Gender Differences in Ghrelin Response to Chronic Immobilization Stress in Rats: Possible Role of Estrogen

Elbassuoni, Eman

doi:10.4149/gpb_2013061

Cited by 13 publications

(5 citation statements)

References 73 publications

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“…The authors postulated that menopausal status could potentially affect bariatric surgery outcome in a procedure-dependent manner. Translational research using animal models suggests that absence of oestrogen alters ghrelin responses [ 35 ], which could potentially explain the altered effects of SG in women who are over the age of 50. Interestingly, in men, weight outcomes with SG improved relative to RYGBP with increasing age, suggesting that a sex-specific factor is important for SG response.…”

Section: Discussionmentioning

confidence: 99%

Age- and sex-specific effects on weight loss outcomes in a comparison of sleeve gastrectomy and Roux-en-Y gastric bypass: a retrospective cohort study

et al. 2014

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BackgroundRoux-en-Y gastric bypass (RYGBP) and sleeve gastrectomy (SG) are the most common bariatric procedures undertaken globally but there are no evidenced-based criteria that inform the selection of one operation over the other. The purpose of this study was thus to compare weight loss outcomes between RYGBP and SG, and to define patient factors affecting weight loss.MethodsA single-centre two-year follow-up retrospective cohort study of all adults who underwent either RYGBP (n = 422) or SG (n = 432) between 2007 and 2012, at University College London Hospitals National Health Service Foundation Trust, an academic tertiary referral centre, was undertaken. Multilevel linear regression was used to compare weight loss between groups, enabling adjustment for preoperative BMI (body mass index) and evaluation for interaction factors.ResultsOne- and two-year results showed that unadjusted BMI loss was similar between groups; 13.7 kg/m2 (95% CI: 12.9, 14.6 kg/m2) and 12.8 kg/m2 (95% CI: 11.8, 13.9 kg/m2) for RYGBP patients respectively compared with 13.3 kg/m2 (95% CI: 12.0, 14.6 kg/m2) and 11.5 kg/m2 (95% CI: 10.1, 13.0 kg/m2) for SG patients respectively. Adjusting for preoperative BMI, there was 2.2 kg/m2 (95% CI: 1.5, 2.8) and 2.3 kg/m2 (95% CI: 1.3, 3.3) greater BMI loss in the RYGBP group compared to the SG group at one and two years respectively (P < 0.001 for both). The interaction analyses demonstrated that age and sex had important differential impacts on SG and RYGBP weight outcomes. Men under 40 and women over 50 years obtained on average far less benefit from SG compared to RYGBP, whereas men over 40 years and women under 50 years experienced similar weight loss with either procedure (P = 0.001 and 0.022 for interaction effects at one and two years respectively).ConclusionsOur results show that patient sex and age significantly impact on weight loss in a procedure-dependent manner and should be considered when choosing between RYGBP and SG. Optimizing procedure selection could enhance the effectiveness of bariatric surgery, thus further increasing the benefit-to-risk ratio of this highly effective intervention.Electronic supplementary materialThe online version of this article (doi:10.1186/2052-9538-1-12) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Age- and sex-specific effects on weight loss outcomes in a comparison of sleeve gastrectomy and Roux-en-Y gastric bypass: a retrospective cohort study

et al. 2014

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“…Early life stress induced by limited access to bedding and nesting material for a week led to attenuated weight gain during stress exposure in male and female pups, which was compensated by an increased weight gain after termination of the stress exposure (Yam et al, 2017). As an exception, only one study found increased food intake and body weight gain during immobilization stress over a period of three weeks, which was more pronounced in male than female rats (Elbassuoni, 2014).…”

Section: Effects Of Stress On Food Intake and Body Weight In Rodents mentioning

confidence: 99%

“…Similarly, chronic mild unpredictable stress (CUMS) protocols were shown to induce elevated total serum ghrelin levels in rats (Lopez Lopez et al, 2018) and plasma AG levels in mice (Patterson et al, 2010;Huang et al, 2017). Also chronic immobilization stress increased ghrelin or AG levels in rats (Elbassuoni, 2014;Meyer et al, 2014). A recent study showed that elevated plasma AG levels following chronic immobilization stress in adolescent rats persisted up to four months after stress exposure (Yousufzai et al, 2018).…”

Section: Effects Of Stress On Plasma Ghrelin Levels In Rodentsmentioning

confidence: 99%

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

Fritz

Singewald

Bundel

2020

Front. Synaptic Neurosci.

