Top

Published in:

01-06-2018 | Original Contribution

Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat

Authors: Roberto Coccurello, Adele Romano, Giacomo Giacovazzo, Bianca Tempesta, Marco Fiore, Anna Maria Giudetti, Ilaria Marrocco, Fabio Altieri, Anna Moles, Silvana Gaetani

Published in: European Journal of Nutrition | Issue 4/2018

Abstract

Purpose

Chronic exposure to stress may represent a risk factor for developing metabolic and eating disorders, mostly driven by the overconsumption of easily accessible energy-dense palatable food, although the mechanisms involved remain still unclear. In this study, we used an ethologically oriented murine model of chronic stress caused by chronic psychosocial defeat (CPD) to investigate the effects of unrestricted access to a palatable high fat diet (HFD) on food intake, body weight, energy homeostasis, and expression of different brain neuropeptides. Our aim was to shed light on the mechanisms responsible for body weight and body composition changes due to chronic social stress.

Methods

In our model of subordinate (defeated), mice (CPD) cohabitated in constant sensory contact with dominants, being forced to interact on daily basis, and were offered ad libitum access either to an HFD or to a control diet (CD). Control mice (of the same strain as CPD mice) were housed in pairs and left unstressed in their home cage (UN). In all these mice, we evaluated body weight, different adipose depots, energy metabolism, caloric intake, and neuropeptide expression.

Results

CPD mice increased the intake of HFD and reduced body weight in the presence of enhanced lipid oxidation. Resting energy expenditure and interscapular brown adipose tissue (iBAT) were increased in CPD mice, whereas epididymal adipose tissue increased only in HFD-fed unstressed mice. Propiomelanocortin mRNA levels in hypothalamic arcuate nucleus increased only in HFD-fed unstressed mice. Oxytocin mRNA levels in the paraventricular nucleus and neuropeptide Y mRNA levels within the arcuate were increased only in CD-fed CPD mice. In the arcuate, CART was increased in HFD-fed UN mice and in CD-fed CPD mice, while HFD intake suppressed CART increase in defeated animals. In the basolateral amygdala, CART expression was increased only in CPD animals on HFD.

Conclusions

CPD appears to uncouple the intake of HFD from energy homeostasis causing higher HFD intake, larger iBAT accumulation, increased energy expenditure and lipid oxidation, and lower body weight. Overall, the present study confirms the notion that the chronic activation of the stress response can be associated with metabolic disorders, altered energy homeostasis, and changes of orexigenic and anorexigenic signaling. These changes might be relevant to better understand the etiology of stress-induced obesity and eating disorders and might represent a valid therapeutic approach for the development of new therapies in this field.

Coccurello R, D’Amato FR, Moles A (2009) Chronic social stress, hedonism and vulnerability to obesity: lessons from Rodents. Neurosci Biobehav Rev 33:537–550. doi:10.1016/j.neubiorev.2008.05.018 CrossRefPubMed

Berthoud H-R (2006) Homeostatic and non-homeostatic pathways involved in the control of food intake and energy balance. Obesity 14:197S–200S. doi:10.1038/oby.2006.308 CrossRefPubMed

Lutter M, Nestler EJ (2009) Homeostatic and hedonic signals interact in the regulation of food intake. J Nutr 139:629–632. doi:10.3945/jn.108.097618 CrossRefPubMedPubMedCentral

Volkow ND, Wise RA (2005) How can drug addiction help us understand obesity? Nat Neurosci 8:555–560. doi:10.1038/nn1452 CrossRefPubMed

Saper CB, Chou TC, Elmquist JK (2002) The need to feed: homeostatic and hedonic control of eating. Neuron 36:199–211. doi:10.1016/S0896-6273(02)00969-8 CrossRefPubMed

Björntorp P (2001) Do stress reactions cause abdominal obesity and comorbidities? Obes Rev 2:73–86. doi:10.1046/j.1467-789x.2001.00027.x CrossRefPubMed

