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Alvarez-Crespo M, Gil-Lozano M, Diz-Chaves Y, González-Matias LC, Mallo F. Elevation of ghrelin by B-adrenergic activation is independent of glucose variations and feeding regimen in the rat. Endocrine 2025; 88:434-445. [PMID: 40169505 PMCID: PMC12069131 DOI: 10.1007/s12020-024-04156-w] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 10/15/2024] [Accepted: 12/28/2024] [Indexed: 04/03/2025]
Abstract
Ghrelin is a signal involved in the initiation of meals in rodents and humans. Circulating ghrelin levels are elevated before mealwes and reduced after food intake. Several factors have been identified as effective modulators of ghrelin levels. Vagal activation reduced ghrelin in rats, as well as oral carbohydrate and lipid administration in rats and humans. Some hormones, such as incretins, also reduce ghrelin: GLP-1 reduced ghrelin in humans, and Ex4, a GLP-1 receptor agonist, potently inhibited ghrelin in rodents. On the other hand, fasting promotes increases in ghrelin that anticipate the start of meals. We report that beta-adrenergic activation with isoproterenol promotes large acute elevations of circulating ghrelin levels, both in anesthetized and conscious freely-moving rats, either on "ad libitum" feeding or on a fasting regimen.These effects are dose-dependent, caused by intravenous, intraperitoneal, and oral administration, and independent of variations in glucose levels. Pharmacological modulation of β1 and β2 adrenergic receptors with specific agonists and antagonists showed that ghrelin increases are stimulated by β1-adrenergic activation, but also partially by β2-adrenergic activation, suggesting that activation of both is necessary to elicit complete ghrelin elevations. Meanwhile, glucose increases dependent on adrenergic activation appear to be mediated only by β2-adrenergic receptors. In addition, the effects of isoproterenol on increasing ghrelin levels are potent enough to overcome the marked inhibition exerted by exendin-4 that we have previously demonstrated. We also found that administration of isoproterenol in drinking water increases basal ghrelin levels and simultaneous food intake in animals eating ad libitum. Beta-adrenergic activation promotes increases in ghrelin levels in vivo prior to food intake, both in rats eating ad libitum and in fasting rats that already have elevated ghrelin levels, in a time- and dose-dependent manner. In addition, the effects of isoproterenol on increasing ghrelin levels are potent enough to overcome the marked inhibition exerted by exendin-4 that we have previously demonstrated. We also found that administration of isoproterenol in drinking water increases basal ghrelin levels and simultaneous food intake in animals eating ad libitum. Beta-adrenergic activation promotes increases in ghrelin levels in vivo prior to food intake, both in eating ad libitum and in fasting rats that already have elevated ghrelin levels, in a time- and dose-dependent manner.
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Affiliation(s)
- Mayte Alvarez-Crespo
- LabEndoTeam - Laboratory of Endocrinology - Department of Functional Biology and Health Sciences - University of Vigo - Campus as Lagoas - Marcosende, Vigo, Spain
| | - Manuel Gil-Lozano
- LabEndoTeam - Laboratory of Endocrinology - Department of Functional Biology and Health Sciences - University of Vigo - Campus as Lagoas - Marcosende, Vigo, Spain
| | - Yolanda Diz-Chaves
- LabEndoTeam - Laboratory of Endocrinology - Department of Functional Biology and Health Sciences - University of Vigo - Campus as Lagoas - Marcosende, Vigo, Spain
| | - Lucas Carmelo González-Matias
- LabEndoTeam - Laboratory of Endocrinology - Department of Functional Biology and Health Sciences - University of Vigo - Campus as Lagoas - Marcosende, Vigo, Spain
- Galicia Sur Health Research Institute (IIS Galicia Sur). SERGAS-UVIGO, Vigo, Spain
| | - Federico Mallo
- LabEndoTeam - Laboratory of Endocrinology - Department of Functional Biology and Health Sciences - University of Vigo - Campus as Lagoas - Marcosende, Vigo, Spain.
- Galicia Sur Health Research Institute (IIS Galicia Sur). SERGAS-UVIGO, Vigo, Spain.
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Holliday A, Horner K, Johnson KO, Dagbasi A, Crabtree DR. Appetite-related Gut Hormone Responses to Feeding Across the Life Course. J Endocr Soc 2025; 9:bvae223. [PMID: 39777204 PMCID: PMC11702868 DOI: 10.1210/jendso/bvae223] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 08/16/2024] [Indexed: 01/11/2025] Open
Abstract
Appetite-related hormones are secreted from the gut, signaling the presence of nutrients. Such signaling allows for cross-talk between the gut and the appetite-control regions of the brain, influencing appetite and food intake. As nutritional requirements change throughout the life course, it is perhaps unsurprising that appetite and eating behavior are not constant. Changes in appetite-related gut hormones may underpin these alterations in appetite and eating. In this article, we review evidence of how the release of appetite-related gut hormones changes throughout the life course and how this impacts appetite and eating behaviour. We focus on hormones for which there is the strongest evidence of impact on appetite, food intake, and body weight: the anorexigenic glucagon like peptide-1, peptide tyrosine tyrosine, and cholecystokinin, and the orexigenic ghrelin. We consider hormone concentrations, particularly in response to feeding, from the very early days of life, through childhood and adolescence, where responses may reflect energy requirements to support growth and development. We discuss the period of adulthood and midlife, with a particular focus on sex differences and the effect of menstruation, pregnancy, and menopause, as well as the potential influence of appetite-related gut hormones on body composition and weight status. We then discuss recent advancements in our understanding of how unfavorable changes in appetite-related gut hormone responses to feeding in later life may contribute to undernutrition and a detrimental aging trajectory. Finally, we briefly highlight priorities for future research.
