Fasting Unmasks a Strong Inverse Association between Ghrelin and Cortisol in Serum: Studies in Obese and Normal-Weight Subjects (original) (raw)
Related papers
2010
The gut peptide, ghrelin, may participate in the control of energy homeostasis and pituitary hormone secretion in humans, stimulating both food intake and, at pharmacological doses, ACTH and cortisol secretion. Meal consumption and weight loss regulate ghrelin levels, but less is known about the relationship of ghrelin to body composition, aging, menopausal status, and lipid metabolism. Therefore, 60 adult men and women of widely varying ages and weights were characterized in terms of body composition and levels of ghrelin, glucose, insulin, lipids, and cortisol. Fasting ghrelin levels correlated positively with age and negatively with BMI and fat cell size, but were not related to fat mass, intraabdominal fat, or lean mass. Fasting ghrelin levels correlated most strongly with insulin levels (r ؍ ؊0.39; P ؍ 0.002), insulin resistance as determined by the quantitative insulin sensitivity check index (r ؍ 0.38; P ؍ 0.003), and high-density lipoprotein cholesterol levels (r ؍ 0.33; P ؍ 0.009). Meal-induced ghrelin suppression correlated with the postprandial rise in insulin (r ؍ 0.39; P < 0.05). Ghrelin levels were similar in men and women and did not vary by menopausal status or in association with cortisol levels. Our data are consistent with the hypotheses that insulin may negatively regulate ghrelin and that high-density lipoprotein may be a carrier particle for circulating ghrelin. (J Clin Endocrinol Metab 88: 5747-5752, 2003)
Influence of Cortisol Status on Leptin Secretion
Pituitary, 2001
The discovery of the adipocyte-produced hormone leptin has changed the field of obesity research and our understanding of energy homeostasis. It is now accepted that leptin is the afferent loop informing the hypothalamus about the states of fat stores, with hypothalamic efferents regulating appetite and energy expenditure. I addition, leptin has a role as a metabolic adaptator in overweight and fasting states. New and previously unsuspected neuroendocrine roles have emerged for leptin. Leptin participates in the expression of CRH in the hypothalamus, interacts at the adrenal level with ACTH, and is regulated by glucocorticoids. Since leptin and cortisol show an inverse circadian rhythm, it has suggested that a regulatory feedback is present. However glucocorticoids appears to play a modulatory, but not essential roles in generating leptin diurnal rhythm. Glucocortiocids act directly on the adipose tissue and increase leptin syntesis and secretion in humans. Leptin levels are markedly increased in Cushing's syndrome patients and in others pseudo-Cushing's syndrome states. Glucocorticoids appears to act as a key modulator of body weight and food intake, promoting leptin secretion by adipocytes, limiting central leptin induced effects and favoring those of the NPY. Furthermore the modulatory role of glucocorticoids could be altered in obesity, but the precise mode of action remains to be established. The relevance of this finding merits further studies.
Circadian rhythm of acylated ghrelin, leptin, growth hormone, IGF-1, IGFBP-1 and IGFBP-3
International Journal of Endocrinology & Metabolism, 2011
Disturbance of anabolic hormones such as ghrelin and leptin could be the cause of developing cardiovascular diseases. In addition, imbalance between ghrelin/GH/IGF-1 axis and leptin may be the reason for reduction of ejection fraction among cardiovascular patients. Background: Following detection of receptors for ghrelin and growth hormone (GH) in the cardiovascular system, different clinical trials have used ghrelin or GH for the treatment of cardiac patients. While some of these trials reported improvements in the patients' situation, others reported deterioration. Objectives: To clarify the contradictory outcomes, we designed this study to evaluate the circadian rhythms of acylated ghrelin, GH, and the related factors [Insulin-like Growth Factor-1 (IGF-1), Insulin-like Growth Factor Binding Proteins 1 and 3 (IGFBP-1 and IGFBP-3)], and leptin in patients with reduced ejection fraction (rEF). Patients and Methods: Ten patients with rEF and an equal number of healthy control subjects matched for age and gender participated in this study according to inclusion criteria. All participants were hospitalized in the cardiac care unit (CCU), under identical conditions during collection of blood (every 2 hours). Primary processing of samples was carried out immediately and the plasma was stored at-20ºC until evaluation of the aforementioned parameters using ELISA methods. Results: Evaluation of the collected data showed that among aged participants only circulating leptin is gender-dependent, while the patients had significantly (P < 0.001) lower ghrelin, GH, IGF-1, and IGFBP-1, but a higher level of IGFBP-3 compared to the control group. In addition, except for GH that showed a mild circadian rhythm, the parameters we examined did not have a significant circadian rhythm. Correlation analysis of the data showed a positive correlation between ghrelin and GH or IGF-1, and significant negative or positive correlations between leptin and IGFBP-1, or IGFBP-3, respectively, in both groups. Conclusions: Here, for the first time, we show that circulating ghrelin, GH, and IGF-1 levels are reduced in the patients with rEF, and the condition of patients is deteriorated not only due to reduced IGF-1 but also due to reduction of IGFBP-1 or increase of IGFBP-3, which may be influenced by circulating leptin. Finally, disturbance of the balance between ghrelin/GH/IGF-1 and leptin may be the cause of rEF, and thus evaluation of these parameters could provide diagnostic as well as prognostic tools for the treatment of these patients.
