Is association between thyroid hormones and gut peptides, ghrelin and obestatin, able to suggest new regulatory relation between the HPT axis and gut?

doi:10.1016/j.regpep.2014.01.001

Regulatory Peptides

Volume 189, 10 February 2014, Pages 17-21

https://doi.org/10.1016/j.regpep.2014.01.001 Get rights and content

Highlights

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Ghrelin and obestatin levels were decreased in subclinical hypothyroidism.
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Ghrelin and obestatin levels were increased in subclinical hyperthyroidism.
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Ghrelin and obestatin levels were significantly correlated with TSH, FT3 and FT4.
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We conclude that changes of TSH, FT3 and FT4 are associated with gut hormone levels.
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New regulatory relation between the HPT axis and gut

Abstract

Background

Ghrelin and obestatin are important appetite- and energy-regulating peptides, secreted by the stomach. These gut peptides and thyroid hormones are involved in metabolism regulation. Although subclinical thyroidism is common, to date, very few studies have been reported about gut hormones in thyroid dysfunction, and their results are controversial. The purpose of this study was to investigate ghrelin and obestatin in patients with subclinical hypo- and hyperthyroidism. Moreover, is association between thyroid hormones and gut peptides able to suggest new regulatory relation between the HPT axis and gut?

Materials and methods

The study group included 70 subclinical hypo- and hyperthyroid subjects (in equal groups) and 35 healthy euthyroid controls. Serum values of ghrelin, obestatin, free T3, free T4, thyroid-stimulating hormone and the ratio of ghrelin to obestatin were measured in all participants.

Results

Ghrelin and obestatin both decreased in subclinical hypothyroid subjects (320 ± 81 ng/l and 44.3 ± 11.7 ng/l, respectively) compared to the control group (487 ± 110 ng/l and 58.5 ± 10.3 ng/l, respectively). On the other hand, ghrelin and obestatin both increased in subclinical hyperthyroid subjects (750 ± 289 ng/l and 71.1 ± 27.3 ng/l, respectively) compared to the control group. In addition, ghrelin and obestatin showed strong correlations with TSH, FT3 and FT4.

Conclusion

This study shows that gut hormones are significantly associated with thyroid hormones. Thus, there may be a cross talk between the HPT axis and gut. We would like to consider new regulatory relation for description of the found data.

Introduction

Three peptides are produced by ghrelin gene: acyl ghrelin, des-acyl ghrelin and obestatin; all may be part of a complex system with multiple elements that comprise the center of an integrated gut–brain axis that modulates appetite, digestion, gut motility, adiposity and energy partition [1], [2]. Ghrelin is a gastrointestinal peptide produced by the stomach, and the endogenous ligand for the growth hormone secretagouge receptor (GHSR) [3], [4]. In the energy balance and regulation of body weight, ghrelin plays an important role with orexigenic properties. It increases food intake, weight gain and adipogenesis [5], [6], [7]. Obestatin is an anorexigenic gut-peptide hormone that is generated by way of post-translational modification of preproghrelin, and secreted by the stomach [8]. This ghrelin-associated peptide functions by inhibiting appetite, slowing down gastric emptying, decreasing body weight gain and controlling energy expenditure [9], [10], [11]. Obestatin is capable of binding to GPR39 (G protein-coupled receptor 39) to regulate the functions of gastrointestinal tissue [12]. Furthermore, the two gut peptides have been investigated in several pathologies, including obesity, anorexia nervosa (AN) and diabetes [10], [13], [14], [15].

Hypothalamus–pituitary–thyroid (HPT) axis is also associated with metabolic changes that affect body mass, appetite, basal metabolic rate and energy balance. Thyroid diseases are among the most common endocrinological disorders [16]. Hypothyroidism is related to weight gain, decreased appetite and basal metabolic rate, whereas hyperthyroidism is related with weight loss, increased appetite and metabolic rate [17], [18].

The peripheral hormones ghrelin, obestatin and thyroid play integrated regulatory roles in and provide feedback information on the nutritional and energetic status of the body. These hormones modulate central pathways in the brain, including the hypothalamus, to influence food intake, energy expenditure and to maintain energy homeostasis [9], [19], [20]. Moreover, the association between changes in thyroid state and variations in circulating gut hormones is unsettled, due to the paucity of available studies and the conflicting results [21], [22], [23]. Therefore, it seems rational to investigate potential interactions between gut peptides and thyroid hormones.