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Affiliation(s)
- Adrian Holliday
- School of Biomedical, Nutritional, and Sport Sciences, Faculty of Medical Sciences, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
- Human Nutrition and Exercise Research Centre, Population Health Sciences Institute, Newcastle University, Newcastle Upon Tyne NE2 4HH, UK
| | - Katy Horner
- Institute of Sport and Health, University College Dublin, Belfield, Dublin D04 V1W8, Ireland
| | - Kelsie O Johnson
- Research Institute for Sport and Exercise Sciences, Liverpool John Moores University, Liverpool L3 5RF, UK
| | - Aygul Dagbasi
- Section of Nutrition, Department of Metabolism Digestion and Reproduction, Imperial College London, Hammersmith Campus, London W12 0NN, UK
| | - Daniel R Crabtree
- The Rowett Institute, School of Medicine, Medical Sciences and Nutrition, University of Aberdeen, Aberdeen AB25 2ZD, UK
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Ozmen F, Şahin TT, Dolgun A, Ozmen MM. Changes in serum ghrelin and resistin levels after sleeve gastrectomy versus one anastomosis gastric bypass: prospective cohort study. Int J Surg 2024; 110:5434-5443. [PMID: 38833355 PMCID: PMC11392113 DOI: 10.1097/js9.0000000000001608] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/05/2024] [Accepted: 04/29/2024] [Indexed: 06/06/2024]
Abstract
INTRODUCTION Humoral factors and neural mechanisms play a central role in the pathogenesis of obesity and in weight loss following bariatric surgery. Although various hormones and adipokines, including ghrelin and resistin, are linked to obesity, studies analyzing the changes in fasting ghrelin and resistin levels in patients following one anastomosis gastric bypass (OAGB) are lacking. AIM The authors aimed to investigate resistin and ghrelin levels before and after two commonly used bariatric procedures with different mechanisms of action: sleeve gastrectomy (SG) and OAGB. PATIENTS AND METHODS Fasting serum ghrelin and resistin levels were evaluated by using ELISA in a nonrandomized, prospective cohort study for the pattern of changes in the preoperative period and 1 week, 1 month, 3 months and, 12 months after surgery in age and sex-matched patients with BMI ≥40 kg/m 2 undergoing either SG ( n =40) or OAGB ( n =40). Their relationships with demographic parameters such as body weight, BMI, presence of T2DM, HbA 1 C, and Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) index were also evaluated. RESULTS OAGB was superior in weight control compared to the SG group. There were significant differences in resistin and ghrelin levels between the OAGB and SG groups. Ghrelin decreased more in the SG group than the preoperative values. This change in ghrelin levels was more significant at 1 year after SG [preoperative mean (range) level of 334.2 (36.6-972.1) pg/ml decreased to 84 (9.1-227) pg/ml at 1 year] whereas in the OAGB group no significant change was observed [preoperative mean (range) level of 310 (146-548) pg/ml decreased to 264 (112-418) pg/ml at 1 year]. Resistin levels decreased in both groups, especially after 3 months and onward following both operations [the mean (range) resistin levels were 2.6 (0.87-5.4) ng/ml and decreased to 1.1 (0.5-2.4) ng/ml in the SG group vs 2.48 (0.89-6.43) ng/ml decreased to 0.72 (0.35-1.8) ng/ml in OAGB group at 1 year], which was in parallel with changes in HOMA-IR index, body weight, and BMI changes at 1st year. HOMA-IR index changes were similar, but more prominent after OAGB. OAGB was als3 three months and onward), and HOMA-IR changes. CONCLUSION This is the first study to compare fasting ghrelin and resistin levels after OAGB and SG. Although similar changes were observed, ghrelin changes were more prominent after SG, whereas resistin were observed after OAGB. OAGB was superior in T2DM control, which was in parallel with weight loss, fasting resistin levels, and HOMA-IR changes suggesting a possible effect of resistin after OAGB in glucose metabolism and insulin resistance.
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Affiliation(s)
- Fusun Ozmen
- Department of Basic Oncology, Cancer Institute, Hacettepe University
| | - Tevfik T. Şahin
- Depatment of Surgery, Medical School, Hacettepe University
- Liver Transplant Institute, Inonu University, Malatya
| | - Anil Dolgun
- Department of Biostatistics, Medical School, Hacettepe University, Ankara
| | - M. Mahir Ozmen
- Depatment of Surgery, Medical School, Hacettepe University
- Department of Surgery, Faculty of Medicine, Bahcesehir University (BAU), Istanbul, Turkey
- Department of Surgery, Faculty of Medicine, University of La Sapienza, Rome, Italy
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Abdalla MMI. Insulin resistance as the molecular link between diabetes and Alzheimer's disease. World J Diabetes 2024; 15:1430-1447. [PMID: 39099819 PMCID: PMC11292327 DOI: 10.4239/wjd.v15.i7.1430] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/14/2024] [Revised: 04/08/2024] [Accepted: 05/06/2024] [Indexed: 07/08/2024] Open
Abstract
Diabetes mellitus (DM) and Alzheimer's disease (AD) are two major health concerns that have seen a rising prevalence worldwide. Recent studies have indicated a possible link between DM and an increased risk of developing AD. Insulin, while primarily known for its role in regulating blood sugar, also plays a vital role in protecting brain functions. Insulin resistance (IR), especially prevalent in type 2 diabetes, is believed to play a significant role in AD's development. When insulin signalling becomes dysfunctional, it can negatively affect various brain functions, making individuals more susceptible to AD's defining features, such as the buildup of beta-amyloid plaques and tau protein tangles. Emerging research suggests that addressing insulin-related issues might help reduce or even reverse the brain changes linked to AD. This review aims to explore the rela-tionship between DM and AD, with a focus on the role of IR. It also explores the molecular mechanisms by which IR might lead to brain changes and assesses current treatments that target IR. Understanding IR's role in the connection between DM and AD offers new possibilities for treatments and highlights the importance of continued research in this interdisciplinary field.
