Effects of Isolation and Social Subchronic Stresses on Food Intake and Levels of Leptin, Ghrelin, and Glucose in Male Rats
Mina Sadat Izadi, Maryam Radahmadi, Maedeh Ghasemi, Atefeh Rayatpour
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan, Iran
|Date of Web Publication||29-Aug-2018|
Dr. Maryam Radahmadi
Department of Physiology, School of Medicine, Isfahan University of Medical Sciences, Isfahan
Source of Support: None, Conflict of Interest: None
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.
Keywords: Food intake, ghrelin, glucose, isolation stress, leptin, social stress
|How to cite this article:|
Izadi MS, Radahmadi M, Ghasemi M, Rayatpour A. Effects of Isolation and Social Subchronic Stresses on Food Intake and Levels of Leptin, Ghrelin, and Glucose in Male Rats. Adv Biomed Res 2018;7:118
|How to cite this URL:|
Izadi MS, Radahmadi M, Ghasemi M, Rayatpour A. Effects of Isolation and Social Subchronic Stresses on Food Intake and Levels of Leptin, Ghrelin, and Glucose in Male Rats. Adv Biomed Res [serial online] 2018 [cited 2019 Aug 19];7:118. Available from: http://www.advbiores.net/text.asp?2018/7/1/118/240076
| Introduction|| |
The balance between food intake and energy expenditure is regulated by the nervous system through complex mechanisms. Although several studies have been conducted to determine the complex arrays of internal and external factors that affect feeding, nutritional mechanisms are still in a state of ambiguity., In this regard, stress as an inseparable aspect of daily life has been known as a common external factor that can lead to physiological and behavioral impairments such as changes in the eating patterns., Stress responses are composed of a variety of replies originating from central and peripheral systems.
Obesity as a global concern results from physiological disturbances such as exposure to psychological stresses. It seems that the effective regulatory mechanisms of nutrition and stress are really important to be identified., An important issue in this regard is that stressful events can change the neuroendocrine signaling. Various hormonal and feeding biomarkers interactions regulate the feeding behavior in stressful situations. Some studies have shown that the feeding biomarkers (such as ghrelin, leptin, and glucose levels) have a key role in homeostasis and can regulate the food intake as peripheral responses.,,
Moreover, it has been demonstrated that various types and durations of stress lead to different physiological effects., As previous studies indicated, the type of stress plays a key role in determining the amount of food consumption., Furthermore, the duration of stress can change the feeding patterns., Based on the stress duration category, a variety of acute, subchronic, and chronic stress exists.,,,, Acute stress suppresses the appetite as an instant physiological response. While, seeking out and eating happens in the chronic stress situations., Furthermore, the amount of food intake is regulated by different mechanisms under various stress conditions.,,,,, In this regard, the effect of two common types of psychological stresses (social and isolation stress) in human societies on food intake and feeding biomarkers is still unknown. Today, the most influence of stress model on human societies is subchronic stress conditions. To the best of our knowledge, there was no exact evidence of the food intake changes in subchronic psychological stresses up to now. Hence, the present study was conducted to investigate the effects of two subchronic psychological stresses (social and isolation stress) on food intake, body weight, ghrelin, leptin, and glucose levels in rats.
| Materials and Methods|| |
In this work, 18 male Wistar rats were obtained from Pasteur Institute, Tehran, Iran, with an initial body weight of 200–250 g. Rats were housed under standard laboratory conditions; on a 12 h light/dark cycle at controlled temperature (22°C ± 2°C) and humidity (50% ± 5%) conditions with available food and water ad libitum. All the associated experiments were approved by the Research and Ethics Committee of Isfahan University of Medical Sciences in compliance with the international guiding principles for biomedical research involving animals in 1996 (NIH Publications No. 80–23, 1996 Rev).
Rats were randomly allocated to the following three groups (n = 6 in each group): Control (Co), social stress (SS), and isolation stress (IS) groups. Then, they were subjected to 7 days of subchronic social and isolation stresses.