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Ghrelin is a peptide hormone released by specialized X/A cells in the stomach and activated by acylation. Following its secretion, it binds to ghrelin receptors in the periphery to regulate energy balance, but it also acts on the central nervous system where it induces a potent orexigenic effect. Several types of stressors have been shown to stimulate ghrelin release in rodents, including nutritional stressors like food deprivation, but also physical and psychological stressors such as foot shocks, social defeat, forced immobilization or chronic unpredictable mild stress. The mechanism through which these stressors drive ghrelin release from the stomach lining remains unknown and, to date, the resulting consequences of ghrelin release for stress coping remain poorly understood. Indeed, ghrelin has been proposed to act as a stress hormone that reduces fear, anxiety-and depression-like behaviors in rodents but some studies suggest that ghrelin may-in contrast-promote such behaviors. In this review, we aim to provide a comprehensive overview of the literature on the role of the ghrelin system in stress coping. We discuss whether ghrelin release is more than a byproduct of disrupted energy homeostasis following stress exposure. Furthermore, we explore the notion that ghrelin receptor signaling in the brain may have effects independent of circulating ghrelin and in what way this might influence stress coping in rodents. Finally, we examine how the ghrelin system could be utilized as a therapeutic avenue in stressrelated psychiatric disorders (with a focus on anxiety-and trauma-related disorders), for example to develop novel biomarkers for a better diagnosis or new interventions to tackle relapse or treatment resistance in patients.

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“…We found that lack of gonadal steroids in ORX males did not have any effect on ghrelin levels, whereas serum ghrelin levels in OVX females were drastically reduced and indistinguishable from ghrelin levels found in males. While a previous study indicated a similar effect of gonadectomy ( 35 ), also the opposite has been reported ( 21 , 36 ). Matsubara et al.…”

Section: Discussionmentioning

confidence: 64%

From an Empty Stomach to Anxiolysis: Molecular and Behavioral Assessment of Sex Differences in the Ghrelin Axis of Rats

et al. 2022

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Ghrelin, a stomach-produced hormone, is well-recognized for its role in promoting feeding, controlling energy homeostasis, and glucoregulation. Ghrelin’s function to ensure survival extends beyond that: its release parallels that of corticosterone, and ghrelin administration and fasting have an anxiolytic and antidepressant effect. This clearly suggests a role in stress and anxiety. However, most studies of ghrelin’s effects on anxiety have been conducted exclusively on male rodents. Here, we hypothesize that female rats are wired for higher ghrelin sensitivity compared to males. To test this, we systematically compared components of the ghrelin axis between male and female Sprague Dawley rats. Next, we evaluated whether anxiety-like behavior and feeding response to endogenous or exogenous ghrelin are sex divergent. In line with our hypothesis, we show that female rats have higher serum levels of ghrelin and lower levels of the endogenous antagonist LEAP-2, compared to males. Furthermore, circulating ghrelin levels were partly dependent on estradiol; ovariectomy drastically reduced circulating ghrelin levels, which were partly restored by estradiol replacement. In contrast, orchiectomy did not affect circulating plasma ghrelin. Additionally, females expressed higher levels of the endogenous ghrelin receptor GHSR1A in brain areas involved in feeding and anxiety: the lateral hypothalamus, hippocampus, and amygdala. Moreover, overnight fasting increased GHSR1A expression in the amygdala of females, but not males. To evaluate the behavioral consequences of these molecular differences, male and female rats were tested in the elevated plus maze (EPM), open field (OF), and acoustic startle response (ASR) after three complementary ghrelin manipulations: increased endogenous ghrelin levels through overnight fasting, systemic administration of ghrelin, or blockade of fasting-induced ghrelin signaling with a GHSR1A antagonist. Here, females exhibited a stronger anxiolytic response to fasting and ghrelin in the ASR, in line with our findings of sex differences in the ghrelin axis. Most importantly, after GHSR1A antagonist treatment, females but not males displayed an anxiogenic response in the ASR, and a more pronounced anxiogenesis in the EPM and OF compared to males. Collectively, female rats are wired for higher sensitivity to fasting-induced anxiolytic ghrelin signaling. Further, the sex differences in the ghrelin axis are modulated, at least partly, by gonadal steroids, specifically estradiol. Overall, ghrelin plays a more prominent role in the regulation of anxiety-like behavior of female rats.

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Gender Differences in Ghrelin Response to Chronic Immobilization Stress in Rats: Possible Role of Estrogen

Cited by 13 publications

References 73 publications

Age- and sex-specific effects on weight loss outcomes in a comparison of sleeve gastrectomy and Roux-en-Y gastric bypass: a retrospective cohort study

Age- and sex-specific effects on weight loss outcomes in a comparison of sleeve gastrectomy and Roux-en-Y gastric bypass: a retrospective cohort study

The Good, the Bad and the Unknown Aspects of Ghrelin in Stress Coping and Stress-Related Psychiatric Disorders

From an Empty Stomach to Anxiolysis: Molecular and Behavioral Assessment of Sex Differences in the Ghrelin Axis of Rats

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