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Affiliation(s)
- Mona Mohamed Ibrahim Abdalla
- Department of Human Biology, School of Medicine, International Medical University, Bukit Jalil 57000, Kuala Lumpur, Malaysia
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Lopes KG, da Silva VL, de Azevedo Marques Lopes F, Bouskela E, Coelho de Souza MDG, Kraemer-Aguiar LG. Ghrelin and glucagon-like peptide-1 according to body adiposity and glucose homeostasis. ARCHIVES OF ENDOCRINOLOGY AND METABOLISM 2023; 67:e000611. [PMID: 37252699 PMCID: PMC10665067 DOI: 10.20945/2359-3997000000611] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Subscribe] [Scholar Register] [Received: 07/23/2022] [Accepted: 11/17/2022] [Indexed: 05/31/2023]
Abstract
Objective We investigated the biological behavior of ghrelin and glucagon-like peptide-1 (GLP-1) after a standard liquid meal according to body adiposity and glucose homeostasis. Subjects and methods This cross-sectional study included 41 individuals (92.7% women; aged 38.3 ± 7.8 years; BMI 32.2 ± 5.5 kg/m2) allocated into three groups according to body adiposity and glucose homeostasis, as follows: normoglycemic eutrophic controls (CON, n = 11), normoglycemic with obesity (NOB, n = 15), and dysglycemic with obesity (DOB, n = 15). They were tested at fasting and 30 and 60 min after the ingestion of a standard liquid meal in which we measured active ghrelin, active GLP-1, insulin, and plasma glucose levels. Results As expected, DOB exhibited the worst metabolic status (glucose, insulin, HOMA-IR, HbA1c) and an inflammatory status (TNF-α) at fasting, besides a more significant increase in glucose than postprandial NOB (p ≤ 0.05). At fasting, no differences between groups were detected in lipid profile, ghrelin, and GLP-1 (p ≥ 0.06). After the standard meal, all groups exhibited a reduction in ghrelin levels between fasting vs. 60 min (p ≤ 0.02). Additionally, we noticed that GLP-1 and insulin increased equally in all groups after the standard meal (fasting vs. 30 and 60 min). Although glucose levels increased in all groups after meal intake, these changes were significantly more significant in DOB vs. CON and NOB at 30 and 60 min post-meal (p ≤ 0.05). Conclusion Time course of ghrelin and GLP-1 levels during the postprandial period was not influenced by body adiposity or glucose homeostasis. Similar behaviors occurred in controls and patients with obesity, independently of glucose homeostasis.
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Affiliation(s)
- Karynne Grutter Lopes
- Unidade de Obesidade, Centro de Pesquisas Clínicas Multiusuário (CePeM), Hospital Universitário Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Programa de Pós-graduação em Fisiopatologia Clínica e Experimental (Fisclinex), Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular (BioVasc), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Vicente Lopes da Silva
- Programa de Pós-graduação em Fisiopatologia Clínica e Experimental (Fisclinex), Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Fernanda de Azevedo Marques Lopes
- Programa de Pós-graduação em Fisiopatologia Clínica e Experimental (Fisclinex), Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Eliete Bouskela
- Unidade de Obesidade, Centro de Pesquisas Clínicas Multiusuário (CePeM), Hospital Universitário Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Programa de Pós-graduação em Fisiopatologia Clínica e Experimental (Fisclinex), Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular (BioVasc), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Maria das Graças Coelho de Souza
- Unidade de Obesidade, Centro de Pesquisas Clínicas Multiusuário (CePeM), Hospital Universitário Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Programa de Pós-graduação em Fisiopatologia Clínica e Experimental (Fisclinex), Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular (BioVasc), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
| | - Luiz Guilherme Kraemer-Aguiar
- Unidade de Obesidade, Centro de Pesquisas Clínicas Multiusuário (CePeM), Hospital Universitário Pedro Ernesto (HUPE), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Programa de Pós-graduação em Fisiopatologia Clínica e Experimental (Fisclinex), Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Laboratório de Pesquisa Clínica e Experimental em Biologia Vascular (BioVasc), Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil
- Endocrinologia, Departamento de Medicina Interna, Faculdade de Ciências Médicas, Universidade do Estado do Rio de Janeiro, Rio de Janeiro, RJ, Brasil,
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Battillo DJ, Malin SK. Relation of Aortic Waveforms with Gut Hormones following Continuous and Interval Exercise among Older Adults with Prediabetes. Metabolites 2023; 13:137. [PMID: 36837756 PMCID: PMC9967213 DOI: 10.3390/metabo13020137] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Grants] [Track Full Text] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/09/2022] [Accepted: 01/13/2023] [Indexed: 01/19/2023] Open
Abstract