Adam TC, Epel ES (2007) Stress, eating and the reward system. Physiol Behav 91:449–458. doi:10.1016/j.physbeh.2007.04.011 CrossRefPubMed

Moles A, Bartolomucci A, Garbugino L et al (2006) Psychosocial stress affects energy balance in mice: modulation by social status. Psychoneuroendocrinology 31:623–633. doi:10.1016/j.psyneuen.2006.01.004 CrossRefPubMed

Kivimaki M, Head J, Ferrie JE et al (2006) Work stress, weight gain and weight loss: evidence for bidirectional effects of job strain on body mass index in the Whitehall II study. Int J Obes 30:982–987. doi:10.1038/sj.ijo.0803229 CrossRef

10.

Dallman MF (2010) Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab 21:159–165. doi:10.1016/j.tem.2009.10.004 CrossRefPubMed

11.

Martí O, Martí J, Armario A (1994) Effects of chronic stress on food intake in rats: influence of stressor intensity and duration of daily exposure. Physiol Behav 55:747–753CrossRefPubMed

12.

Blanchard DC, Spencer RL, Weiss SM et al (1995) Visible burrow system as a model of chronic social stress: behavioral and neuroendocrine correlates. Psychoneuroendocrinology 20:117–134. doi:10.1016/0306-4530(94)E0045-B CrossRefPubMed

13.

Harris RB, Zhou J, Youngblood BD et al (1998) Effect of repeated stress on body weight and body composition of rats fed low- and high-fat diets. Am J Physiol 275:R1928–R1938PubMed

14.

Haller J, Fuchs E, Halász J, Makara GB (1999) Defeat is a major stressor in males while social instability is stressful mainly in females: towards the development of a social stress model in female rats. Brain Res Bull 50:33–39. doi:10.1016/S0361-9230(99)00087-8 CrossRefPubMed

15.

Vallès A, Martí O, García A, Armario A (2000) Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats. Am J Physiol Regul Integr Comp Physiol 279:R1138–R1144CrossRefPubMed

16.

Fuchs E, Flügge G (2002) Social stress in tree shrews: effects on physiology, brain function, and behavior of subordinate individuals. Pharmacol Biochem Behav 73:247–258. doi:10.1016/S0091-3057(02)00795-5 CrossRefPubMed

17.

Tamashiro KLK, Nguyen MMN, Sakai RR (2005) Social stress: from rodents to primates. Front Neuroendocrinol 26:27–40. doi:10.1016/j.yfrne.2005.03.001 CrossRefPubMed

18.

Bartolomucci A, Pederzani T, Sacerdote P et al (2004) Behavioral and physiological characterization of male mice under chronic psychosocial stress. Psychoneuroendocrinology 29:899–910. doi:10.1016/j.psyneuen.2003.08.003 CrossRefPubMed

19.

Foster MT, Solomon MB, Huhman KL, Bartness TJ (2006) Social defeat increases food intake, body mass, and adiposity in Syrian hamsters. Am J Physiol Regul Integr Comp Physiol 290:R1284–R1293. doi:10.1152/ajpregu.00437.2005 CrossRefPubMed

20.

Solomon MB, Foster MT, Bartness TJ, Huhman KL (2007) Social defeat and footshock increase body mass and adiposity in male Syrian hamsters. Am J Physiol Regul Integr Comp Physiol 292:R283–R290. doi:10.1152/ajpregu.00330.2006 CrossRefPubMed

21.

Bartolomucci A, Cabassi A, Govoni P et al (2009) Metabolic consequences and vulnerability to diet-induced obesity in male mice under chronic social stress. PLoS One. doi:10.1371/journal.pone.0004331 CrossRefPubMedPubMedCentral

22.

Finger BC, Dinan TG, Cryan JF (2012) The temporal impact of chronic intermittent psychosocial stress on high-fat diet-induced alterations in body weight. Psychoneuroendocrinology 37:729–741. doi:10.1016/j.psyneuen.2011.06.015 CrossRefPubMed

23.