The main objective of the study was to determine serum ghrelin and obestatin levels in different states of thyroid function. The second was to reveal correlations of gut and thyroid hormones. In addition, we hypothesize that there may be new regulatory relation between the hypothalamus–pituitary–thyroid axis and gut.

Section snippets

Subjects and study design

The study groups were the following: 35 hypothyroid (females/males ratio 22:13), 35 hyperthyroid subjects and 35 healthy euthyroid volunteers (2.0 < serum TSH level < 4.5 mIU/l) served as the control group. All of them recruited from the outpatient clinic of Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. The diagnosis of thyroid dysfunction was based on clinical assessment and biochemical findings. The study was performed at the time of

Results

The main demographic, anthropometric, clinical and biochemical characteristics of the participants are presented in Table 1. The patients and control subjects were well matched in age, sex and BMI parameters.

Discussion

This is the first study to show that gut hormone concentrations were markedly changed in subclinical hypo- and hyperthyroidism, as well as changing the ghrelin to obestatin ratio. Furthermore, we observed significant correlations of ghrelin and obestatin with TSH, FT3 and FT4 (Table 2). As a result, gut peptides and thyroid hormones are considerably associated and there may be regulatory interactions between them.

There are few studies regarding the association of ghrelin and/or obestatin with

Conclusion

In conclusion, our study showed that gut hormones are significantly associated with thyroid hormones. Thus, there may be a cross talk between the HPT axis and gut. We would like to consider new regulatory relation for description of the found data. Of course further studies are necessary to confirm the considering suggested relation and probable mechanism(s).

Acknowledgment

This work was supported by a financial grant from the Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Iran. We sincerely acknowledge all participants and those who assisted in this study.

References (38)

A. Abizaid et al.
Brain circuits regulating energy homeostasis
Regul Pept
(2008)
J. Epelbaum et al.
Role of the ghrelin/obestatin balance in the regulation of neuroendocrine circuits controlling body composition and energy homeostasis
Mol Cell Endocrinol
(Jan 27, 2010)
A.J. Ren et al.
Obestatin, obesity and diabetes
Peptides
(Feb 2009)
A. Stengel et al.
Ghrelin, des-acyl ghrelin and nesfatin-1 in gastric X/A-like cells: role as regulators of food intake and body weight
Peptides
(Feb 2010)
N. Germain et al.
Ghrelin/obestatin ratio in two populations with low bodyweight: constitutional thinness and anorexia nervosa
Psychoneuroendocrinology
(Apr 2009)
P. Iglesias et al.
Influence of thyroid dysfunction on serum concentrations of adipocytokines
Cytokine
(Nov 2007)
N. Zhang et al.
Meta-analysis of the relationship between obestatin and ghrelin levels and the ghrelin/obestatin ratio with respect to obesity
Am J Med Sci
(Jan 2011)
C.Y. Chen et al.
Ghrelin gene products and the regulation of food intake and gut motility
Pharmacol Rev
(2009)
M.T. Bluet-Pajot et al.
A striking example of neuroendocrine peptide pleiotropy
Med Sci (Paris)
(Aug–Sep 2005)
M. Kojima et al.
Ghrelin is a growth-hormone-releasing acylated peptide from stomach
Nature
(Dec 9, 1999)

R. Hassouna et al.

The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake

J Neuroendocrinol

(Jul 2010)

C.L. Boguszewski et al.

Neuroendocrine body weight regulation: integration between fat tissue, gastrointestinal tract, and the brain

Endokrynol Pol

(Mar–Apr 2010)

I.D. Majumdara et al.

Gastrointestinal regulatory peptides and their effects on fat tissue

Curr Opin Endocrinol Diabetes Obes

(Feb 2010)

J.V. Zhang et al.

Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake

Science

(Nov 11, 2005)

J.V. Zhang et al.

Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39

Mol Endocrinol

(Jun 2008)

V. Vicennati et al.

Circulating obestatin levels and the ghrelin/obestatin ratio in obese women

Eur J Endocrinol

(Sep 2007)

S.A. Katergari et al.

Ghrelin in pathological conditions

Endocr J

(Jul 2008)

M. Gunduz et al.

Role of surrogate markers of atherosclerosis in clinical and subclinical thyroidism

Int J Endocrinol

(2012)

M.I. Surks et al.

