Effects of Isolation and Social Subchronic Stresses on Food Intake and Levels of Leptin, Ghrelin, and Glucose in Male Rats

Document Type : Original Article


Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran


Background: Exposure to psychological stresses can be a reason for obesity. Therefore, identifying the effective nutritional mechanisms such as feeding markers is of high necessity for the psychological stress conditions. Hence, the present study investigates the effects of subchronic isolation and social stresses on food intake, body weight differences (BWD), and levels of leptin, ghrelin, and glucose in rats. Materials and Methods: Eighteen male rats were randomly allocated into three groups: control (Co), isolation stress (IS), and social stress (SS) groups. Rats were under stresses for 7 days. The food intake (for three continuous hours after 16–18 h of food deprivation), BWD, levels of ghrelin, leptin, and glucose were measured. Results: The results showed that the food intake significantly (P < 0.05) reduced during the 1st h in the SS group compared to the Co group. At the 2nd h, the food intake significantly (P < 0.001 and P < 0.01, respectively) decreased in the IS group compared to the Co and SS groups. The cumulative food intake and body weight were significantly (P < 0.05) reduced in the IS group compared to the Co group. The serum ghrelin level significantly reduced in the IS group compared to the Co group. Conclusions: The subchronic psychological stresses led to a reduction in food intake by the reduction of serum ghrelin levels. It seems that ghrelin might have a more fundamental role in the food intake with respect to the leptin and glucose levels in subchronic stress condition. Furthermore, the decreased body weight justified the reduction of food intake, particularly in subchronic isolation stress.


Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell 2001;104:531-43.  Back to cited text no. 1
Sobrino Crespo C, Perianes Cachero A, Puebla Jiménez L, Barrios V, Arilla Ferreiro E. Peptides and food intake. Front Endocrinol (Lausanne) 2014;5:58.  Back to cited text no. 2
Spencer SJ. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress. Front Neurosci 2013;7:109.  Back to cited text no. 3
Torres SJ, Nowson CA. Relationship between stress, eating behavior, and obesity. Nutrition 2007;23:887-94.  Back to cited text no. 4
Ergang P, Vodička M, Soták M, Klusoňová P, Behuliak M, Řeháková L, et al. Differential impact of stress on hypothalamic-pituitary-adrenal axis: Gene expression changes in Lewis and Fisher rats. Psychoneuroendocrinology 2015;53:49-59.  Back to cited text no. 5
Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav 2007;91:449-58.  Back to cited text no. 6
Huang TT, Drewnosksi A, Kumanyika S, Glass TA. A systems-oriented multilevel framework for addressing obesity in the 21st century. Prev Chronic Dis 2009;6:A82.  Back to cited text no. 7
Chen Y. Regulation of food intake and the development of anti-obesity drugs. Drug Discov Ther 2016;10:62-73.  Back to cited text no. 8
Fischer EK, O'Connell LA. Modification of feeding circuits in the evolution of social behavior. J Exp Biol 2017;220:92-102.  Back to cited text no. 9
Farr OM, Li CS, Mantzoros CS. Central nervous system regulation of eating: Insights from human brain imaging. Metabolism 2016;65:699-713.  Back to cited text no. 10
Jaggi AS, Bhatia N, Kumar N, Singh N, Anand P, Dhawan R, et al. A review on animal models for screening potential anti-stress agents. Neurol Sci 2011;32:993-1005.  Back to cited text no. 11
Ranjbar H, Radahmadi M, Alaei H, Reisi P, Karimi S. The effect of basolateral amygdala nucleus lesion on memory under acute, mid and chronic stress in male rats. Turk J Med Sci 2016;46:1915-25.  Back to cited text no. 12
Rabasa C, Dickson SL. Impact of stress on metabolism and energy balance. Curr Opin Behav Sci 2016;9:71-7.  Back to cited text no. 13
Radahmadi M, Alaei H, Sharifi MR, Hosseini N. Effects of different timing of stress on corticosterone, BDNF and memory in male rats. Physiol Behav 2015;139:459-67.  Back to cited text no. 14