Nonogaki K, Nozue K, Oka Y (2007) Social isolation affects the development of obesity and type 2 diabetes in mice. Endocrinology 148:4658–4666. doi:10.1210/en.2007-0296 CrossRefPubMed

24.

Balsevich G, Uribe A, Wagner KV et al (2014) Interplay between diet-induced obesity and chronic stress in mice: potential role of FKBP51. J Endocrinol 222:15–26. doi:10.1530/JOE-14-0129 CrossRefPubMed

25.

Sanghez V, Razzoli M, Carobbio S et al (2013) Psychosocial stress induces hyperphagia and exacerbates diet-induced insulin resistance and the manifestations of the metabolic syndrome. Psychoneuroendocrinology 38:2933–2942. doi:10.1016/j.psyneuen.2013.07.022 CrossRefPubMed

26.

Blanchard RJ, McKittrick CR, Blanchard DC (2001) Animal models of social stress: effects on behavior and brain neurochemical systems. Physiol Behav 73:261–271. doi:10.1016/S0031-9384(01)00449-8 CrossRefPubMed

27.

Gaetani S, Fu J, Cassano T et al (2010) The fat-induced satiety factor oleoylethanolamide suppresses feeding through central release of oxytocin. J Neurosci 30:8096–8101. doi:10.1523/JNEUROSCI.0036-10.2010 CrossRefPubMedPubMedCentral

28.

Romano A, Potes CS, Tempesta B et al (2013) Hindbrain noradrenergic input to the hypothalamic PVN mediates the activation of oxytocinergic neurons induced by the satiety factor oleoylethanolamide. Am J Physiol Endocrinol Metab 305:E1266–E1273. doi:10.1152/ajpendo.00411.2013 CrossRefPubMed

29.

Romano a., Karimian Azari E, Tempesta B et al (2014) High dietary fat intake influences the activation of specific hindbrain and hypothalamic nuclei by the satiety factor oleoylethanolamide. Physiol Behav 136:55–62. doi:10.1016/j.physbeh.2014.04.039 CrossRefPubMed

30.

Miller JA (1991) The calibration of 35S or 32P with 14C-labeled brain paste or 14C-plastic standards for quantitative autoradiography using LKB Ultrofilm or Amersham Hyperfilm. Neurosci Lett 121:211–214

31.

Paxinos G, Franklin KBJ (2004) The mouse brain in stereotaxic coordinates. Academic Press, London. doi:10.1016/S0306-4530(03)00088-X CrossRef

32.

Strissel KJ, Stancheva Z, Miyoshi H et al (2007) Adipocyte death, adipose tissue remodeling, and obesity complications. Diabetes 56:2910–2918. doi:10.2337/db07-0767 CrossRefPubMed

33.

Preitner F, Mody N, Graham TE et al (2009) Long-term Fenretinide treatment prevents high-fat diet-induced obesity, insulin resistance, and hepatic steatosis. Am J Physiol Endocrinol Metab 297:E1420–E1429. doi:10.1152/ajpendo.00362.2009 CrossRefPubMedPubMedCentral

34.

Mulder P, Morrison MC, Wielinga PY, et al (2015) Surgical removal of inflamed epididymal white adipose tissue attenuates the development of non-alcoholic steatohepatitis in obesity. Int J Obes (Lond):1–10. doi:10.1038/ijo.2015.226

35.

Razzoli M, Frontini A, Gurney A, et al (2016) Stress-induced activation of brown adipose tissue prevents obesity in conditions of low adaptive thermogenesis. Mol Metab 5:19–33. doi:10.1016/j.molmet.2015.10.005 CrossRefPubMed

36.

Tamashiro KLK, Nguyen MMN, Fujikawa T et al (2004) Metabolic and endocrine consequences of social stress in a visible burrow system. Physiol Behav 80:683–693. doi:10.1016/j.physbeh.2003.12.002 CrossRefPubMed

37.