Morning cortisol is lower in obese individuals with normal glucose tolerance
Diabetes, Metabolic Syndrome and Obesity: Targets and Therapy, 2011
There is no consensus on the role of cortisol in the pathogenesis of obesity and metabolic syndrome (MS). This cross-sectional study aimed to analyze the relationship of morning plasma cortisol and adrenocorticotropic hormone (ACTH) levels with body mass index (BMI) and glucose tolerance. Subjects and methods: The sample frame was the "Offspring of individuals with diabetes study" database. A total of 358 offspring of individuals with type 2 diabetes mellitus (T2DM) and 287 individuals without a known family history of T2DM were recruited for the study. Subjects who were $10 years of age were selected from the database for analysis. Subjects with T2DM were excluded. All participants underwent a 75 g oral glucose tolerance test (OGTT), and blood samples were collected at 0, 30, 60, and 120 minutes for glucose, insulin and C-peptide. Plasma cortisol, ACTH, and lipid profile were estimated from the fasting sample.
Journal of Clinical …, 2004
Ghrelin, a stomach-derived orexigenic peptide, and leptin, a fat-derived anorexigenic hormone, act primarily in the hypothalamus to regulate energy homeostasis and have been reported to be regulated in opposite directions by acute and chronic changes in nutritional state. Nutritional, anthropometric, and hormonal predictors of circulating ghrelin have not yet been fully elucidated, and whether ghrelin is regulated by leptin in humans remains unknown. To address these questions, we performed cross-sectional and interventional studies. In 120 healthy men and women, ghrelin was negatively associated with leptin as well as overall and central adiposity, but not with total energy or specific macronutrient intake. The sexual dimorphism in ghrelin levels (higher levels in women than in men) and the negative correlation between ghrelin and insulin are largely mediated by central adiposity. In six lean men, complete fasting for 3 d resulted in a low leptin state without a major change in fat mass and abolished the meal-related secretory pattern of ghrelin without increasing 24-h ghrelin levels. In addition, recombinant human leptin administration in physiological and pharmacological doses did not regulate ghrelin over several hours to a few days. These data do not support a role for regulation of circulating ghrelin by leptin levels independently of changes in adiposity and suggest that the leptin and ghrelin systems for energy homeostasis function independently of each other in healthy humans. (J Clin Endocrinol Metab 89: 335-343, 2004) Abbreviations: AUC, Area under the curve; BIA, bioelectrical impedance analysis; BMI, body mass index; CV, coefficient of variation; DEXA, dual energy x-ray absorptiometry; %FM, percent fat mass; r-metHuLeptin, recombinant methionyl human leptin; WC, waist circumference; WHR, waist to hip ratio. JCEM is published monthly by The Endocrine Society (http://www. endo-society.org), the foremost professional society serving the endocrine community.