To induce social stress, rats were transferred to the new cage with new neighbors for every 24 h as psychological stress. To induce isolation stress, rats were kept in individual cages without any other neighbors., Similarly, to induce social and isolation stresses, the rats were subjected to 7 days of subchronic social and isolation stresses.,,
Food intake paradigm
The simplest paradigm for investigating the food intake is to record the mass of food eaten during the fixed period. The stress lasted for 7 continuous days. For feeding measurements, the rats fasted for 16–18 h on day 7 of the experiment. At the end of experiments, on day 8, the rats were transported to the laboratory at least 1 h before the beginning of the feeding trial. The weight of food pellets was measured on an hourly basis and for a 3 h., Subsequently, the rat was individually placed in a transparent Plexiglas cage with a thick white paper lining at the bottom and allowed to have access to a premeasured amount of regular laboratory chow. Therefore, over three continuous hours, the rats were removed from the first test cage and placed into their new test cage after each hour., The amounts of food left in the first test cage, including crumbs, were measured and the amounts consumed were calculated. Furthermore, the feeding trials were done normally between 9:00 am and 12:00 on rats deprived of food for 16–18 h.
Measurement of body weight differences
Animal body weights were measured on days 1 and 7 of the experiment and the body weight differences (BWD = BWDay7−BWDay1) were evaluated.
Assessment of feeding biomarkers levels
In the current study, the levels of feeding biomarkers containing the serum levels of ghrelin and leptin as well as blood glucose level were measured. Hence, at the end of the experiments, day 8, rats were euthanized by light anesthesia. Tail blood sampling technique was used to collect blood (at the amount of 500 μl) from the rats at 8:00 to 9:00 am. On the fasting day, the blood glucose levels were measured using a glucometer (On Call Plus Co., USA). In addition, blood samples for hormonal analysis were collected in plastic vials and centrifuged at 6000 rpm for 20 min. Serums were separated from blood samples and stored at −80°C until hormones (the ghrelin and leptin) analysis. The commercial enzyme-linked immunosorbent assay kit (Zellbio Co., Germany) was used to assess the serum ghrelin and leptin levels.
The feeding study trials and other variables (e.g., levels of ghrelin, leptin, glucose and BWD) of the various groups (i.e., between-group comparisons) were compared using independent t-test. Furthermore, the repeated-measure ANOVA followed by least significant difference (LSD) post hoc test was used for food intake trend between experimental groups. The 3-h consecutive food consumption for comparing the food intake in 2 h (food intake of 1 vs. 2 h, 2 vs. 3 h, and 1 vs. 3 h) within the groups were analyzed using the paired Student's t-tests. Results are presented as mean ± standard error of the mean. The P < 0.05 was considered as statistically significant. Ultimately, the calculations were performed using SPSS 21 (SPSS Inc., Chicago, IL, USA).
| Results|| |
Effects of subchronic stresses on food intake of three continuous hours
Statistical analysis on the food intake of three continuous hours revealed that the food intake significantly (P < 0.05) reduced at the 1st h of measurement in the subchronic SS group compared to the Co group. Furthermore, the consumption of food intake in the subchronic IS group significantly (P < 0.001 and P = 0.01; respectively) decreased in the 2nd h compared to the Co and SS groups. In addition, the food intake changes at the 3rd h showed no significant reduction in both SS and IS groups [Figure 1].
|Figure 1: Comparison of the food intake (g) in the experimental groups after 1, 2, and 3 h. Results are expressed as mean ± standard error of mean (independent samples t- test). * P < 0.05 and ***P < 0.001 compared to control group, €€P < 0.01 compared to social stress group|
Click here to view
Effects of subchronic stresses on cumulative food intake
The results show a decline of cumulative food intake in both IS and SS groups. Moreover, the cumulative food intake significantly (P < 0.05) showed a reduction only in the IS group compared to the Co group [Figure 2].