Subclinical thyroid disease: scientific review and guidelines for diagnosis and management

JAMA

(Jan 14, 2004)

Cited by (24)

Levothyroxine dose adjustment in hypothyroid patients following gastric sleeve surgery
2020, Annales d'Endocrinologie
Citation Excerpt :
A decrease in ghrelin is observed after by-pass and sleeve gastrectomy [32] as it is mainly secreted in the gastric fundus, which is removed by this surgery. Ghrelin has appetite stimulating properties and also plays a role in thyroid function: Emami et al. showed a negative correlation between ghrelin and TSH and a positive correlation between ghrelin and T4 and T3 in both hypothyroid and hyperthyroid patients [33]. A two-way regulation between the hypothalamic-pituitary and peptides secreted by the digestive system appears to exist, although mechanisms have not yet been elucidated [32].
Euthyroid patients show decreased TSH level following sleeve gastrectomy. However, studies of levothyroxine absorption after bariatric surgery reported contradictory results and data on levothyroxine dose adjustment according to weight are sparse. The aim of this study was to evaluate levothyroxine dose adjustment during weight loss following sleeve surgery.
This retrospective study assessed change in levothyroxine dose in patients undergoing sleeve gastrectomy at the university hospital center of Nîmes (France) between January 2010 and March 2016. Patients were receiving standard bariatric surgery follow-up with levothyroxine therapy for hypothyroidism.
Fifty-two of the 271 patients who underwent sleeve gastrectomy (19.2%) were being treated with levothyroxine. Among these patients, 31 were followed up for 12 months, including 12 who were followed up for 24 months. Mean weight loss was 35 ± 11 kg at 12 months and 41.8 ± 10.2 kg at 24 months. Daily levothyroxine dose decreased from 108 [88–144] μg/day to 94 [63–125] μg/day at 12 months and 69 [44–134] μg/day at 24 months, with positive correlation between dose and weight loss at 12 months (P = 0.03). Weight-adjusted dose was 1.04 [0.81–1.24] μg/kg/day at baseline, 1.14 [0.85–1.66] μg/kg/day at 12 months, and 0.85 [0.53–2.10] μg/kg/day at 24 months, showing no correlation with weight loss. Median TSH level dropped to 1.30 [0.63–2.27] mIU/l at 12 months and 1.48 [1.08–2.42] mIU/l at 24 months.
Despite a decrease in daily levothyroxine dose correlating with weight loss at 12 months, the absence of correlation with weight-adjusted dose suggests the involvement of confounding factors such as poor levothyroxine absorption or altered thyroid function. Further studies are required to elucidate the absorption of levothyroxine.
Les patients euthyroïdiens présentent un niveau de thyréostimuline (TSH) diminué après une gastrectomie longitudinale. Cependant, des études sur l’absorption de la Lévothyroxine après une chirurgie de l’obésité rapportent des résultats contradictoires et les données sur l’ajustement de la dose de lévothyroxine en fonction du poids sont éparses. L’objectif de cette étude est d’évaluer l’ajustement de la dose de lévothyroxine au cours de la perte de poids qui suit la gastrectomie longitudinale.
Cette étude rétrospective évalue les changements de doses de la lévothyroxine chez les patients bénéficiant d’une gastrectomie longitudinale au centre hospitalier universitaire de Nîmes (France) entre janvier 2010 et mars 2016. Les patients ont reçu un suivi post-opératoire standard après une chirurgie de l’obésité ainsi qu’un traitement à la lévothyroxine pour l’hypothyroïdie.
Cinquante-deux des 271 patients ayant bénéficié d’une gastrectomie longitudinale (19,2 %) ont été traités avec de la lévothyroxine. Parmi ces patients 31 ont été suivis pendant 12 mois dont 12 avec un suivi de 24 mois. La perte de poids moyenne était de 35 ± 11 kg à 12 mois et de 41,8 ± 10,2 kg à 24 mois. La dose quotidienne de lévothyroxine a été diminuée de 108 [88–144] μg/jour à 94 [63–125] μg/jour à 12 mois puis, à 69 [44–134] μg/jour à 24 mois, avec une corrélation positive entre la dose de lévothyroxine et la perte de poids à 12 mois (p = 0,03). La dose ajustée en fonction du poids était de 1,04 [0,81–1,24] μg/kg/jour au début de l’étude, de 1,14 [0,85–1,66] μg/kg/jour à 12 mois et de 0,85 [0,53–2,10] μg/kg/jour à 24 mois, ne montrant aucune corrélation avec la perte de poids. La médiane du niveau de TSH a diminué jusqu’à 1,30 [0,63–2,27] mUI/L à 12 mois puis 1,48 [1,08–2,42] mUI/L à 24 mois.
Malgré une corrélation entre la diminution des doses quotidiennes de lévothyroxine et la perte de poids à 12 mois, l’absence de corrélation entre la perte de poids et les doses ajustées en fonction du poids suggère la présence de facteurs confondants tels qu’une faible absorption de la lévothyroxine ou un fonctionnement altéré de la thyroïde. Des études plus poussées sont nécessaires afin de mieux comprendre l’absorption de la lévothyroxine.
Thyroid function before and after Roux-en-Y gastric bypass: an observational study
2020, Surgery for Obesity and Related Diseases
Citation Excerpt :
However, this mechanism does not fully explain the reduction in TSH. Some intestinal peptides have been studied to find new regulatory pathways of the hypothalamic-pituitary-thyroid axis, such as ghrelin, obestatin, and glucagon-like protein 1 (GLP-1), as well as activation of the G- protein-coupled bile acid receptor 5 membrane receptor by increasing bile acids [16,37]. RYGB promotes major changes in intestinal hormones.