Choi DC, Nguyen MMN, Tamashiro KLK et al (2006) Chronic social stress in the visible burrow system modulates stress-related gene expression in the bed nucleus of the stria terminalis. Physiol Behav 89:301–310. doi:10.1016/j.physbeh.2006.05.046 CrossRefPubMed

38.

Nguyen MMN, Tamashiro KLK, Melhorn SJ et al (2007) Androgenic influences on behavior, body weight, and body composition in a model of chronic social stress. Endocrinology 148:6145–6156. doi:10.1210/en.2007-0471 CrossRefPubMed

39.

Lkhagvasuren B, Nakamura Y, Oka T et al (2011) Social defeat stress induces hyperthermia through activation of thermoregulatory sympathetic premotor neurons in the medullary raphe region. Eur J Neurosci 34:1442–1452. doi:10.1111/j.1460-9568.2011.07863.x CrossRefPubMed

40.

Kataoka N, Hioki H, Kaneko T, Nakamura K (2014) Psychological stress activates a dorsomedial hypothalamus-medullary raphe circuit driving brown adipose tissue thermogenesis and hyperthermia. Cell Metab 20:346–358. doi:10.1016/j.cmet.2014.05.018 CrossRefPubMed

41.

Tamashiro KLK, Hegeman M a., Sakai RR (2006) Chronic social stress in a changing dietary environment. Physiol Behav 89:536–542. doi:10.1016/j.physbeh.2006.05.026 CrossRefPubMed

42.

Nishioka T, Anselmo-Franci JA, Li P et al (1998) Stress increases oxytocin release within the hypothalamic paraventricular nucleus. Brain Res 781:57–61. doi:10.1016/S0006-8993(97)01159-1 CrossRefPubMed

43.

Wotjak CT, Ganster J, Kohl G et al (1998) Dissociated central and peripheral release of vasopressin, but not oxytocin, in response to repeated swim stress: new insights into the secretory capacities of peptidergic neurons. Neuroscience 85:1209–1222. doi:10.1016/S0306-4522(97)00683-0 CrossRefPubMed

44.

Wigger A, Neumann ID (2002) Endogenous opioid regulation of stress-induced oxytocin release within the hypothalamic paraventricular nucleus is reversed in late pregnancy: a microdialysis study. Neuroscience 112:121–129. doi:10.1016/S0306-4522(02)00068-4 CrossRefPubMed

45.

Raffin-Sanson ML, de Keyzer Y, Bertagna X (2003) Proopiomelanocortin, a polypeptide precursor with multiple functions: from physiology to pathological conditions. Eur J Endocrinol 149:79–90. doi:10.1530/eje.0.1490079 CrossRefPubMed

46.

Pritchard LE, Turnbull AV, White A (2002) Pro-opiomelanocortin processing in the hypothalamus: impact on melanocortin signalling and obesity. J Endocrinol 172:411–421. doi:10.1677/joe.0.1720411 CrossRefPubMed

47.

Mountjoy KG (2015) Pro-opiomelanocortin (POMC) neurones, POMC-derived peptides, melanocortin receptors and obesity: how understanding of this system has changed over the last decade. J Neuroendocrinol 27:406–418. doi:10.1111/jne.12285 CrossRefPubMed

48.

Liu S, Globa AK, Mills F et al (2016) Consumption of palatable food primes food approach behavior by rapidly increasing synaptic density in the VTA. Proc Natl Acad Sci USA 113:2520–2525. doi:10.1073/pnas.1515724113 CrossRefPubMed

49.

Romano A, Cassano T, Tempesta B et al (2013) The satiety signal oleoylethanolamide stimulates oxytocin neurosecretion from rat hypothalamic neurons. Peptides 49:21–26. doi:10.1016/j.peptides.2013.08.006 CrossRefPubMed

50.

Provensi G, Coccurello R, Umehara H et al (2014) Satiety factor oleoylethanolamide recruits the brain histaminergic system to inhibit food intake. Proc Natl Acad Sci USA 111:11527–11532. doi:10.1073/pnas.1322016111 CrossRefPubMed

51.