|Figure 2: Comparison of the cumulative food intake (g) in the experimental groups. Results are expressed as mean ± standard error of mean (independent samples t- test). *P < 0.05 compared to control group|
Click here to view
Effects of subchronic stresses on food intake trend
Based on the repeated mature ANOVA and post hoc LSD's results, there was a statistically significant (P < 0.05) difference in the IS group when compared with the Co group [Figure 3].
|Figure 3: Comparison of the 3-h food intake trend (three continuous hours) in the experimental groups; results are expressed as a mean ± standard error of the mean (repeated measure one-way ANOVA followed by least significant difference's post hoc test and paired Student's t-test for comparing of the food intake in comparison of 2 h in each group). ℓP = 0.05, ℓℓP = 0.01, and ℓℓℓP = 0.001 food intake value in 1 versus 2 h; ◻P = 0.05 food intake value in 2 versus 3 h; ++P = 0.01 and +++P = 0.001 food intake value in 1 versus 3 h|
Click here to view
Food intake of all three trials (i.e., 1 vs. 2 h, 2 vs. 3 h, and 1 vs. 3 h) was analyzed by the paired Student's t-tests [Figure 3]. The analyses revealed statistically significant differences in food intake 1 vs. 2 h, 2 vs. 3 h, and 1 vs. 3 h in the experimental groups [Figure 3].
The food intake of paired trials 1 vs. 2 h in the Co, SS, and IS groups showed significant (P < 0.01, P < 0.05, and P < 0.001, respectively) decreases [Figure 3]. In these groups, comparison of food intake of 2 h vs. 3 h showed statistically significant (P < 0.05) decreases only in the IS group [Figure 3]. Furthermore, in the Co, SS, and IS groups, the food intake of 1 h vs. 3 h showed significant (P < 0.01, P < 0.01, and P < 0.001, respectively) decreases [Figure 3].
Measurement of body weight differences
A declined food intake trend and body weight drop appeared in both SS and IS groups [Figure 4]. Although a slight body weight was gained in the Co group, the body weights were decreased in both subchronic IS and SS groups.
|Figure 4: Comparison of the body weight differences (g) in the experimental groups. Results are expressed as mean ± standard error of mean (independent samples t-test). *P = 0.05 compared to control group|
Click here to view
The results indicated no statistically significant difference between the SS and Co groups with regard to the BWD [Figure 4].
As shown in [Figure 4], the BWD was significantly (P < 0.05) lower in the IS group compared to the Co group.
Assessment of feeding biomarkers levels
The serum ghrelin level significantly (P < 0.05) decreased in the IS group compared to the Co group. Furthermore, a slight or no significant reduction was observed in the SS group [Figure 5]a.
|Figure 5: Comparison of (a) the serum ghrelin level (ng/ml), (b) the serum leptin level (ng/ml), and (c) the blood glucose levels (mg/ml) in the experimental groups. Results are expressed as the mean ± standard error of the mean (independent samples t- test). *P = 0.05 compared to control group|
Click here to view
The serum leptin level did not show a statistically significant increase (P > 0.05) in the IS group while in the SS group, the serum leptin level was similar to the Co group [Figure 5]b.
As can be noted, the blood glucose had no significant increases in both the SS and IS groups compared to the Co group, suggesting partial hyperglycemia in both SS and IS groups [Figure 5]c.
| Discussion|| |
The effect of subchronic psychological stress was not clear on the food intake and feeding biomarkers such as levels of leptin, ghrelin, and glucose. Hence, the present study evaluated whether two types of subchronic (social and isolation) stresses could be mediated through the changes of serum levels ghrelin and leptin as well as blood glucose level on the energy homeostasis (food intake) and body weight.
