Ghrelin/obestatin ratio in two populations with low bodyweight: Constitutional thinness and anorexia nervosa

Germain, Natacha; Galusca, Bogdan; Grouselle, Dominique; Frère, Delphine; Tolle, Virginie; Zizzari, Philippe; Lang, François; Epelbaum, Jacques; Estour, Bruno

doi:10.1016/j.psyneuen.2008.10.001

Cited by 81 publications

(94 citation statements)

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“…Finally, those studies have been done on one time-point sampling contrary to our present circadian analysis, which could partly explain the discrepancy. Moreover, these data also strengthen previous results showing an orexigenic profile in AN, that might counteract the current restrictive eating behavior, in addition to already reported high ghrelin [31], low PYY [5], low leptin, and high 26Rfa [6]. This low level of IL-7 could be interpreted as a consequence of an adaptation mechanism in order to face the absence of food intake.…”

Section: Discussionsupporting

confidence: 89%

“…Samples were diluted 1:3. Assessment of other hormonal parameters was previously described [31]. Leptin was measured by RIA (Nichols Institute Diagnostics, San Juan Capistrano, CA, USA), normal values for a normal BMI (18–25) 3.7–11.1 mg / L); Cortisol by RIA (cortisol, Immunotech), coefficients of variation within and between test 7% and 8% respectively, detection limit 10 nmol / L, normal values (107 to 310 nmol / L); IGF1 by electrochemiluminescence on COBAS PLC; 17β estradiol by RIA (Dia Sorin, France), normal values during the follicular phase 30–50 ng / L; FSH and LH by IRMA (Beckman Coulter), normal values during the follicular phase 1.8–10.5 IU / L and 0.5–5 IU / L respectively; Testosterone by RIA (Beckman), extraction and chromatography, normal range 7–65 ng / dL; Free T3 by RIA (Beckman), normal values 2.5–5.8 pmol / L.…”

Section: Methodsmentioning

confidence: 99%

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Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

et al. 2016

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IntroductionInterleukin-7 (IL-7) is a cytokine involved in energy homeostasis as demonstrated in rodents. Anorexia nervosa is characterized by restrained eating behavior despite adaptive orexigenic regulation profile including high ghrelin plasma levels. Constitutional thinness is a physiological condition of resistance to weight gain with physiological anorexigenic profile including high Peptide YY plasma level. Healthy obesity can be considered as a physiological state of resistance to weight loss with opposite appetite regulating profile to constitutional thinness including low Peptide YY plasma level. No studies in IL-7 are yet available in those populations. Therefore we evaluated circadian plasma levels of IL-7 in anorexia nervosa compared to constitutional thinness, healthy obese and control females.Materials and Methods10 restrictive-type anorexia nervosa women, 5 bingeing/purging anorexia nervosa woman, 5 recovered restrictive anorexia nervosa women, 4 bulimic females, 10 constitutional thinness women, 7 healthy obese females, and 10 normal weight women controls were enrolled in this cross-sectional study, performed in endocrinology unit and academic laboratory. Twelve-point circadian profiles of plasma IL-7 levels were measured in each subject.Results24h mean IL-7 plasma levels (pg/ml, mean±SEM) were decreased in restrictive-type anorexia nervosa (123.4±14.4, p<0.0037), bingeing/purging anorexia nervosa (24.2±5.6, p<0.001), recovered restrictive anorexia nervosa (64.2±16.1, p = 0.01) and healthy obese patients (51±3.2, p<0.001) compared to controls (187.7±28.6). Bulimic patients (197.4±42.7) and constitutional thinness patients (264.3±35.8) were similar to controls.ConclusionsLow IL-7 is part of the adaptive profile in restrictive-type anorexia nervosa, confirming its difference with constitutional thinness. Healthy obesity, with low IL-7, is once again in mirror image of constitutional thinness with normal high IL-7.

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Section: Discussionsupporting

confidence: 89%

Section: Methodsmentioning

confidence: 99%

Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

et al. 2016

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“…Moreover, their relative proportions in tissues and plasma remained unclear. Previous studies using competitive immunoassays reported equimolar ratios of acyl ghrelin and obestatin in rat plasma (Zhang et al, 2005; Zizzari et al, 2007) consistent with a model previewing both peptides obtained by the processing of the same prohormone, while ratios of 2:1–4:1 were reported in humans (Germain et al, 2009, 2010). The reason for such discrepancy is unclear but this could evoke alternative splicing and/or different processing mechanism in rodents and humans.…”