Romano A, Tempesta B, Di Bonaventura MVM, Gaetani S (2016) From autism to eating disorders and more: the role of oxytocin in neuropsychiatric disorders. Front Neurosci. doi:10.3389/fnins.2015.00497 CrossRefPubMedPubMedCentral

52.

Callahan MF, Thore CR, Sundberg DK et al (1992) Excitotoxin paraventricular nucleus lesions: stress and endocrine reactivity and oxytocin mRNA levels. Brain Res 597:8–15. doi:10.1016/0006-8993(92)91499-5 CrossRefPubMed

53.

Hashiguchi H, Ye SH, Morris M, Alexander N (1997) Single and repeated environmental stress: effect on plasma oxytocin, corticosterone, catecholamines, and behavior. Physiol Behav 61:731–736. doi:10.1016/S0031-9384(96)00527-6 CrossRefPubMed

54.

Iványi T, Wiegant VM, de Wied D (1991) Differential effects of emotional and physical stress on the central and peripheral secretion of neurohypophysial hormones in male rats. Life Sci 48:1309–1316CrossRefPubMed

55.

Kalyani M, Hasselfeld K, Janik JM et al (2016) Effects of high-fat diet on stress response in male and female wildtype and prolactin knockout mice. PLoS One. doi:10.1371/journal.pone.0166416 CrossRefPubMedPubMedCentral

56.

Morton GJ, Thatcher BS, Reidelberger RD, et al (2012) Peripheral oxytocin suppresses food intake and causes weight loss in diet-induced obese rats. AJP Endocrinol Metab 302:E134–E144. doi:10.1152/ajpendo.00296.2011 CrossRef

57.

Billings LB, Spero J a, Vollmer RR, Amico J a (2006) Oxytocin null mice ingest enhanced amounts of sweet solutions during light and dark cycles and during repeated shaker stress. Behav Brain Res 171:134–141. doi:10.1016/j.bbr.2006.03.028 CrossRefPubMed

58.

Chambers AP, Woods SC (2012) The role of neuropeptide Y in energy homeostasis. Handb Exp Pharmacol:23–45. doi:10.1007/978-3-642-24716-3_2

59.

Heilig M (2004) The NPY system in stress, anxiety and depression. Neuropeptides 38:213–224. doi:10.1016/j.npep.2004.05.002 CrossRefPubMed

60.

Beck B (2006) Neuropeptide Y in normal eating and in genetic and dietary-induced obesity. Philos Trans R Soc Lond B Biol Sci 361:1159–1185. doi:10.1098/rstb.2006.1855 CrossRefPubMedPubMedCentral

61.

Reichmann F, Holzer P (2016) Neuropeptide Y: a stressful review. Neuropeptides 55:99–109. doi:10.1016/j.npep.2015.09.008 CrossRefPubMed

62.

Ulrich-lai YM, Fulton S, Wilson M et al (2015) Stress exposure, food intake and emotional state. Stress 0:1–19. doi:10.3109/10253890.2015.1062981 CrossRef

63.

Vicentic A, Jones DC (2007) The CART (cocaine- and amphetamine-regulated transcript) system in appetite and drug addiction. J Pharmacol Exp Ther 320:499–506. doi:10.1124/jpet.105.091512 CrossRefPubMed

64.

Rogge G, Jones D, Hubert GW et al (2008) CART peptides: regulators of body weight, reward and other functions. Nat Rev Neurosci 9:747–758. doi:10.1038/nrn2806 CrossRefPubMedPubMedCentral

65.

Bharne AP, Borkar CD, Subhedar NK, Kokare DM (2015) Differential expression of CART in feeding and reward circuits in binge eating rat model. Behav Brain Res 291:219–231. doi:10.1016/j.bbr.2015.05.030 CrossRefPubMed

66.