According to the results of the current study, the amount of food intake decreased in subchronic social and particularly isolation stress groups [Figure 1] and [Figure 2], as a declining food intake trend was observed in both these groups [Figure 3]. Furthermore, BWD followed the feeding behavior in the subchronic stress conditions [Figure 4]. It is possible that the body weight loss resulted in the reduction in food intake and enhancement probably of body metabolism in subchronic stress conditions. Some animals and humans studies demonstrated that the food intake either increases or decreases in response to the different kinds of stress.,,, Previous studies have identified various aspects of feeding behaviors including the increase in food intake in repeated restraint stress, the body weight loss in an inescapable shock condition, and anorexia in immobilization stress.,, According to Ranjbar et al., stress is divided into different subsets based on the duration of acute stress, subchronic stress (mid stress), and chronic stress. They demonstrated that subchronic stress (7 days) has the most deleterious emotional stress.,, In this regard, previous studies also have shown that acute stress is associated with the reduction of food intake,, while chronic stress increases the food consumption. Moreover, it seems that changes of food intake are related to the stressor's characteristics such as type stress, duration of stress, the intensity of stress, and the individual's stress characteristics, metabolic state, and dietary in stress condition.,, Furthermore, Ranjbar et al. reported the effect of three durations (1, 7, and 21 days) of restraint stress including acute, subchronic, and chronic stresses on the alternations of BWD. Moreover, they proposed that there were more changes in subchronic restraint stress on BWD. Collectively, the findings of the current and previous studies suggested that stress duration (even with different kinds of stress) is the main factor that affects the BWD. In addition, it is proposed that the subchronic stress corresponds to the alternation of food intake responses similar to acute stress and reduces food intake and body weight.
Another finding of this study is that the serum ghrelin level significantly decreased in isolation stress groups, although this reduction was not statistically significant in the subchronic social stress [Figure 5]a. Consistent with these data, Currie et al. reported some interactions between ghrelin and corticotropin-releasing (CRH) hormone for controlling of the neural circuits of stress and feeding behaviors. Since the ghrelin plays an important role in adjusting hypothalamic–pituitary–adrenal (HPA) axis, the potential role was considered for ghrelin as a stress feedback signal. In this connection, Saegusa et al. reported that the serum ghrelin level decreased after 7 days of novelty stress. They suggested the increases in CRH resulted in a declined ghrelin level, leading to the sustained food intake reduction. However, other researches indicated an opposite finding between the ghrelin level and food intake.,, Some previous studies demonstrated that the elevated serum ghrelin level helps to an individual for adaptation to chronic stress but at the expense of increased eating food. Therefore, it is possible that subchronic isolation stress suppresses appetite and food consumption by the reduction of serum ghrelin level in the current study.
According to other data presented in this work, the serum leptin level showed no significant increase in subchronic social and isolation stress groups [Figure 5]b. In contrast, Ortolani et al. showed that the anorexigenic effect of footshock stress is irrelevant to leptin serum elevation. Meanwhile, Bernier et al. reported that leptin regulates the food intake in hypoxic stress. Furthermore, another study reported that leptin decreased the food consumption by inhibition of orexigenic signals like NPY and agouti-related peptide as well as the expression of the anorexigenic signals such as proopiomelanocortin., Nevertheless, according to a previous study, the changes in the leptin level (as a regulatory link between energy homeostasis and the HPA function) depend on various factors such as different psychological stressors.,
We found a nonsignificant hyperglycemia in both subchronic stress groups [Figure 5]c. In contrast, some studies demonstrated sympathetic and/or glucocorticoids activation can increase the blood glucose under acute stress conditions., Furthermore, Shiiya et al. reported that the elevated blood glucose level can decrease the serum ghrelin level. Moreover, in the present study, the changes in leptin and glucose levels were in line with other studies, but statistically nonsignificant. Therefore, based on the results of the present study, it is logical to expect that the slightly and nonsignificantly elevated serum leptin and blood glucose levels may have a contributory role on the decrease in ghrelin level for anorectic effects in the subchronic stress conditions. These differences depend on the ability to adapt to stress; an ability that is related to sex, age, genetic makeup, stress duration, and environmental influences.