Population studies have shown a positive association between thyroid-stimulating hormone (TSH) and body mass index. Recent studies have shown a significant increase in the prevalence of subclinical hypothyroidism (SCH) in obesity. Weight reduction after Roux-en-Y gastric bypass (RYGB) seems to significantly decrease TSH levels.
The purpose of this study was to evaluate the prevalence of SCH in obese patients (class II and III) and to observe the behavior of thyroid hormones (TSH, hormone triiodothyronine, thyroxine, free thyroxine) with significant weight loss after RYGB.
Hospital Nossa Senhora das Graças, Curitiba, Paraná, Brazil.
We retrospectively reviewed the medical records of 215 obese patients who underwent RYGB between 2005 and 2012 with a follow-up of at least 2 years. The study was observational and descriptive. The selected times for clinical and laboratory evaluations were preoperative, 3, 6, 12, and 24 months after the procedure. Association, correlation, and variance analyses were performed.
The prevalence of SCH preoperatively was 9.3%. SCH was corrected in 89.5% of patients 12 months after RYGB. We did not find an association between TSH and BMI (r = .002, P = .971). There was a positive impact of bariatric surgery on all metabolic variables. We showed that serum TSH level had no positive correlation with the presence or absence of metabolic syndrome.
Weight loss after bariatric surgery leads to normalization of TSH levels in most patients and none developed overt hypothyroidism. Obese patients with SCH should not be treated with thyroid hormone replacement. Serial monitoring of thyroid function after obesity therapy seems to be a reasonable approach.
The effect of bariatric surgery on hypothyroidism: Sleeve gastrectomy versus gastric bypass
2018, Surgery for Obesity and Related Diseases
Citation Excerpt :
This theory is related to changes in the ghrelin level after surgery. It was previously shown that circulating ghrelin levels significantly correlated with TSH levels, among other hormones [18]. There is also evidence that ghrelin levels are suppressed after LRYGB and LSG (however, not after laparoscopic adjustable gastric banding) [19].
Hypothyroidism is prevalent in morbidly obese patients and may improve after a weight reduction surgery.
Laboratory and clinical changes in hypothyroid patients undergoing laparoscopic sleeve gastrectomy (LSG) or laparoscopic Roux-en-Y gastric bypass (LRYGB) were compared and evaluated.
Data were retrieved from a prospectively collected database of 2 public bariatric units.
Patients with hypothyroidism prior to bariatric procedure were evaluated for changes in thyroid stimulating hormone (TSH) and changes or cessation of hormone replacement therapy after surgery. Correlation between changes in TSH levels and percentage of excess weight loss and comparison between effects of LSG and LRYGB were evaluated.
Ninety patients were included. Mean follow-up was 11 ± 9 .73 months. Mean body mass index decreased from 43.8 to 33.2 kg/m². Forty patients had deranged elevated TSH levels prior to surgery that decreased significantly after surgery (mean 6.6 ± 1.9 to 2.9 ± 1.5 mU/L, P < .01). Of patients receiving hormone replacement therapy prior to surgery, 42% required lower doses, with a 61% mean decrease in doses, while 10% stopped hormone replacement therapy completely. No correlation was found between the improvement in TSH and percentage of excess weight loss. A significant advantage to one of the bariatric procedures (LSG [61] and LRYGB [29]) could not be established.
LSG and LRYGB both proved to improve thyroid function in hypothyroid obese patients. No procedure was found to be superior. No correlation was found between percentage of excess weight loss and TSH reduction. This implies that the effect of bariatric surgery on the improvement of thyroid functions is mediated by mechanisms other than weight loss, probably hormonal.
Biochemical properties and biological actions of obestatin and its relevence in type 2 diabetes
2018, Peptides
Citation Excerpt :
Similarly, patients with bulimia nervosa are reported to have raised obestatin levels [149,150], although one study found obestatin levels to be unaltered in this condition [118]. Furthermore, in cases of hypothyroidism (associated with weight gain) obestatin levels were decreased, and conversely in cases of hyperthyroidism (associated with weight loss) levels were increased [152], although another study found obestatin levels to be decreased in hyperthyroidism [153]. Given its apparent vasorelaxant actions, it is may be not surprising that alterations in circulating obestatin have been linked with blood pressure changes.