Koylu EO, Balkan B, Kuhar MJ, Pogun S (2006) Cocaine and amphetamine regulated transcript (CART) and the stress response. Peptides 27:1956–1969. doi:10.1016/j.peptides.2006.03.032 CrossRefPubMed

67.

Rademacher DJ, Sullivan EM, Figge D a (2010) The effects of infusions of CART 55–102 into the basolateral amygdala on amphetamine-induced conditioned place preference in rats. Psychopharmacology (Berl) 208:499–509. doi:10.1007/s00213-009-1748-4 CrossRef

68.

Ulrich-Lai YM, Christiansen AM, Ostrander MM et al (2010) Pleasurable behaviors reduce stress via brain reward pathways. Proc Natl Acad Sci USA 107:20529–20534. doi:10.1073/pnas.1007740107 CrossRefPubMed

69.

Mcewen BS (1998) Protectice and damaging effects of stress mediators. N Engl J Med 338:171–179. doi:10.1056/NEJM199801153380307 CrossRefPubMed

70.

Dallman MF, Pecoraro N, Akana SF, et al (2003) Chronic stress and obesity: a new view of “comfort food”. Proc Natl Acad Sci 100:11696–11701. doi:10.1073/pnas.1934666100 CrossRefPubMed

71.

Dallman MF, La Fleur SE, Pecoraro NC et al (2004) Minireview: glucocorticoids—food intake, abdominal obesity, and wealthy nations in 2004. Endocrinology 145:2633–2638. doi:10.1210/en.2004-0037 CrossRefPubMed

72.

Sapolsky RM, Romero LM, Munck a. U (2000) How do glucocorticoids influence stress responses^†¯? Preparative actions*. Endocr Rev 21:55–89. doi:10.1210/er.21.1.55 CrossRefPubMed

73.

Dallman MF, Strack AM, Akana SF et al (1993) Feast and famine: critical role of glucocorticoids with insulin in daily energy flow. Front Neuroendocrinol 14:303–347. doi:10.1006/frne.1993.1010 CrossRefPubMed

Title: Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat
Authors: Roberto Coccurello
Adele Romano
Giacomo Giacovazzo
Bianca Tempesta
Marco Fiore
Anna Maria Giudetti
Ilaria Marrocco
Fabio Altieri
Anna Moles
Silvana Gaetani
Publication date: 01-06-2018
Publisher: Springer Berlin Heidelberg
Published in: European Journal of Nutrition / Issue 4/2018
Print ISSN: 1436-6207
Electronic ISSN: 1436-6215
DOI: https://doi.org/10.1007/s00394-017-1434-y

ACC 2024 Congress Coverage

Heart Failure Video

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Increased intake of energy-dense diet and negative energy balance in a mouse model of chronic psychosocial defeat

Abstract

Purpose

Methods

Results

Conclusions

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page

At a glance: The ONWARDS insulin icodec trials

Springer Medicine

Abstract

Purpose

Methods

Results

Conclusions

Please log in to get access to this content

Other articles of this Issue 4/2018

Association of the Baltic Sea and Mediterranean diets with indices of sarcopenia in elderly women, OSPTRE-FPS study

Adherence to a Mediterranean-style diet and incident fractures: pooled analysis of observational evidence

Methyl-donor depletion of head and neck cancer cells in vitro establishes a less aggressive tumour cell phenotype

Physiological activities of the combination of fish oil and α-lipoic acid affecting hepatic lipogenesis and parameters related to oxidative stress in rats

Prospective associations between dietary patterns and high sensitivity C-reactive protein in European children: the IDEFICS study

Alcohol and red wine consumption, but not fruit, vegetables, fish or dairy products, are associated with less endothelial dysfunction and less low-grade inflammation: the Hoorn Study

ACC 2024 Congress Coverage

Year in Review: Heart failure and cardiomyopathies

Semaglutide benefits people with type 2 diabetes and obesity-related heart failure

Incentivised to exercise

New intervention for STEMI-related cardiogenic shock

» View more highlights on the ACC 2024 congress hub page