Prediabetes raises cardiovascular disease risk, in part through elevated aortic waveforms. While insulin is a vasodilatory hormone, the gut hormone relation to aortic waveforms is less clear. We hypothesized that exercise, independent of intensity, would favor aortic waveforms in relation to gut hormones. Older adults (61.3 ± 1.5 yr; 33.2 ± 1.1 kg/m2) with prediabetes (ADA criteria) were randomized to undertake 60 min of work-matched continuous (CONT, n = 14) or interval (INT, n = 14) exercise for 2 wks. During a 180 min 75-g OGTT, a number of aortic waveforms (applanation tonometry) were assessed: the augmentation pressure (AP) and index (AIx75), brachial (bBP) and central blood pressure (cBP), pulse pressure (bPP and cPP), pulse pressure amplification (PPA), and forward (Pf) and backward pressure (Pb) waveforms. Acylated-ghrelin (AG), des-acylated ghrelin (dAG), GIP, and GLP-1active were measured, and correlations were co-varied for insulin. Independent of intensity, exercise increased VO2peak (p = 0.01) and PPA120min (p = 0.01) and reduced weight (p < 0.01), as well as AP120min (p = 0.02) and AIx75120min (p < 0.01). CONT lowered bSBP (p < 0.02) and bDBP (p < 0.02) tAUC180min more than INT. There were decreases dAG0min related to Pb120min (r = 0.47, p = 0.03), cPP120min (r = 0.48, p = 0.02), and AP120min (r = 0.46, p = 0.02). Declines in AG tAUC60min correlated with lower Pb120min (r = 0.47, p = 0.03) and cPP120min (r = 0.49, p = 0.02) were also found. GLP-1active 0min was reduced associated with lowered AP180min (r = 0.49, p = 0.02). Thus, while CONT exercise favored blood pressure, both intensities of exercise improved aortic waveforms in relation to gut hormones after controlling for insulin.
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Affiliation(s)
- Daniel J. Battillo
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ 08901, USA
| | - Steven K. Malin
- Department of Kinesiology and Health, Rutgers University, New Brunswick, NJ 08901, USA
- Department of Kinesiology, University of Virginia, Charlottesville, VA 22903, USA
- Division of Endocrinology, Metabolism & Nutrition, Rutgers University, New Brunswick, NJ 08901, USA
- New Jersey Institute for Food, Nutrition and Health, Rutgers University, New Brunswick, NJ 08901, USA
- Institute of Translational Medicine and Science, Rutgers University, New Brunswick, NJ 08901, USA
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Interactions of dietary insulin index and dietary insulin load with brain-derived neurotrophic factor (BDNF) Val66Met polymorphism in relation to cardiometabolic markers in Iranian diabetic patients: a cross-sectional study. Br J Nutr 2022; 128:785-792. [PMID: 34605382 DOI: 10.1017/s0007114521003974] [Citation(s) in RCA: 4] [Impact Index Per Article: 1.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/24/2022]
Abstract
The progression of cardiometabolic diseases is determined by both genetic and environmental factors. Gene-diet interactions may therefore be important in modulating the risks of developing metabolic diseases. The objectives were to investigate the effect of the interaction between brain-derived neurotrophic factor (BDNF) Val66Met polymorphisms and dietary insulin index (DII) and dietary insulin load (DIL) on cardiometabolic markers among diabetic patients. In this cross-sectional study, blood samples were collected from 667 patients. DIL and DII were defined using a validated FFQ. Genotyping the BDNF Val66Met polymorphism was conducted by the PCR-Restriction fragment length polymorphism (RFLP) method. Interactions between dietary indices and gene variants were evaluated using a generalised linear model. PGF2a concentrations were significantly higher among Val homozygotes than Met-allele carrier. This study revealed that, compared with individuals with the Val/Val genotype, those with the Met/Val or Met/Met genotype had lower BMI (Pinteraction = 0·04), TAG (Pinteraction = 0·04), leptin (Pinteraction = 0·01), LDL (Pinteraction = 0·04) and total cholesterol (Pinteraction = 0·01) when they consumed diets higher on the DIL index. Moreover, the highest quartile of the DIL, compared with the lowest, showed increase in waist circumference (Pinteraction = 0·02) and LDL/HDL (Pinteraction = 0·04) for Val/Val homozygotes compared with Met-allele carriers. BDNF Val66Met variants may interact with DIL and DII, thus be involved in the development of cardiometabolic risk factors. If diabetic patients with Met alleles regulate dietary intakes, they have a protective opportunity to regulate their cardiometabolic markers.
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Rademacher J, Raddatz D, Ellrott T. Influence of food images with different macronutrient compositions on serum ghrelin levels: Analysis in healthy males. Obes Sci Pract 2022; 8:328-337. [PMID: 35664245 PMCID: PMC9159557 DOI: 10.1002/osp4.577] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2021] [Revised: 11/16/2021] [Accepted: 11/21/2021] [Indexed: 12/02/2022] Open
Abstract
Objective Serum concentrations of the orexigenic hormone ghrelin fluctuate in anticipation of food intake. Moreover, presentation of food images causes an increase in serum ghrelin levels. Thus, the visual system may have a quantifiable role in the development of hunger via the endocrine system. The influence of macronutrient visualization on ghrelin has not yet been investigated. Methods In four separate sessions, ghrelin concentrations, insulin, and glucose levels were compared before and after the presentation of different pictures to 14 male participants. Pictures included neutral, non‐food‐related items or isocaloric dishes whose macronutrient composition corresponded predominately to protein/fat, simple carbohydrates, or complex carbohydrates. Results While pre/post ghrelin concentrations numerically increased in all sessions, significant increases were only observed following neutral and protein/fat pictures. The differences were not significant between food groups and compared to neutral images. Insulin levels decreased in all groups, but no significant differences were observed between sessions. The glucose concentrations were within the euglycemic range. Conclusion The results did not reproduce the induction of ghrelin secretion in different food images. Therefore, it is unclear whether the visual perception of food influences ghrelin secretion or whether separation into macronutrients changes the hormone response. Further research is required to differentiate the interactions of sensory‐specific satiety.
