipocyte density in mouse adipose organ. J Anat. 2009;214(1):171–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  22. Ravussin E, Kozak LP. Have we entered the brown adipose tissue renaissance? Obes Rev. 2009;10(3):265–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  23. Gesta S, Tseng YH, Kahn CR. Developmental origin of fat: tracking obesity to its source. Cell. 2007;131(2):242–56.

    CAS  PubMed  Google Scholar 

  24. Petrovic N, et al. Chronic peroxisome proliferator-activated receptor gamma (PPARgamma) activation of epididymally derived white adipocyte cultures reveals a population of thermogenically competent, UCP1-containing adipocytes molecularly distinct from classic brown adipocytes. J Biol Chem. 2010;285(10):7153–64.

    CAS  PubMed Central  PubMed  Google Scholar 

  25. Cypess AM, et al. Identification and importance of brown adipose tissue in adult humans. N Engl J Med. 2009;360(15):1509–17.

    CAS  PubMed Central  PubMed  Google Scholar 

  26. van Marken Lichtenbelt WD, et al. Cold-activated brown adipose tissue in healthy men. N Engl J Med. 2009;360(15):1500–8.

    PubMed  Google Scholar 

  27. Virtanen KA, et al. Functional brown adipose tissue in healthy adults. N Engl J Med. 2009;360(15):1518–25.

    CAS  PubMed  Google Scholar 

  28. Enerback S, et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature. 1997;387(6628):90–4.

    CAS  PubMed  Google Scholar 

  29. Feldmann HM, Golozoubova V, Cannon B, Nedergaard J. UCP1 ablation induces obesity and abolishes diet-induced thermogenesis in mice exempt from thermal stress by living at thermoneutrality. Cell Metab. 2009;9(2):203–9.

    CAS  PubMed  Google Scholar 

  30. Rothwell NJ, Stock MJ. Luxuskonsumption, diet-induced thermogenesis and brown fat: the case in favour. Clin Sci (Lond). 1983;64(1):19–23.

    CAS  Google Scholar 

  31. Cannon B, Nedergaard J. Thermogenesis challenges the adipostat hypothesis for bodyweight control. Proc Nutr Soc. 2009;68(4):401–7.

    PubMed  Google Scholar 

  32. Saito M, et al. High incidence of metabolically active brown adipose tissue in healthy adult humans: effects of cold exposure and adiposity. Diabetes. 2009;58(7):1526–31.

    CAS  PubMed Central  PubMed  Google Scholar 

  33. Nedergaard J, Bengtsson T, Cannon B. Unexpected evidence for active brown adipose tissue in adult humans. Am J Physiol Endocrinol Metab. 2007;293(2):E444–52.

    CAS  PubMed  Google Scholar 

  34. Zingaretti MC, et al. The presence of UCP1 demonstrates that metabolically active adipose tissue in the neck of adult humans truly represents brown adipose tissue. Faseb J. 2009;23(9):3113–20.

    CAS  PubMed  Google Scholar 

  35. Yoneshiro T, et al. Brown adipose tissue, whole-body energy expenditure, and thermogenesis in healthy adult men. Obesity (Silver Spring). 2011;19(1):13–6.

    Google Scholar 

  36. Vijgen GH, et al. Brown adipose tissue in morbidly obese subjects. PLoS ONE. 2011;6(2):e17247.

    CAS  PubMed Central  PubMed  Google Scholar 

  37. Spalding KL, et al. Dynamics of fat cell turnover in humans. Nature. 2008;453(7196):783–7.

    CAS  PubMed  Google Scholar 

  38. Tiraby C, et al. Acquirement of brown fat cell features by human white adipocytes. J Biol Chem. 2003;278(35):33370–6.

    CAS  PubMed  Google Scholar 

  39. Mazzucotelli A, et al. The transcriptional coactivator peroxisome proliferator activated receptor (PPAR)gamma coactivator-1 alpha and the nuclear receptor PPAR alpha control the expression of glycerol kinase and metabolism genes independently of PPAR gamma activation in human white adipocytes. Diabetes. 2007;56(10):2467–75.