Bali A, Singh N, Jaggi AS. Neuropeptides as therapeutic targets to combat stress-associated behavioral and neuroendocrinological effects. CNS Neurol Disord Drug Targets 2014;13:347-68.  Back to cited text no. 15
Ranjbar H, Radahmadi M, Alaei H, Reisi P. Effect of different durations of stress on spatial and cognitive memory in male rats. J Isfahan Med Sch 2014;32:1933-43.  Back to cited text no. 16
Ranjbar H, Radahmadi M, Reisi P, Alaei H. Effects of electrical lesion of basolateral amygdala nucleus on rat anxiety-like behaviour under acute, sub-chronic, and chronic stresses. Clin Exp Pharmacol Physiol 2017;44:470-9.  Back to cited text no. 17
Radahmadi M, Hosseini Dastgerdi A, Fallah N, Alaei H. The effects of acute, sub-chronic and chronic psychical stress on the brain electrical activity in male rats. Physiol Pharmacol 2017;21:185-92.  Back to cited text no. 18
Oliver G, Wardle J, Gibson EL. Stress and food choice: A laboratory study. Psychosom Med 2000;62:853-65.  Back to cited text no. 19
Stengel A, Taché Y. Neuroendocrine control of the gut during stress: Corticotropin-releasing factor signaling pathways in the spotlight. Annu Rev Physiol 2009;71:219-39.  Back to cited text no. 20
Ulrich-Lai YM, Fulton S, Wilson M, Petrovich G, Rinaman L. Stress exposure, food intake and emotional state. Stress 2015;18:381-99.  Back to cited text no. 21
Shively CA, Fimmel A, Jones S, Nader M. Dietary modification of physiological responses to chronic psychosocial stress: Implications for the obesity epidemic. In: Shively CA, Wilson ME, editors. Social Inequalities in Health in Nonhuman Primates: The Biology of the Gradient. Cham: Springer International Publishing; 2016. p. 159-78.  Back to cited text no. 22
la Fleur SE. The effects of glucocorticoids on feeding behavior in rats. Physiol Behav 2006;89:110-4.  Back to cited text no. 23
Grippo AJ, Gerena D, Huang J, Kumar N, Shah M, Ughreja R, et al. Social isolation induces behavioral and neuroendocrine disturbances relevant to depression in female and male prairie voles. Psychoneuroendocrinology 2007;32:966-80.  Back to cited text no. 24
Kalshetti PB, Alluri R, Mohan V, Thakurdesai PA. Effects of 4-hydroxyisoleucine from fenugreek seeds on depression-like behavior in socially isolated olfactory bulbectomized rats. Pharmacogn Mag 2015;11:S388-96.  Back to cited text no. 25
Patki G, Solanki N, Atrooz F, Allam F, Salim S. Depression, anxiety-like behavior and memory impairment are associated with increased oxidative stress and inflammation in a rat model of social stress. Brain Res 2013;1539:73-86.  Back to cited text no. 26
Kristenssson E, Sundqvist M, Astin M, Kjerling M, Mattsson H, Dornonville de la Cour C, et al. Acute psychological stress raises plasma ghrelin in the rat. Regul Pept 2006;134:114-7.  Back to cited text no. 27
Rayatpour A, Ghasemi M, Radahmadi M, Izadi M. Effect of intraparaventricular administration of corticotropin-releasing hormone on food intake in food-deprived rats. J Isfahan Med Sch 2017;35:770-5.  Back to cited text no. 28
Izadi M, Radahmadi M, Ghasemi M, Rayatpour A. Effect of repeated administration of corticotropin-releasing hormone (CRH) in central amygdala nucleus on feeding behavior in adult male rats. J Isfahan Med Sch 2017;35:707-12.  Back to cited text no. 29
Mirmohammadsadeghi Z, Shareghi Brojeni M, Haghparast A, Eliassi A. Role of paraventricular hypothalamic dopaminergic D1 receptors in food intake regulation of food-deprived rats. Eur J Pharmacol 2018;818:43-9.  Back to cited text no. 30
Salimi M, Eliassi A, Haghparast A. Intra-paraventricular nucleus microinjection of D2 receptors antagonist, sulpiride, reduces food intake in 24 hours food-deprived rats. Iran J Physiol Pharmacol 2015;1:193-86.  Back to cited text no. 31
Appelhans BM, Pagoto SL, Peters EN, Spring BJ. HPA axis response to stress predicts short-term snack intake in obese women. Appetite 2010;54:217-20.  Back to cited text no. 32
George SA, Khan S, Briggs H, Abelson JL. CRH-stimulated cortisol release and food intake in healthy, non-obese adults. Psychoneuroendocrinology 2010;35:607-12.  Back to cited text no. 33
Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab 2010;21:159-65.  Back to cited text no. 34
Ortolani D, Oyama LM, Ferrari EM, Melo LL, Spadari-Bratfisch RC. Effects of comfort food on food intake, anxiety-like behavior and the stress response in rats. Physiol Behav 2011;103:487-92.  Back to cited text no. 35
Vallès A, Martí O, García A, Armario A. Single exposure to stressors causes long-lasting, stress-dependent reduction of food intake in rats. Am J Physiol Regul Integr Comp Physiol 2000;279:R1138-44.  Back to cited text no. 36
Gamaro GD, Manoli LP, Torres IL, Silveira R, Dalmaz C. Effects of chronic variate stress on feeding behavior and on monoamine levels in different rat brain structures. Neurochem Int 2003;42:107-14.  Back to cited text no. 37
Torres IL, Gamaro GD, Vasconcellos AP, Silveira R, Dalmaz C. Effects of chronic restraint stress on feeding behavior and on monoamine levels in different brain structures in rats. Neurochem Res 2002;27:519-25.  Back to cited text no. 38
Bazhan N, Zelena D. Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis. Brain Res Bull 2013;95:46-53.  Back to cited text no. 39
Sominsky L, Spencer SJ. Eating behavior and stress: A pathway to obesity. Front Psychol 2014;5:434.  Back to cited text no. 40
Currie PJ, Khelemsky R, Rigsbee EM, Dono LM, Coiro CD, Chapman CD, et al. Ghrelin is an orexigenic peptide and elicits anxiety-like behaviors following administration into discrete regions of the hypothalamus. Behav Brain Res 2012;226:96-105.  Back to cited text no. 41
Spencer SJ, Emmerzaal TL, Kozicz T, Andrews ZB. Ghrelin's role in the hypothalamic-pituitary-adrenal axis stress response: Implications for mood disorders. Biol Psychiatry 2015;78:19-27.  Back to cited text no. 42
Saegusa Y, Takeda H, Muto S, Nakagawa K, Ohnishi S, Sadakane C, et al. Decreased plasma ghrelin contributes to anorexia following novelty stress. Am J Physiol Endocrinol Metab 2011;301:E685-96.  Back to cited text no. 43
Schellekens H, Finger BC, Dinan TG, Cryan JF. Ghrelin signalling and obesity: At the interface of stress, mood and food reward. Pharmacol Ther 2012;135:316-26.  Back to cited text no. 44
Lutter M, Sakata I, Osborne-Lawrence S, Rovinsky SA, Anderson JG, Jung S, et al. The orexigenic hormone ghrelin defends against depressive symptoms of chronic stress. Nat Neurosci 2008;11:752-3.  Back to cited text no. 45
Uchida A, Zigman JM, Perelló M. Ghrelin and eating behavior: Evidence and insights from genetically-modified mouse models. Front Neurosci 2013;7:121.  Back to cited text no. 46
Bernier NJ, Gorissen M, Flik G. Differential effects of chronic hypoxia and feed restriction on the expression of leptin and its receptor, food intake regulation and the endocrine stress response in common carp. J Exp Biol 2012;215:2273-82.  Back to cited text no. 47
Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 2008;70:537-56.  Back to cited text no. 48
Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000;62:413-37.  Back to cited text no. 49
Chojnowska K, Czerwinska J, Kaminski T, Kaminska B, Kurzynska A, Bogacka I, et al. Leptin plasma concentrations, leptin gene expression, and protein localization in the hypothalamic-pituitary-gonadal and hypothalamic-pituitary-adrenal axes of the european beaver (Castor fiber). Theriogenology 2017;87:266-75.  Back to cited text no. 50
Friedman JM. The function of leptin in nutrition, weight, and physiology. Nutr Rev 2002;60:S1-14.  Back to cited text no. 51
Seematter G, Guenat E, Schneiter P, Cayeux C, Jéquier E, Tappy L, et al. Effects of mental stress on insulin-mediated glucose metabolism and energy expenditure in lean and obese women. Am J Physiol Endocrinol Metab 2000;279:E799-805.  Back to cited text no. 52
Shiiya T, Nakazato M, Mizuta M, Date Y, Mondal MS, Tanaka M, et al. Plasma ghrelin levels in lean and obese humans and the effect of glucose on ghrelin secretion. J Clin Endocrinol Metab 2002;87:240-4.  Back to cited text no. 53
Simoens VL, Istók E, Hyttinen S, Hirvonen A, Näätänen R, Tervaniemi M, et al. Psychosocial stress attenuates general sound processing and duration change detection. Psychophysiology 2007;44:30-8.  Back to cited text no. 54