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Affiliation(s)
- Jan‐Gerd Rademacher
- Department of Nephrology and Rheumatology University Medical Center Göttingen Göttingen Germany
| | - Dirk Raddatz
- Department of Gastroenterology, Gastrointestinal Oncology and Endocrinology University Medical Center Göttingen Göttingen Germany
| | - Thomas Ellrott
- Institute for Nutrition and Psychology University Medical Center Göttingen Göttingen Germany
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Qian Y, Xia F, Zuo Y, Zhong M, Yang L, Jiang Y, Zou C. Do patients with Prader-Willi syndrome have favorable glucose metabolism? Orphanet J Rare Dis 2022; 17:187. [PMID: 35525976 PMCID: PMC9077846 DOI: 10.1186/s13023-022-02344-3] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/08/2022] [Accepted: 04/26/2022] [Indexed: 11/26/2022] Open
Abstract
Background In recent years, more studies have observed that patients with Prader–Willi syndrome have lower insulin levels and lower insulin resistance than body mass index-matched controls, which may suggest protected glucose metabolism. Method The PubMed and Web of Science online databases were searched to identify relevant studies published in the English language using the terms “Prader–Willi syndrome” with “glucose”, “insulin”, “diabetes mellitus”, “fat”, “adipo*”, “ghrelin”, “oxytocin”, “irisin” or “autonomic nervous system”. Results The prevalence of impaired glucose intolerance, type 2 diabetes mellitus and some other obesity-associated complications in patients with Prader–Willi syndrome tends to be lower when compared to that in general obesity, which is consistent with the hypothetically protected glucose metabolism. Factors including adipose tissue, adiponectin, ghrelin, oxytocin, irisin, growth hormone and the autonomic nervous system possibly modulate insulin sensitivity in patients with Prader–Willi syndrome. Conclusion Although lower insulin levels, lower IR and protected glucose metabolism are widely reported in PWS patients, the causes are still mysterious. Based on existing knowledge, we cannot determine which factor is of utmost importance and what are the underlying mechanisms, and further research is in urgent need.
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Affiliation(s)
- Yanjie Qian
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Fangling Xia
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Yiming Zuo
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Mianling Zhong
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Lili Yang
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China
| | - Yonghui Jiang
- Department of Genetics, Yale University School of Medicine, New Haven, USA
| | - Chaochun Zou
- Department of Endocrinology, The Children's Hospital of Zhejiang University School of Medicine, National Clinical Research Center for Child Health, No 3333 Binsheng Road, Hangzhou, 310051, China.
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Vasto S, Amato A, Proia P, Baldassano S. Is the Secret in the Gut? SuperJump Activity Improves Bone Remodeling and Glucose Homeostasis by GLP-1 and GIP Peptides in Eumenorrheic Women. BIOLOGY 2022; 11:296. [PMID: 35205162 PMCID: PMC8869418 DOI: 10.3390/biology11020296] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 11/29/2021] [Revised: 02/08/2022] [Accepted: 02/09/2022] [Indexed: 02/01/2023]
Abstract
We showed that twenty weeks of SuperJump activity, an innovative workout training performed on an elastic minitrampoline, reduced bone resorption and increased bone formation in eumenorrheic women acting on the key points of the regulation of bone metabolism. The present study analyzed whether the gastrointestinal hormones are involved in the mechanism of action and if it has an impact on glucose homeostasis. The control group was composed of twelve women, similar to the exercise group that performed SuperJump activity for twenty weeks. The analysis was performed on blood samples and investigated GLP-1, GIP, GLP-2, PYY, ghrelin, glucose, insulin, insulin resistance, β-cell function, and insulin sensitivity. The results showed that the activity contributes to raising the GLP-1and GIP levels, and not on GLP-2, PYY, and ghrelin, which did not change. Moreover, SuperJump activity significantly reduced fasting insulin, glucose, insulin resistance, and increased insulin sensitivity but did not affect beta cell function. These data suggest that GLP-1, and GIP are involved in the mechanism of action that improves bone and glucose homeostasis following 20 weeks of SuperJump activity in eumenorrheic women.