    CAS  PubMed  Google Scholar 

  40. Enerback S. Brown adipose tissue in humans. Int J Obes. 2010;34 Suppl 1:S43–6.

    CAS  Google Scholar 

  41. Kajimura S, Seale P, Spiegelman BM. Transcriptional control of brown fat development. Cell Metab. 2010;11(4):257–62.

    CAS  PubMed Central  PubMed  Google Scholar 

  42. Nedergaard J, Cannon B. The changed metabolic world with human brown adipose tissue: therapeutic visions. Cell Metab. 2010;11(4):268–72.

    CAS  PubMed  Google Scholar 

  43. Cao L, et al. White to brown fat phenotypic switch induced by genetic and environmental activation of a hypothalamic-adipocyte axis. Cell Metab. 2011;14(3):324–38.

    CAS  PubMed Central  PubMed  Google Scholar 

  44. Guerra C, Koza RA, Yamashita H, Walsh K, Kozak LP. Emergence of brown adipocytes in white fat in mice is under genetic control. Effects on body weight and adiposity. J Clin Invest. 1998;102(2):412–20.

    CAS  PubMed Central  PubMed  Google Scholar 

  45. Xue B, et al. Genetic variability affects the development of brown adipocytes in white fat but not in interscapular brown fat. J Lipid Res. 2007;48(1):41–51.

    CAS  PubMed  Google Scholar 

  46. Vegiopoulos A, et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science. 2010;328(5982):1158–61.

    CAS  PubMed  Google Scholar 

  47. Arner P. Adrenergic receptor function in fat cells. Am J Clin Nutr. 1992;55(1 Suppl):228S–36S.

    CAS  PubMed  Google Scholar 

  48. Papetti M, Herman IM. Mechanisms of normal and tumor-derived angiogenesis. Am J Physiol Cell Physiol. 2002;282(5):C947–70.

    CAS  PubMed  Google Scholar 

  49. Zhang QX, et al. Vascular endothelial growth factor is the major angiogenic factor in omentum: mechanism of the omentum-mediated angiogenesis. J Surg Res. 1997;67(2):147–54.

    CAS  PubMed  Google Scholar 

  50. World Health Organization. Obesity: preventing and managing the global epidemic. 2000; ISBN: 92 4 120894 5.

    Google Scholar 

  51. World Health Organization International Agency for Research on Cancer. 2013; www.iarc.fr/en/media-centre/pr2013/pdfs/pr223_E.pdf.

  52. Reeves GK, et al. Cancer incidence and mortality in relation to body mass index in the Million Women Study: cohort study. BMJ. 2007;335(7630):1134.

    PubMed Central  PubMed  Google Scholar 

  53. Renehan AG, Tyson M, Egger M, Heller RF, Zwahlen M. Body-mass index and incidence of cancer: a systematic review and meta-analysis of prospective observational studies. Lancet. 2008;371(9612):569–78.

    PubMed  Google Scholar 

  54. Whitlock G, et al. Body-mass index and cause-specific mortality in 900 000 adults: collaborative analyses of 57 prospective studies. Lancet. 2009;373(9669):1083–96.

    PubMed  Google Scholar 

  55. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ. Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med. 2003;348(17):1625–38.

    PubMed  Google Scholar 

  56. Ahn J, et al. Adiposity, adult weight change, and postmenopausal breast cancer risk. Arch Intern Med. 2007;167(19):2091–102.

    PubMed  Google Scholar 

  57. Parker ED, Folsom AR. Intentional weight loss and incidence of obesity-related cancers: the Iowa Women’s Health Study. Int J Obes Relat Metab Disord. 2003;27(12):1447–52.

    CAS  PubMed  Google Scholar 

  58. Knowler WC, et al. 10-year follow-up of diabetes incidence and weight loss in the Diabetes Prevention Program Outcomes Study. Lancet. 2009;374(9702):1677–86.

    PubMed  Google Scholar 

  59. Sjostrom L, et al. Effects of bariatric surgery on mortality in Swedish obese subjects. N Engl J Med. 2007;357(8):741–52.

    PubMed  Google Scholar 

  60. Buchwald H, et al. Bariatric surgery: a systematic review and meta-analysis. JAMA. 2004;292(14):1724–37.

    CAS  PubMed  Google Scholar 

  61. Adams TD, et al. Long-term mortality after gastric bypass surgery. N Engl J Med. 2007;357(8):753–61.

    CAS  PubMed  Google Scholar 

  62. Renehan AG. Bariatric surgery, weight reduction, and cancer prevention. Lancet Oncol. 2009;10(7):640–1.

    PubMed  Google Scholar 

  63. Longo VD, Fontana L. Calorie restriction and cancer prevention: metabolic and molecular mechanisms. Trends Pharmacol Sci. 2010;31(2):89–98.