Obestatin was initially discovered in rat stomach extract, and although it is principally produced in the gastric mucosa, it can be found throughout the gastrointestinal tract. This 23-amino acid C-terminally amidated peptide is derived from preproghrelin and has been ascribed a wide range of metabolic effects relevant to type 2 diabetes. Obestatin reportedly inhibits gastrointestinal motility, reduces food intake and lowers body weight and improves lipid metabolism. Furthermore, it appears to exert actions on the pancreatic β-cell, most notably increasing β-cell mass and upregulating genes associated with insulin production and β-cell regeneration, with relevance to type 2 diabetes. It is becoming evident that obestatin also exerts pleiotropic effects on the cardiovascular system, possibly modulating blood pressure, endothelial function and triggering cardioprotective mechanisms, which may be important in determining cardiovascular outcomes in type 2 diabetes. Furthermore, it seems that like other gut peptides obestatin has neuroprotective properties. This review examines the biochemical properties of the obestatin peptide (its structure, sequence, stability and distribution) and the candidate receptors through which it may act. It provides a balanced examination of the reported pancreatic and extrapancreatic actions of obestatin and evaluates its potential relevance with respect to diabetes therapy, together with discussion of direct evidence linking alterations in obestatin signalling with obesity/diabetes and other diseases.
Thyroid Hormone Homeostasis in Weight Loss and Implications for Bariatric Surgery
2017, Metabolism and Pathophysiology of Bariatric Surgery: Nutrition, Procedures, Outcomes and Adverse Effects
Thyroid hormone (TH) action modulates energy metabolism, as indicated by the dramatic changes in energy expenditure in overt hypo- and hyperthyroidism. While severe hyperthyroidism is associated with dramatic weight loss, hypothyroidism contributes only marginally to weight gain. The thyroid axis is profoundly affected by bariatric surgery–induced weight loss. The reduction in leptin inhibits the secretion of thyrotropin-releasing hormone, while the catabolic state inhibits the peripheral conversion of TH, resulting in a reduction in triiodothyronine (T3) levels. The postsurgical changes in gastrointestinal motility may result in dysregulation in the absorption of exogenous TH therapy, and in the hepatobiliary recirculation of TH. Furthermore, micronutrient deficits caused by bariatric surgery procedures may result in thyroid dysfunction. Finally, new evidence indicates that bariatric surgery procedures may contribute to expansion of brown adipose tissue. Collectively, weight loss and bariatric surgery procedures affect the endogenous thyroid axis and the effectiveness of TH replacement therapy.
Effect of Roux-en-Y gastric bypass on the remission of type 2 diabetes: a 3-year study in Chinese patients with a BMI <30 kg/m<sup>2</sup>
2016, Surgery for Obesity and Related Diseases
Citation Excerpt :
Leptin is produced by adipocytes and was shown to influence the secretion of several hypothalamic hormones, including thyrotropin-releasing hormone [23]. Other studies have suggested that levels of gut hormones such as ghrelin are correlated with thyroid hormone levels [24]. It is possible that one of the pathways that results in the resolution of the metabolic syndrome is by modulating thyroid hormones [25].
Roux-en-Y gastric bypass (RYGB) is an effective treatment for patients with type 2 diabetes (T2D) and morbid obesity. However, T2D remission after surgery has not been adequately studied in Chinese patients with a body mass index (BMI)<30 kg/m².
The objective of this study was to evaluate the 3-year effect of RYGB among patients with T2D with a BMI<30 kg/m² and elucidate the predictors of T2D remission.
Department of General Surgery, Shanghai Jiao Tong University Affiliated Sixth People’s Hospital, Shanghai, China.
Sixty-six Chinese patients with T2D and a BMI 25–30 kg/m² were retrospectively examined for metabolic outcomes 3 years after RYGB. Remission was defined as glycated hemoglobin (HbA1C)<6.5% and no medications. Binary logistic regression analysis was used to identify preoperative parameters independently predictive of diabetes remission at 1 and 3 years postoperatively [variables: sex, age, BMI, T2D duration, plasma glucose 2 hours after meal, HbA1C, fasting C-peptide, visceral fat area, free triiodothyronine, and thyroid-stimulating hormone. There was no significant difference in fasting insulin or glucose between the remission and no remission groups.
Patients were a mean 50.4±11.4 years of age at baseline, and 57.6% were female. Mean T2D duration was 8.9±5.2 years, baseline HbA1C level was 8.3±1.9%, and baseline BMI was 28.2±1.2 kg/m² (range: 25.5–30.0). BMI was 22.5±1.8 kg/m² (range: 19.1–28.0) at 1 year and 23.0±1.76 kg/m² (range: 19.7–28.0) at 3 years. Remission was achieved in 49 patients (74.2%) at 1 year and 38 patients (57.6%) at 3 years. There was a significant reduction in medication for diabetes, hypertension, and hyperlipidemia (P<.01). Compared with patients in the no remission group, patients in the remission group had higher fasting C-peptide levels (P<.01) and free triiodothyronine levels (P = .01) at 1 year. Multiple logistic regression analysis confirmed that fasting C-peptide (odds ratio = 3.795, P = .007) and free triiodothyronine (odds ratio = 4.661, P = .019) levels were predictors of T2D remission at 1 year. No significant difference was found between the 2 groups at 3 years.
RYGB resulted in significant clinical and biochemical improvements in Chinese patients with BMI 25–30 kg/m² and T2D. Appropriate patient selection (better β-cell function) may produce better outcomes.