| Conclusions|| |
Subchronic isolation stress seems to be more destructive with respect to subchronic social stress on food intake reduction. In addition, it is possible that the reduced food intake and body weight loss result in the decreased serum ghrelin level, but not the elevated serum leptin and blood glucose levels in subchronic stress conditions. Nevertheless, these factors may help decrease the ghrelin level for anorectic effects in the subchronic stress conditions. Accordingly, further studies need to be carried out to clarify the neuronal pathways by which psychological stresses exert either inhibitory or stimulatory effects on food intake as a function of time.
Conduction of the present research was made possible through the supports received from Isfahan University of Medical Sciences, Isfahan, Iran.
Financial support and sponsorship
This study was funded by Isfahan University of Medical Sciences grant number 396593.
Conflicts of interest
There are no conflicts of interest.
| References|| |
Spiegelman BM, Flier JS. Obesity and the regulation of energy balance. Cell 2001;104:531-43.
Sobrino Crespo C, Perianes Cachero A, Puebla Jiménez L, Barrios V, Arilla Ferreiro E. Peptides and food intake. Front Endocrinol (Lausanne) 2014;5:58.
Spencer SJ. Perinatal programming of neuroendocrine mechanisms connecting feeding behavior and stress. Front Neurosci 2013;7:109.
Torres SJ, Nowson CA. Relationship between stress, eating behavior, and obesity. Nutrition 2007;23:887-94.
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.
Adam TC, Epel ES. Stress, eating and the reward system. Physiol Behav 2007;91:449-58.
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.
Chen Y. Regulation of food intake and the development of anti-obesity drugs. Drug Discov Ther 2016;10:62-73.
Fischer EK, O'Connell LA. Modification of feeding circuits in the evolution of social behavior. J Exp Biol 2017;220:92-102.
Farr OM, Li CS, Mantzoros CS. Central nervous system regulation of eating: Insights from human brain imaging. Metabolism 2016;65:699-713.
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.
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.
Rabasa C, Dickson SL. Impact of stress on metabolism and energy balance. Curr Opin Behav Sci 2016;9:71-7.
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.
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.
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.
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.
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.
Oliver G, Wardle J, Gibson EL. Stress and food choice: A laboratory study. Psychosom Med 2000;62:853-65.
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.
Ulrich-Lai YM, Fulton S, Wilson M, Petrovich G, Rinaman L. Stress exposure, food intake and emotional state. Stress 2015;18:381-99.
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.
la Fleur SE. The effects of glucocorticoids on feeding behavior in rats. Physiol Behav 2006;89:110-4.
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.
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.
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.
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.
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.
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.
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.
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.
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.
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.
Dallman MF. Stress-induced obesity and the emotional nervous system. Trends Endocrinol Metab 2010;21:159-65.
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.
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.
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.
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.
Bazhan N, Zelena D. Food-intake regulation during stress by the hypothalamo-pituitary-adrenal axis. Brain Res Bull 2013;95:46-53.
Sominsky L, Spencer SJ. Eating behavior and stress: A pathway to obesity. Front Psychol 2014;5:434.
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.
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.
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.
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.
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.
Uchida A, Zigman JM, Perelló M. Ghrelin and eating behavior: Evidence and insights from genetically-modified mouse models. Front Neurosci 2013;7:121.
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.
Myers MG, Cowley MA, Münzberg H. Mechanisms of leptin action and leptin resistance. Annu Rev Physiol 2008;70:537-56.
Ahima RS, Flier JS. Leptin. Annu Rev Physiol 2000;62:413-37.
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.
Friedman JM. The function of leptin in nutrition, weight, and physiology. Nutr Rev 2002;60:S1-14.
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.
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.
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.
[Figure 1], [Figure 2], [Figure 3], [Figure 4], [Figure 5]