    CAS  PubMed Central  PubMed  Google Scholar 

  64. Ashrafian H, et al. Metabolic surgery and cancer: protective effects of bariatric procedures. Cancer. 2011;117(9):1788–99.

    PubMed  Google Scholar 

  65. Vona-Davis L, Rose DP. Adipokines as endocrine, paracrine, and autocrine factors in breast cancer risk and progression. Endocr Relat Cancer. 2007;14(2):189–206.

    CAS  PubMed  Google Scholar 

  66. Maccio A, et al. Correlation of body mass index and leptin with tumor size and stage of disease in hormone-dependent postmenopausal breast cancer: preliminary results and therapeutic implications. J Mol Med. 2010;88(7):677–86.

    CAS  PubMed  Google Scholar 

  67. Paz-Filho G, Lim EL, Wong ML, Licinio J. Associations between adipokines and obesity-related cancer. Front Biosci. 2011;16:1634–50.

    CAS  Google Scholar 

  68. Nkhata KJ, Ray A, Dogan S, Grande JP, Cleary MP. Mammary tumor development from T47-D human breast cancer cells in obese ovariectomized mice with and without estradiol supplements. Breast Cancer Res Treat. 2009;114(1):71–83.

    CAS  PubMed  Google Scholar 

  69. Chen DC, et al. Serum adiponectin and leptin levels in Taiwanese breast cancer patients. Cancer Lett. 2006;237(1):109–14.

    CAS  PubMed  Google Scholar 

  70. Gunter MJ, et al. Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst. 2009;101(1):48–60.

    CAS  PubMed Central  PubMed  Google Scholar 

  71. Trevisan M, et al. Markers of insulin resistance and colorectal cancer mortality. Cancer Epidemiol Biomarkers Prev. 2001;10(9):937–41.

    CAS  PubMed  Google Scholar 

  72. Jee SH, et al. Fasting serum glucose level and cancer risk in Korean men and women. JAMA. 2005;293(2):194–202.

    CAS  PubMed  Google Scholar 

  73. Rossi M, et al. Dietary glycemic load and hepatocellular carcinoma with or without chronic hepatitis infection. Ann Oncol. 2009;20(10):1736–40.

    CAS  PubMed  Google Scholar 

  74. Cao L, et al. Molecular therapy of obesity and diabetes by a physiological autoregulatory approach. Nat Med. 2009;15(4):447–54.

    CAS  PubMed Central  PubMed  Google Scholar 

  75. Coussens LM, Werb Z. Inflammation and cancer. Nature. 2002;420(6917):860–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  76. Olefsky JM. IKKepsilon: a bridge between obesity and inflammation. Cell. 2009;138(5):834–6.

    CAS  PubMed  Google Scholar 

  77. Gilbert CA, Slingerland JM. Cytokines, obesity, and cancer: new insights on mechanisms linking obesity to cancer risk and progression. Annu Rev Med. 2013;64:45–57.

    CAS  PubMed  Google Scholar 

  78. Liu X, et al. Hypothalamic gene transfer of BDNF inhibits breast cancer progression and metastasis in middle age obese mice. Mol Ther. 2014;22:1275–84.

    CAS  PubMed  Google Scholar 

  79. Magee JA, Piskounova E, Morrison SJ. Cancer stem cells: impact, heterogeneity, and uncertainty. Cancer Cell. 2012;21(3):283–96.

    CAS  PubMed  Google Scholar 

  80. Li X, et al. Intrinsic resistance of tumorigenic breast cancer cells to chemotherapy. J Natl Cancer Inst. 2008;100(9):672–9.

    CAS  PubMed  Google Scholar 

  81. Shafee N, et al. Cancer stem cells contribute to cisplatin resistance in Brca1/p53-mediated mouse mammary tumors. Cancer Res. 2008;68(9):3243–50.

    CAS  PubMed Central  PubMed  Google Scholar 

  82. Balic M, et al. Most early disseminated cancer cells detected in bone marrow of breast cancer patients have a putative breast cancer stem cell phenotype. Clin Cancer Res. 2006;12(19):5615–21.

    CAS  PubMed  Google Scholar 

  83. Korkaya H, Liu S, Wicha MS. Breast cancer stem cells, cytokine networks, and the tumor microenvironment. J Clin Invest. 2011;121(10):3804–09.