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Affiliation(s)
- Sonya Vasto
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy;
| | - Alessandra Amato
- Sport and Exercise Sciences Research Unit, Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, 90128 Palermo, Italy;
| | - Patrizia Proia
- Sport and Exercise Sciences Research Unit, Department of Psychological, Pedagogical and Educational Sciences, University of Palermo, 90128 Palermo, Italy;
| | - Sara Baldassano
- Department of Biological, Chemical and Pharmaceutical Sciences and Technologies (STEBICEF), University of Palermo, Viale delle Scienze, 90128 Palermo, Italy;
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11
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Tsaban G, Yaskolka Meir A, Zelicha H, Rinott E, Kaplan A, Shalev A, Katz A, Brikner D, Blüher M, Ceglarek U, Stumvoll M, Stampfer MJ, Shai I. Diet-induced Fasting Ghrelin Elevation Reflects the Recovery of Insulin Sensitivity and Visceral Adiposity Regression. J Clin Endocrinol Metab 2022; 107:336-345. [PMID: 34643713 DOI: 10.1210/clinem/dgab681] [Citation(s) in RCA: 8] [Impact Index Per Article: 2.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 01/05/2021] [Indexed: 01/15/2023]
Abstract
CONTEXT Lower fasting ghrelin levels (FGL) are associated with obesity and metabolic syndrome. OBJECTIVE We aimed to explore the dynamics of FGL during weight loss and its metabolic and adiposity-related manifestations beyond weight loss. METHODS This was a secondary analysis of a clinical trial that randomized participants with abdominal obesity/dyslipidemia to 1 of 3 diets: healthy dietary guidelines (HDG), Mediterranean diet (MED), or green-MED diet, all combined with physical activity (PA). Both MED diets were similarly hypocaloric and included 28 g/day walnuts. The green-MED group further consumed green tea (3-4 cups/day) and a Wolffia globosa (Mankai) plant green shake. We measured FGL and quantified body fat depots by magnetic resonance imaging at baseline and after 18 months. RESULTS Among 294 participants (body mass index = 31.3 kg/m2; FGL = 504 ± 208 pg/mL; retention rate = 89.8%), lower FGL was associated with unfavorable cardiometabolic parameters such as higher visceral adipose tissue (VAT), intrahepatic fat, leptin, and blood pressure (P < 0.05 for all; multivariate models). The ∆FGL18-month differed between men (+7.3 ± 26.6%) and women (-9.2% ± 21.3%; P = 0.001). After 18 months of moderate and similar weight loss among the MED groups, FGL increased by 1.3%, 5.4%, and 10.5% in HDG, MED, and green-MED groups, respectively (P = 0.03 for green-MED vs HDG); sex-stratified analysis revealed similar changes in men only. Among men, FGL18-month elevation was associated with favorable changes in insulin resistance profile and VAT regression, after adjusting for relative weight loss (HbA1c: r = -0.216; homeostatic model of insulin resistance: r = -0.154; HDL-c: r = 0.147; VAT: r = -0.221; P < 0.05 for all). Insulin resistance and VAT remained inversely related with FGL elevation beyond that explained by weight loss (residual regression analyses; P < 0.05). CONCLUSION Diet-induced FGL elevation may reflect insulin sensitivity recovery and VAT regression beyond weight loss, specifically among men. Green-MED diet is associated with greater FGL elevation.
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Affiliation(s)
- Gal Tsaban
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Soroka University Medical Center, Beer-Sheva, Israel
| | - Anat Yaskolka Meir
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Hila Zelicha
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Ehud Rinott
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Alon Kaplan
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Aryeh Shalev
- Soroka University Medical Center, Beer-Sheva, Israel
| | - Amos Katz
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
| | - Dov Brikner
- Nuclear Research Center Negev, Department of Medicine, Dimona, Israel
| | - Matthias Blüher
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | - Uta Ceglarek
- Department of Medicine, University of Leipzig, Leipzig, Germany
| | | | - Meir J Stampfer
- Harvard T.H. Chan School of Public Health and Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA
| | - Iris Shai
- Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel
- Harvard T.H. Chan School of Public Health and Channing Division of Network Medicine, Department of Medicine, Harvard Medical School and Brigham and Women's Hospital, Boston, MA, USA
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12
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Ouerghi N, Feki M, Bragazzi NL, Knechtle B, Hill L, Nikolaidis PT, Bouassida A. Ghrelin Response to Acute and Chronic Exercise: Insights and Implications from a Systematic Review of the Literature. Sports Med 2021; 51:2389-2410. [PMID: 34374968 PMCID: PMC8514378 DOI: 10.1007/s40279-021-01518-6] [Citation(s) in RCA: 26] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Accepted: 07/05/2021] [Indexed: 12/15/2022]
Abstract
BACKGROUND Ghrelin is a peptide hormone predominantly produced by the stomach. It exerts a wide range of functions including stimulating growth hormone release and regulating appetite, food intake, and glucose and lipid metabolism. Since physical exercise affects all these aspects, a particular interest is accorded to the relationship between ghrelin and exercise. This systematic review aimed to summarize the current available data on the topic for a better understanding of the relationship. METHODS An extensive computerized search was performed in the PubMed and SPORTDiscus databases for retrieving relevant articles. The search contained the following keywords: ghrelin, appetite-related peptides, gastrointestinal peptides, gastrointestinal hormones, exercise, acute exercise, chronic exercise, training, and physical activity. Studies investigating the effects of acute/chronic exercise on circulating forms of ghrelin were included. RESULTS The initial search identified 840 articles. After screening, 80 articles were included. Despite a heterogeneity of studies and a variability of the findings, the review suggests that acute exercise suppresses acyl ghrelin production regardless of the participants and the exercise characteristics. Long- and very long-term exercise training programs mostly resulted in increased total and des-acyl ghrelin production. The increase is more noticeable in overweight/obese individuals, and is most likely due to weight loss resulting from the training program. CONCLUSION The review suggests that exercise may impact ghrelin production. While the precise mechanisms are unclear, the effects are likely due to blood flow redistribution and weight loss for acute and chronic exercise, respectively. These changes are expected to be metabolically beneficial. Further research is needed for a better understanding of the relationship between ghrelin and exercise.