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View full text

Is association between thyroid hormones and gut peptides, ghrelin and obestatin, able to suggest new regulatory relation between the HPT axis and gut?

Highlights

Abstract

Background

Materials and methods

Results

Conclusion

Introduction

Section snippets

Subjects and study design

Results

Discussion

Conclusion

Acknowledgment

Regul Pept

Mol Cell Endocrinol

Peptides

Peptides

Psychoneuroendocrinology

Cytokine

Am J Med Sci

Ghrelin gene products and the regulation of food intake and gut motility

Pharmacol Rev

A striking example of neuroendocrine peptide pleiotropy

Med Sci (Paris)

Ghrelin is a growth-hormone-releasing acylated peptide from stomach

Nature

The ghrelin/obestatin balance in the physiological and pathological control of growth hormone secretion, body composition and food intake

J Neuroendocrinol

Neuroendocrine body weight regulation: integration between fat tissue, gastrointestinal tract, and the brain

Endokrynol Pol

Gastrointestinal regulatory peptides and their effects on fat tissue

Curr Opin Endocrinol Diabetes Obes

Obestatin, a peptide encoded by the ghrelin gene, opposes ghrelin's effects on food intake

Science

Obestatin induction of early-response gene expression in gastrointestinal and adipose tissues and the mediatory role of G protein-coupled receptor, GPR39

Mol Endocrinol

Circulating obestatin levels and the ghrelin/obestatin ratio in obese women

Eur J Endocrinol

Ghrelin in pathological conditions

Endocr J

Role of surrogate markers of atherosclerosis in clinical and subclinical thyroidism

Int J Endocrinol

Subclinical thyroid disease: scientific review and guidelines for diagnosis and management

JAMA