    CAS  PubMed Central  PubMed  Google Scholar 

  84. Zheng Q, et al. Leptin deficiency suppresses MMTV-Wnt-1 mammary tumor growth in obese mice and abrogates tumor initiating cell survival. Endocr Related Cancer. 2011;18(4):491–503.

    CAS  Google Scholar 

  85. Feldman DE, Chen C, Punj V, Tsukamoto H, Machida K. Pluripotency factor-mediated expression of the leptin receptor (OB-R) links obesity to oncogenesis through tumor-initiating stem cells. Proc Natl Acad Sci U S A. 2012;109(3):829–34.

    CAS  PubMed Central  PubMed  Google Scholar 

  86. Eliassen AH, Hankinson SE. Endogenous hormone levels and risk of breast, endometrial and ovarian cancers: prospective studies. Adv Exp Med Biol. 2008;630:148–65.

    CAS  PubMed  Google Scholar 

  87. Pugeat M, et al. Pathophysiology of sex hormone binding globulin (SHBG): relation to insulin. J Steroid Biochem Mol Biol. 1991;40(4–6):841–9.

    CAS  PubMed  Google Scholar 

  88. Flototto T, et al. Hormones and hormone antagonists: mechanisms of action in carcinogenesis of endometrial and breast cancer. Horm Metab Res. 2001;33(8):451–7.

    CAS  PubMed  Google Scholar 

  89. Ashrafian H. Cancer’s sweet tooth: the Janus effect of glucose metabolism in tumorigenesis. Lancet. 2006;367(9510):618–21.

    CAS  PubMed  Google Scholar 

  90. Zhang Y, et al. White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res. 2009;69(12):5259–66.

    CAS  PubMed  Google Scholar 

  91. Hanahan D, Weinberg RA. Hallmarks of cancer: the next generation. Cell. 2011;144(5):646–74.

    CAS  PubMed  Google Scholar 

  92. Reiche EM, Nunes SO, Morimoto HK. Stress, depression, the immune system, and cancer. Lancet Oncol. 2004;5(10):617–25.

    CAS  PubMed  Google Scholar 

  93. Armaiz-Pena GN, Lutgendorf SK, Cole SW, Sood AK. Neuroendocrine modulation of cancer progression. Brain Behav Immun. 2009;23(1):10–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  94. Chida Y, Hamer M, Wardle J, Steptoe A. Do stress-related psychosocial factors contribute to cancer incidence and survival? Nat Clin Pract Oncol. 2008;5(8):466–75.

    PubMed  Google Scholar 

  95. Thaker PH, Sood AK. Neuroendocrine influences on cancer biology. Semin Cancer Biol. 2008;18(3):164–70.

    CAS  PubMed Central  PubMed  Google Scholar 

  96. Glaser R, Kiecolt-Glaser JK. Stress-induced immune dysfunction: implications for health. Nat Rev Immunol. 2005;5(3):243–51.

    CAS  PubMed  Google Scholar 

  97. Antoni MH, et al. The influence of bio-behavioural factors on tumour biology: pathways and mechanisms. Nat Rev Cancer. 2006;6(3):240–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  98. Armaiz-Pena GN, Cole SW, Lutgendorf SK, Sood AK. Neuroendocrine influences on cancer progression. Brain Behav Immun. 2013;30 Suppl:S19–25.

    PubMed  Google Scholar 

  99. Cole SW. Nervous system regulation of the cancer genome. Brain Behav Immun. 2013;30 Suppl:S10–18.

    PubMed  Google Scholar 

  100. Steplewski Z, Vogel WH, Ehya H, Poropatich C, Smith JM. Effects of restraint stress on inoculated tumor growth and immune response in rats. Cancer Res. 1985;45(10):5128–33.

    CAS  PubMed  Google Scholar 

  101. Saul AN, et al. Chronic stress and susceptibility to skin cancer. J Natl Cancer Inst. 2005;97(23):1760–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  102. Sloan EK, et al. The sympathetic nervous system induces a metastatic switch in primary breast cancer. Cancer Res. 2010;70(18):7042–52.

    CAS  PubMed Central  PubMed  Google Scholar 

  103. Palermo-Neto J, de Oliveira Massoco C, Robespierre de Souza W. Effects of physical and psychological stressors on behavior, macrophage activity, and Ehrlich tumor growth. Brain Behav Immun. 2003;17(1):43–54.