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Affiliation(s)
- Nejmeddine Ouerghi
- High Institute of Sport and Physical Education of Kef, UR13JS01, University of Jendouba, 7100, Kef, Tunisia.,Faculty of Medicine of Tunis, Rabta Hospital, LR99ES11, University of Tunis El Manar, 1007, Tunis, Tunisia
| | - Moncef Feki
- Faculty of Medicine of Tunis, Rabta Hospital, LR99ES11, University of Tunis El Manar, 1007, Tunis, Tunisia
| | - Nicola Luigi Bragazzi
- Postgraduate School of Public Health, Department of Health Sciences (DISSAL), University of Genoa, 16132, Genoa, Italy
| | - Beat Knechtle
- Medbase St. Gallen Am Vadianplatz, Vadianstrasse 26, 9001, St. Gallen, Switzerland. .,Institute of Primary Care, University of Zurich, Zurich, Switzerland.
| | - Lee Hill
- Division of Gastroenterology and Nutrition, Department of Pediatrics, McMaster University, Hamilton, L8S 4L8, Canada
| | | | - Anissa Bouassida
- High Institute of Sport and Physical Education of Kef, UR13JS01, University of Jendouba, 7100, Kef, Tunisia
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13
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Benedetti S, Moir HJ, Stensel DJ, Thackray AE, Naughton D, Allgrove JE. Effects of moderate to vigorous intensity cycling on appetite, ad libitum energy intake and appetite-related hormones in healthy South Asian and white European men. Appetite 2021; 165:105282. [PMID: 33971288 DOI: 10.1016/j.appet.2021.105282] [Citation(s) in RCA: 0] [Impact Index Per Article: 0] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 11/04/2020] [Revised: 04/17/2021] [Accepted: 04/22/2021] [Indexed: 11/17/2022]
Abstract
Compensatory changes in appetite and energy intake do not appear to occur in the short-term after acute exercise; however, responses have not been compared in South Asians, a group at high risk of central obesity and type 2 diabetes, with white Europeans. This study examined appetite perceptions, energy intake and appetite-related hormones after moderate-to-vigorous intensity cycling in South Asian versus white European men. Fifteen South Asians (mean(SD) 29(8) years; 25.4(4.5) kg m-2) and fifteen white Europeans (33(10) years; 26.1(3.8) kg m-2) matched for age and body mass index completed two 7 h trials (control and exercise). Participants rested throughout both trials apart from completing 60 min cycling at 2-3 h in the exercise trial. A standardised breakfast was consumed at 0 h and an ad libitum buffet meal at 4 h. Appetite perceptions and appetite-related hormones were measured at predetermined intervals. Exercise suppressed acylated ghrelin (d = 0.19, P < 0.001) and increased total peptide YY (PYY) (d = 0.14, P = 0.004), insulin (d = 0.09, P = 0.046) and glucose concentrations (d = 0.31, P < 0.001) (main effect of trial), without stimulating compensatory increases in energy intakes in either group (group-by-trial interactions). South Asians exhibited lower absolute energy intake and higher insulin concentrations than white Europeans (main effect group d ≥ 0.63, P ≤ 0.003), whereas group-by-time interactions revealed lower acylated ghrelin concentrations at 3 and 4 h (d ≥ 0.75, P ≤ 0.038) and higher glucose concentrations at 0.75 and 2 h (d ≥ 0.67, P ≤ 0.008) in South Asian than white European men. These findings demonstrate that acute exercise induces a short-term energy deficit and similar appetite responses in South Asian and white European men.
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Affiliation(s)
- Simone Benedetti
- Applied & Human Sciences, School of Life Sciences, Pharmacy & Chemistry, Kingston University London, Kingston upon Thames KT1 2EE, UK.
| | - Hannah J Moir
- Applied & Human Sciences, School of Life Sciences, Pharmacy & Chemistry, Kingston University London, Kingston upon Thames KT1 2EE, UK.
| | - David J Stensel
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Epinal Way, Loughborough, LE11 3TU, UK; National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK.
| | - Alice E Thackray
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Epinal Way, Loughborough, LE11 3TU, UK; National Institute for Health Research (NIHR) Leicester Biomedical Research Centre, University Hospitals of Leicester NHS Trust and University of Leicester, Leicester, UK.
| | - Declan Naughton
- Applied & Human Sciences, School of Life Sciences, Pharmacy & Chemistry, Kingston University London, Kingston upon Thames KT1 2EE, UK.
| | - Judith E Allgrove
- Applied & Human Sciences, School of Life Sciences, Pharmacy & Chemistry, Kingston University London, Kingston upon Thames KT1 2EE, UK.
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14
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Gupta S, Mitra A. Heal the heart through gut (hormone) ghrelin: a potential player to combat heart failure. Heart Fail Rev 2020; 26:417-435. [PMID: 33025414 DOI: 10.1007/s10741-020-10032-2] [Citation(s) in RCA: 7] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Accepted: 09/21/2020] [Indexed: 12/17/2022]
Abstract
Ghrelin, a small peptide hormone (28 aa), secreted mainly by X/A-like cells of gastric mucosa, is also locally produced in cardiomyocytes. Being an orexigenic factor (appetite stimulant), it promotes release of growth hormone (GH) and exerts diverse physiological functions, viz. regulation of energy balance, glucose, and/or fat metabolism for body weight maintenance. Interestingly, administration of exogenous ghrelin significantly improves cardiac functions in CVD patients as well as experimental animal models of heart failure. Ghrelin ameliorates pathophysiological condition of the heart in myocardial infarction, cardiac hypertrophy, fibrosis, cachexia, and ischemia reperfusion injury. This peptide also exerts significant impact at the level of vasculature leading to lowering high blood pressure and reversal of endothelial dysfunction and atherosclerosis. However, the molecular mechanism of actions elucidating the healing effects of ghrelin on the cardiovascular system is still a matter of conjecture. Some experimental data indicate its beneficial effects via complex cellular cross talks between autonomic nervous system and cardiovascular cells, some other suggest more direct receptor-mediated molecular actions via autophagy or ionotropic regulation and interfering with apoptotic and inflammatory pathways of cardiomyocytes and vascular endothelial cells. Here, in this review, we summarise available recent data to encourage more research to find the missing links of unknown ghrelin receptor-mediated pathways as we see ghrelin as a future novel therapy in cardiovascular protection.