Section: Discussionsupporting

confidence: 68%

Combination of Selective Immunoassays and Mass Spectrometry to Characterize Preproghrelin-Derived Peptides in Mouse Tissues

et al. 2017

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Preproghrelin is a prohormone producing several preproghrelin-derived peptides with structural and functional heterogeneity: acyl ghrelin (AG), desacyl ghrelin (DAG), and obestatin. The absence of selective and reliable assays to measure these peptides simultaneously in biological samples has been a limitation to assess their real proportions in tissues and plasma in physiological and pathological conditions. We aimed at reliably measure the ratio between the different preproghrelin-derived peptides in murine tissues using selective immunoassays combined with a highly sensitive mass spectrometry method. AG-, DAG-, and obestatin-immunopositive fractions from the gastrointestinal tract of adult wild-type and ghrelin-deficient mice were processed for analysis by mass spectrometry (MS) with a Triple Quadrupole mass spectrometer. We found that DAG was predominant in mouse plasma, however it only represented 50% of total ghrelin (AG+DAG) production in the stomach and duodenum. Obestatin plasma levels accounted for about 30% of all circulating preproghrelin-derived peptides, however, it represented <1% of total preproghrelin-derived peptides production (AG+DAG+Obestatin) in the stomach. Assays were validated in ghrelin-deficient mice since neither ghrelin nor obestatin immunoreactivities were detected in their stomach, duodenum nor plasma. MS analyses confirmed that obestatin-immunoreactivity in stomach corresponded to the C-terminal amidated form of the peptide but not to des(1–10)-obestatin, nor to obestatin-Gly. In conclusion, specificity of ghrelin and obestatin immunoreactivities in gastrointestinal tissues using selective immunoassays was validated by MS. Obestatin was less abundant than AG or DAG in these tissues. Whether this is due to inefficient processing rate of preproghrelin into mature obestatin in gastrointestinal mouse tissues remains elusive.

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“…Further studies have described a much higher level of acyl-ghrelin in anorexics than their BMI-matched control group 225-229,242,243. This indicates that persistent hyperghrelinemia possibly impairs ghrelin sensitivity and contributes to the pathogenesis of AN 91.…”

Section: Neuro-periphery Mechanisms Of Anorexia Nervosamentioning

confidence: 95%

Anorexia Nervosa: A Unified Neurological Perspective

Hasan¹,

Hasan²

2011

Int. J. Med. Sci.

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The roles of corticotrophin-releasing factor (CRF), opioid peptides, leptin and ghrelin in anorexia nervosa (AN) were discussed in this paper. CRF is the key mediator of the hypothalamo-pituitary-adrenal (HPA) axis and also acts at various other parts of the brain, such as the limbic system and the peripheral nervous system. CRF action is mediated through the CRF1 and CRF2 receptors, with both HPA axis-dependent and HPA axis-independent actions, where the latter shows nil involvement of the autonomic nervous system. CRF1 receptors mediate both the HPA axis-dependent and independent pathways through CRF, while the CRF2 receptors exclusively mediate the HPA axis-independent pathways through urocortin. Opioid peptides are involved in the adaptation and regulation of energy intake and utilization through reward-related behavior. Opioids play a role in the addictive component of AN, as described by the “auto-addiction opioids theory”. Their interactions have demonstrated the psychological aspect of AN and have shown to prevent the functioning of the physiological homeostasis. Important opioids involved are β-lipotropin, β-endorphin and dynorphin, which interact with both µ and κ opioids receptors to regulate reward-mediated behavior and describe the higher incidence of AN seen in females. Moreover, ghrelin is known as the “hunger” hormone and helps stimulate growth hormone (GH) and hepatic insulin-like-growth-factor-1(IGF-1), maintaining anabolism and preserving a lean body mass. In AN, high levels of GH due to GH resistance along with low levels of IGF-1 are observed. Leptin plays a role in suppressing appetite through the inhibition of neuropeptide Y gene. Moreover, the CRF, opioid, leptin and ghrelin mechanisms operate collectively at the HPA axis and express the physiological and psychological components of AN. Fear conditioning is an intricate learning process occurring at the level of the hippocampus, amygdala, lateral septum and the dorsal raphe by involving three distinct pathways, the HPA axis-independent pathway, hypercortisolemia and ghrelin. Opioids mediate CRF through noradrenergic stimulation in association with the locus coeruleus. Furthermore, CRF's inhibitory effect on gonadotropin releasing hormone can be further explained by the direct relationship seen between CRF and opioids. Low levels of gonadotropin have been demonstrated in AN where only estrogen has shown to mediate energy intake. In addition, estrogen is involved in regulating µ receptor concentrations, but in turn both CRF and opioids regulate estrogen. Moreover, opioids and leptin are both an effect of AN, while many studies have demonstrated a causal relationship between CRF and anorexic behavior. Moreover, leptin, estrogen and ghrelin play a role as predictors of survival in starvation. Since both leptin and estrogen are associated with higher levels of bone marrow fat they represent a longer survival than those who favor the ghrelin pathway. Future studies should consider cohort studies involving prepubertal males and females with high ...

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Ghrelin/obestatin ratio in two populations with low bodyweight: Constitutional thinness and anorexia nervosa

Cited by 81 publications

References 40 publications

Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

Interleukin-7 Plasma Levels in Human Differentiate Anorexia Nervosa, Constitutional Thinness and Healthy Obesity

Combination of Selective Immunoassays and Mass Spectrometry to Characterize Preproghrelin-Derived Peptides in Mouse Tissues

Anorexia Nervosa: A Unified Neurological Perspective

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