    CAS  PubMed  Google Scholar 

  104. Hasegawa H, Saiki I. Psychosocial stress augments tumor development through beta-adrenergic activation in mice. Jpn J Cancer Res. 2002;93(7):729–35.

    CAS  PubMed  Google Scholar 

  105. Thaker PH, et al. Chronic stress promotes tumor growth and angiogenesis in a mouse model of ovarian carcinoma. Nat Med. 2006;12(8):939–44.

    CAS  PubMed  Google Scholar 

  106. Selye H. Stress without distress. Toronto: McClelland and Stewart, Ltd.; 1974.

    Google Scholar 

  107. Milsum JH. A model of the eustress system for health/illness. Behav Sci. 1985;30(4):179–86.

    CAS  PubMed  Google Scholar 

  108. Lapiz MD, et al. Influence of postweaning social isolation in the rat on brain development, conditioned behavior, and neurotransmission. Neurosci Behav Physiol. 2003;33(1):13–29.

    CAS  PubMed  Google Scholar 

  109. Fone KC, Porkess MV. Behavioural and neurochemical effects of post-weaning social isolation in rodents-relevance to developmental neuropsychiatric disorders. Neurosci Biobehav Rev. 2008;32(6):1087–102.

    CAS  PubMed  Google Scholar 

  110. Hasen NS, O’Leary KA, Auger AP, Schuler LA. Social isolation reduces mammary development, tumor incidence, and expression of epigenetic regulators in wild-type and p53-heterozygotic mice. Cancer Prev Res (Phila). 2010;3(5):620–9.

    CAS  Google Scholar 

  111. Williams JB, et al. A model of gene-environment interaction reveals altered mammary gland gene expression and increased tumor growth following social isolation. Cancer Prev Res (Phila). 2009;2(10):850–61.

    CAS  Google Scholar 

  112. Palermo-Neto J, Fonseca ES, Quinteiro-Filho WM, Correia CS, Sakai M. Effects of individual housing on behavior and resistance to Ehrlich tumor growth in mice. Physiol Behav. 2008;95(3):435–40.

    CAS  PubMed  Google Scholar 

  113. Algazi M, Plu-Bureau G, Flahault A, Dondon MG, Le MG. [Could treatments with betablockers be associated with a reduction in cancer risk?]. Rev Epidemiol Sante Publique. 2004;52(1):53–65.

    CAS  PubMed  Google Scholar 

  114. Perron L, Bairati I, Harel F, Meyer F. Antihypertensive drug use and the risk of prostate cancer (Canada). Cancer Causes Control. 2004;15(6):535–41.

    PubMed  Google Scholar 

  115. Melamed R, et al. Marginating pulmonary-NK activity and resistance to experimental tumor metastasis: suppression by surgery and the prophylactic use of a beta-adrenergic antagonist and a prostaglandin synthesis inhibitor. Brain Behav Immun. 2005;19(2):114–26.

    CAS  PubMed  Google Scholar 

  116. De Giorgi V, et al. Treatment with beta-blockers and reduced disease progression in patients with thick melanoma. Arch Intern Med. 2011;171(8):779–81.

    PubMed  Google Scholar 

  117. Lemeshow S, et al. β-Blockers and survival among Danish patients with malignant melanoma: a population-based cohort study. Cancer Epidemiol Biomarkers Prev. 2011;20(10):2273–9.

    CAS  PubMed Central  PubMed  Google Scholar 

  118. McEwen BS, Gianaros PJ. Central role of the brain in stress and adaptation: links to socioeconomic status, health, and disease. Ann N Y Acad Sci. 2010;1186:190–222.

    PubMed Central  PubMed  Google Scholar 

  119. Fontana L, Partridge L, Longo VD. Extending healthy life span—from yeast to humans. Science. 2010;328(5976):321–6.

    CAS  PubMed Central  PubMed  Google Scholar 

  120. Smith DL, Jr, Nagy TR, Allison DB. Calorie restriction: what recent results suggest for the future of ageing research. Eur J Clin Invest. 2010;40(5):440–50.

    CAS  PubMed Central  PubMed  Google Scholar 

  121. Mattson MP. Energy intake, meal frequency, and health: a neurobiological perspective. Annu Rev Nutr. 2005;25:237–60.