Endogenous Circulating Ghrelin Does Not Mediate Growth Hormone Rhythmicity or Response to Fasting
The Journal of Clinical Endocrinology & Metabolism, 2005
GH secretory profiles in humans are pulsatile and exhibit nocturnal elevation during the early hours of sleep. Fasting augments GH output and rhythmicity. Ghrelin was suggested to exhibit nocturnal increases and to rise in response to nutritional deprivation. We examined whether ghrelin may be an underlying mechanism of GH rhythmicity and response to fasting. We studied nine young healthy subjects during normal feeding and after 2 d of complete fasting. Plasma GH was measured every 10 min, and plasma total and active ghrelins were measured every 20 min. Fasting augmented mean daily plasma GH (1.47 ؎ 0.25 vs. 3.30 ؎ 0.6 g/liter; P ؍ 0.012). Neither mean daily total ghrelin (4.19 ؎ 0.64 vs. 4.35 ؎ 0.74 g/liter; P ؍ 0.75) nor mean daily active ghrelin (0.13 ؎ 0.02 vs. 0.13 ؎ 0.02 g/liter; P ؍ 0.34) changed as a result of fasting. All subjects exhibited nocturnal augmentation of GH secretion; there were no corresponding nocturnal increases in either total or active ghrelin concentrations. Similarly, cross-correlation analysis failed to find any relation between GH and ghrelin pulses. We conclude that ghrelin is unlikely to be of importance in the generation of rhythmic or nutritionally mediated GH secretion. (J Clin Endocrinol Metab 90: 2982-2987, 2005)
Clinical Endocrinology, 2005
Objective Glucagon secretion is stimulated by fasting and inhibited postprandially, a pattern that mimics the secretory profiles of both ghrelin and GH. We thus hypothesized that glucagon may be a determinant of the changes in circulating ghrelin and GH that occur in relation to meals. The objective of the study was to explore this hypothesis by determining the ghrelin and GH response to a bolus of glucagon or saline in healthy subjects. Subjects and measurements Nine healthy volunteers, mean age 47 years (range 33 -58) and body mass index (BMI) 24 kg / m 2 (range 20·9-27·6) were recruited and received either 1 mg glucagon ( n = 9) or 1 ml saline ( n = 6) subcutaneously on separate days between 0800 and 0830 h after an overnight fast. Venous blood was then sampled at 15-min intervals during the first hour, followed by 30-min intervals up to 4 h for glucose, insulin, GH, cortisol, somatostatin and ghrelin. Results Mean ± SE basal ghrelin was 213·1 ± 34·3 pmol / l and decreased significantly by 15 min after glucagon administration to 179·3 ± 28 pmol / l ( P = 0·01), then remaining suppressed relative to the basal value until 240 min after glucagon. Plasma insulin increased from a basal value of 46·7 ± 7·7 pmol/l to a peak of 327·1 ± 54·9 pmol / l ( P < 0·0001). There was an inverse statistical relationship between the increase in insulin over the first 120 min and the decrease in ghrelin ( P = 0·005), while somatostatin, GH and glucose were not significant contributors to the decrease in ghrelin ( P > 0·05). Mean ± SE basal GH was 7·3 ± 2·9 µ g/l and increased by 150 min after glucagon to a peak of 20·5 ± 6·8 µ g /l ( P = 0·006). Changes in neither ghrelin nor glucose were related to the increase in GH ( P = 0·7). Saline administration did not produce any significant change in ghrelin, insulin or somatostatin although the expected diurnal reduction in cortisol ( P < 0·05) was observed. Conclusions Our study found no evidence that glucagon stimulates ghrelin secretion in humans and supports the hypothesis that insulin is a negative regulator of ghrelin secretion in the postprandial state. We did not find a negative relationship between endogenous somatostatin and ghrelin despite earlier reports that exogenously administered somatostatin analogues suppress plasma ghrelin. Finally, glucagon-induced GH secretion is not mediated by an increase in plasma ghrelin.
Differential Responses of Circulating Ghrelin to High-Fat or High-Carbohydrate Meal in Healthy Women
The Journal of Clinical Endocrinology & Metabolism, 2003
The effects of specific nutritional factors on ghrelin secretion have not been investigated in humans. Therefore, we assessed ghrelin responses to a high-carbohydrate meal (1217 kcal with 77% carbohydrates, 10% protein, and 13% lipids) and to an isocaloric high-fat meal (15% carbohydrates, 10% proteins, and 75% lipids) in 14 nonobese healthy women. Eleven subjects also rated their hunger feelings on visual analog scales. Circulating ghrelin abruptly fell after both meals, but, after the carbohydrate meal, its maximum percent decrease was significantly greater than after the fat meal (P ؍ 0.02). Plasma insulin and glucose levels rose after the meals, but their in-creases were significantly higher after the carbohydrate meal than after the fat meal. No significant change was observed in circulating leptin after both meals. Moreover, compared with the fat meal, the carbohydrate meal had a significantly greater suppressant effect on hunger feelings. Plasma ghrelin changes were significantly associated with hunger changes (P < 0.007). These findings show that circulating ghrelin is differently suppressed by diet manipulations. The mechanisms responsible for such a phenomenon and its possible implication in the physiology of human satiety remain to be elucidated. (J Clin Endocrinol Metab 88: 5510 -5514, 2003)