    CAS  PubMed  Google Scholar 

  122. Anderson RM, Shanmuganayagam D, Weindruch R. Caloric restriction and aging: studies in mice and monkeys. Toxicol Pathol. 2009;37(1):47–51.

    PubMed Central  PubMed  Google Scholar 

  123. Colman RJ, et al. Caloric restriction delays disease onset and mortality in rhesus monkeys. Science. 2009;325(5937):201–4.

    CAS  PubMed Central  PubMed  Google Scholar 

  124. Fontana L, Klein S. Aging, adiposity, and calorie restriction. JAMA. 2007;297(9):986–94.

    CAS  PubMed  Google Scholar 

  125. Fontana L, Meyer TE, Klein S, Holloszy JO. Long-term calorie restriction is highly effective in reducing the risk for atherosclerosis in humans. Proc Natl Acad Sci U S A. 2004;101(17):6659–63.

    CAS  PubMed Central  PubMed  Google Scholar 

  126. Heilbronn LK, et al. Effect of 6-month calorie restriction on biomarkers of longevity, metabolic adaptation, and oxidative stress in overweight individuals: a randomized controlled trial. JAMA. 2006;295(13):1539–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  127. Katic M, et al. Mitochondrial gene expression and increased oxidative metabolism: role in increased lifespan of fat-specific insulin receptor knock-out mice. Aging Cell. 2007;6(6):827–39.

    CAS  PubMed  Google Scholar 

  128. Bluher M, et al. Adipose tissue selective insulin receptor knockout protects against obesity and obesity-related glucose intolerance. Dev Cell. 2002;3(1):25–38.

    CAS  PubMed  Google Scholar 

  129. Ortega-Molina A, et al. Pten positively regulates brown adipose function, energy expenditure, and longevity. Cell Metab. 2012;15(3):382–94.

    CAS  PubMed  Google Scholar 

  130. Tsukiyama-Kohara K, et al. Adipose tissue reduction in mice lacking the translational inhibitor 4E-BP1. Nat Med. 2001;7(10):1128–32.

    CAS  PubMed  Google Scholar 

  131. Chiu CH, Lin WD, Huang SY, Lee YH. Effect of a C/EBP gene replacement on mitochondrial biogenesis in fat cells. Genes Dev. 2004;18(16):1970–5.

    CAS  PubMed Central  PubMed  Google Scholar 

  132. Molero JC, et al. c-Cbl-deficient mice have reduced adiposity, higher energy expenditure, and improved peripheral insulin action. J Clin Invest. 2004;114(9):1326–33.

    CAS  PubMed Central  PubMed  Google Scholar 

  133. Bluher M, Kahn BB, Kahn CR. Extended longevity in mice lacking the insulin receptor in adipose tissue. Science. 2003;299(5606):572–4.

    PubMed  Google Scholar 

  134. Heitmann BL, Garby L. Composition (lean and fat tissue) of weight changes in adult Danes. Am J Clin Nutr. 2002;75(5):840–7.

    CAS  PubMed  Google Scholar 

  135. Allison DB, et al. Weight loss increases and fat loss decreases all-cause mortality rate: results from two independent cohort studies. Int J Obes Relat Metab Disord. 1999;23(6):603–11.

    CAS  PubMed  Google Scholar 

  136. Brown-Borg HM. Hormonal control of aging in rodents: the somatotropic axis. Mol Cell Endocrinol. 2009;299(1):64–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  137. Otabe S, et al. Overexpression of human adiponectin in transgenic mice results in suppression of fat accumulation and prevention of premature death by high-calorie diet. Am J Physiol Endocrinol Metab. 2007;293(1):E210–8.

    CAS  PubMed  Google Scholar 

  138. Fujisawa T, et al. Adiponectin suppresses colorectal carcinogenesis under the high-fat diet condition. Gut. 2008;57(11):1531–8.

    CAS  PubMed Central  PubMed  Google Scholar 

  139. Calle EE, Kaaks R. Overweight, obesity and cancer: epidemiological evidence and proposed mechanisms. Nat Rev Cancer. 2004;4(8):579–91.

    CAS  PubMed  Google Scholar 

  140. Hursting SD, Slaga TJ, Fischer SM, DiGiovanni J, Phang JM. Mechanism-based cancer prevention approaches: targets, examples, and the use of transgenic mice. J Natl Cancer Inst. 1999;91(3):215–25.

    CAS  PubMed  Google Scholar 

  141. Albanes D. Total calories, body weight, and tumor incidence in mice. Cancer Res. 1987;47(8):1987–92.

    CAS  PubMed  Google Scholar 

  142. Wayne SJ, Rhyne RL, Garry PJ, Goodwin JS. Cell-mediated immunity as a predictor of morbidity and mortality in subjects over 60. J Gerontol. 1990;45(2):M45–8.

    CAS  PubMed  Google Scholar 

  143. DelaRosa O, et al. Immunological biomarkers of ageing in man: changes in both innate and adaptive immunity are associated with health and longevity. Biogerontology. 2006;7(5–6):471–81.

    CAS  PubMed  Google Scholar 

  144. De la Fuente M, Miquel J. An update of the oxidation-inflammation theory of aging: the involvement of the immune system in oxi-inflamm-aging. Curr Pharm Des. 2009;15(26):3003–26.

    CAS  PubMed  Google Scholar 

  145. Guayerbas N, De La Fuente M. An impairment of phagocytic function is linked to a shorter life span in two strains of prematurely aging mice. Dev Comp Immunol. 2003;27(4):339–50.

    CAS  PubMed  Google Scholar 

  146. Benaroya-Milshtein N, et al. Environmental enrichment in mice decreases anxiety, attenuates stress responses and enhances natural killer cell activity. Eur J Neurosci. 2004;20(5):1341–7.

    CAS  PubMed  Google Scholar 

  147. Larsson F, Winblad B, Mohammed AH. Psychological stress and environmental adaptation in enriched vs. impoverished housed rats. Pharmacol Biochem Behav. 2002;73(1):193–207.

    CAS  PubMed  Google Scholar 

  148. Patel NV, Finch CE. The glucocorticoid paradox of caloric restriction in slowing brain aging. Neurobiol Aging. 2002;23(5):707–17.

    CAS  PubMed  Google Scholar 

  149. Gotthardt U, et al. Cortisol, ACTH, and cardiovascular response to a cognitive challenge paradigm in aging and depression. Am J Physiol. 1995;268(4 Pt 2):R865–73.

    CAS  PubMed  Google Scholar 

  150. Witt KA, Snook JT, O’Dorisio TM, Zivony D, Malarkey WB. Exercise training and dietary carbohydrate: effects on selected hormones and the thermic effect of feeding. Int J Sport Nutr. 1993;3(3):272–89.

    CAS  PubMed  Google Scholar 

  151. Goldberg NR, Haack AK, Meshul CK. Enriched environment promotes similar neuronal and behavioral recovery in a young and aged mouse model of Parkinson’s disease. Neuroscience. 2011;172:443–52.

    CAS  PubMed  Google Scholar 

  152. Harburger LL, Lambert TJ, Frick KM. Age-dependent effects of environmental enrichment on spatial reference memory in male mice. Behav Brain Res. 2007;185(1):43–8.

    PubMed Central  PubMed  Google Scholar 

  153. Segovia G, del Arco A, Mora F. Environmental enrichment, prefrontal cortex, stress, and aging of the brain. J Neural Transm. 2009;116(8):1007–16.

    CAS  PubMed  Google Scholar 

  154. Mattson MP, Duan W, Lee J, Guo Z. Suppression of brain aging and neurodegenerative disorders by dietary restriction and environmental enrichment: molecular mechanisms. Mech Ageing Dev. 2001;122(7):757–78.

    CAS  PubMed  Google Scholar 

  155. Hannan AJ. Environmental enrichment and brain repair: harnessing the therapeutic effects of cognitive stimulation and physical activity to enhance experience-dependent plasticity. Neuropathol Appl Neurobiol. 2014;40(1):13–25.

    CAS  PubMed  Google Scholar 

  156. Woo CC, Leon M. Environmental enrichment as an effective treatment for autism: a randomized controlled trial. Behav Neurosci. 2013;127(4):487–97.

    PubMed  Google Scholar 

  157. Herrera BM, Lindgren CM. The genetics of obesity. Curr Diab Rep. 2010;10(6):498–505.

    CAS  PubMed Central  PubMed  Google Scholar 

  158. Speliotes EK, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  159. Farooqi IS, et al. Clinical spectrum of obesity and mutations in the melanocortin 4 receptor gene. N Engl J Med. 2003;348(12):1085–95.

    CAS  PubMed  Google Scholar 

  160. Calton MA, et al. Association of functionally significant Melanocortin-4 but not Melanocortin-3 receptor mutations with severe adult obesity in a large North American case-control study. Hum Mol Genet. 2009;18(6):1140–7.

    CAS  PubMed Central  PubMed  Google Scholar 

  161. Lubrano-Berthelier C, et al. Melanocortin 4 receptor mutations in a large cohort of severely obese adults: prevalence, functional classification, genotype-phenotype relationship, and lack of association with binge eating. J Clin Endocrinol Metab. 2006;91(5):1811–8.

    CAS  PubMed  Google Scholar 

  162. Farooqi S, O’Rahilly S. Genetics of obesity in humans. Endocr Rev. 2006;27(7):710–8.

    CAS  PubMed  Google Scholar 

  163. Reinehr T, et al. Lifestyle intervention in obese children with variations in the melanocortin 4 receptor gene. Obesity (Silver Spring). 2009;17(2):382–9.

    CAS  Google Scholar 

  164. Potoczna N, et al. Gene variants and binge eating as predictors of comorbidity and outcome of treatment in severe obesity. J Gastrointest Surg. 2004;8(8):971–81 (discussion 981–972).

    PubMed  Google Scholar 

  165. Flier JS. Obesity wars: molecular progress confronts an expanding epidemic. Cell. 2004;116(2):337–50.

    CAS  PubMed  Google Scholar 

  166. Xu B, et al. Brain-derived neurotrophic factor regulates energy balance downstream of melanocortin-4 receptor. Nat Neurosci. 2003;6(7):736–42.

    CAS  PubMed Central  PubMed  Google Scholar 

  167. Nicholson JR, Peter JC, Lecourt AC, Barde YA, Hofbauer KG. Melanocortin-4 receptor activation stimulates hypothalamic brain-derived neurotrophic factor release to regulate food intake, body temperature and cardiovascular function. J Neuroendocrinol. 2007;19(12):974–82.

    CAS  PubMed  Google Scholar 

  168. Speliotes EK, et al. Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index. Nat Genet. 2010;42(11):937–48.

    CAS  PubMed Central  PubMed  Google Scholar 

  169. Jiao H, et al. Genome wide association study identifies KCNMA1 contributing to human obesity. BMC Med Genomics. 2011;4:51.

    CAS  PubMed Central  PubMed  Google Scholar 

  170. Gray J, et al. Hyperphagia, severe obesity, impaired cognitive function, and hyperactivity associated with functional loss of one copy of the brain-derived neurotrophic factor (BDNF) gene. Diabetes. 2006;55(12):3366–71.

    CAS  PubMed Central  PubMed  Google Scholar 

  171. Han JC, et al. Brain-derived neurotrophic factor and obesity in the WAGR syndrome. New Engl J Med. 2008;359(9):918–27.

    CAS  PubMed Central  PubMed  Google Scholar 

  172. Yeo GS, et al. A de novo mutation affecting human TrkB associated with severe obesity and developmental delay. Nat Neurosci. 2004;7(11):1187–9.

    CAS  PubMed  Google Scholar 

  173. Han JC, Muehlbauer MJ, Cui HN, Newgard CB, Haqq AM. Lower brain-derived neurotrophic factor in patients with prader-willi syndrome compared to obese and lean control subjects. J Clin Endocrinol Metab. 2010;95(7):3532–6.

    CAS  PubMed Central  PubMed  Google Scholar 

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Acknowledgments

I am grateful to the past and present lab members for their data and discussions that have helped me to form my ideas of this chapter. I am currently funded by grants from the National Institutes of Health (NCI R01-CA166590, NCI R01-CA163640, NCI R21-CA178227, and NIA R01-AG041250).

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  1. College of Medicine, The Ohio State University, 910 BRT, 460 W 12th Avenue, 43210, Columbus, OH, USA

    Lei Cao PhD

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  1. Center for Science, Health & Society, Case Western Reserve University School of Medicine, Cleveland, Ohio, USA

    Nathan A. Berger

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Cao, L. (2015). Environmental Manipulation and Neuropeptide Effects on Energy Balance and Cancer. In: Berger, N. (eds) Murine Models, Energy Balance, and Cancer. Energy Balance and Cancer, vol 10. Springer, Cham. https://doi.org/10.1007/978-3-319-16733-6_2

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