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Affiliation(s)
- Shreyasi Gupta
- Department of Zoology, Triveni Devi Bhalotia College, Raniganj, Paschim Bardhaman, 713347, India
| | - Arkadeep Mitra
- Department of Zoology, City College , 102/1, Raja Rammohan Sarani, Kolkata, 700009, India.
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15
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Gortan Cappellari G, Barazzoni R. Ghrelin forms in the modulation of energy balance and metabolism. Eat Weight Disord 2019; 24:997-1013. [PMID: 30353455 DOI: 10.1007/s40519-018-0599-6] [Citation(s) in RCA: 22] [Impact Index Per Article: 3.7] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/25/2018] [Accepted: 10/16/2018] [Indexed: 02/06/2023] Open
Abstract
Ghrelin is a gastric hormone circulating in acylated (AG) and unacylated (UnAG) forms. This narrative review aims at presenting current emerging knowledge on the impact of ghrelin forms on energy balance and metabolism. AG represents ~ 10% of total plasma ghrelin, has an appetite-stimulating effect and is the only form for which a receptor has been identified. Moreover, other metabolic AG-induced effects have been reported, including the modulation of glucose homeostasis with stimulation of liver gluconeogenesis, the increase of fat mass and the improvement of skeletal muscle mitochondrial function. On the other hand, UnAG has no orexigenic effects, however recent reports have shown that it is directly involved in the modulation of skeletal muscle energy metabolism by improving a cluster of interlinked functions including mitochondrial redox activities, tissue inflammation and insulin signalling and action. These findings are in agreement with human studies which show that UnAG circulating levels are positively associated with insulin sensitivity both in metabolic syndrome patients and in a large cohort from the general population. Moreover, ghrelin acylation is regulated by a nutrient sensor mechanism, specifically set on fatty acids availability. These recent findings consistently point towards a novel independent role of UnAG as a regulator of muscle metabolic pathways maintaining energy status and tissue anabolism. While a specific receptor for UnAG still needs to be identified, recent evidence strongly supports the hypothesis that the modulation of ghrelin-related molecular pathways, including those involved in its acylation, may be a potential novel target in the treatment of metabolic derangements in disease states characterized by metabolic and nutritional complications.Level of evidence Level V, narrative review.
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Affiliation(s)
- Gianluca Gortan Cappellari
- Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
| | - Rocco Barazzoni
- Department of Medical, Surgical and Health Sciences, University of Trieste, Strada di Fiume, 447, 34149, Trieste, Italy.
- Azienda Sanitaria Universitaria Integrata di Trieste (ASUITS), Trieste, Italy.
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16
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Lost in Translation? On the Need for Convergence in Animal and
Human Studies on the Role of Dopamine in Diet-Induced Obesity. CURRENT ADDICTION REPORTS 2019. [DOI: 10.1007/s40429-019-00268-w] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.3] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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17
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Gray SM, Page LC, Tong J. Ghrelin regulation of glucose metabolism. J Neuroendocrinol 2019; 31:e12705. [PMID: 30849212 PMCID: PMC6688917 DOI: 10.1111/jne.12705] [Citation(s) in RCA: 44] [Impact Index Per Article: 7.3] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/05/2018] [Revised: 03/04/2019] [Accepted: 03/05/2019] [Indexed: 12/14/2022]
Abstract
Ghrelin and its receptor, the growth hormone secretagogue receptor 1a (GHSR1a), are implicated in the regulation of glucose metabolism via direct actions in the pancreatic islet, as well as peripheral insulin-sensitive tissues and the brain. Although many studies have explored the role of ghrelin in glucose tolerance and insulin secretion, a complete mechanistic understanding remains to be clarified. This review highlights the local expression and function of ghrelin and GHSR1a in pancreatic islets and how this axis may modulate insulin secretion from pancreatic β-cells. Additionally, we discuss the effect of ghrelin on in vivo glucose metabolism in rodents and humans, as well as the metabolic circumstances under which the action of ghrelin may predominate.
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Affiliation(s)
- Sarah. M. Gray
- Duke Molecular Physiology Institute, Duke University, Durham, NC 27701
| | - Laura C. Page
- Division of Endocrinology, Department of Pediatrics, Duke University, Durham, NC 27701
| | - Jenny Tong
- Duke Molecular Physiology Institute, Duke University, Durham, NC 27701
- Division of Endocrinology, Department of Pediatrics, Duke University, Durham, NC 27701
- Division of Endocrinology, Metabolism, and Nutrition, Department of Medicine, Duke University, Durham, NC 27701
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18
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Li YY, Lu XZ, Yang XX, Wang H, Geng HY, Gong G, Zhan YY, Kim HJ, Yang ZJ. GHRL Gene Leu72Met Polymorphism and Type 2 Diabetes Mellitus: A Meta-Analysis Involving 8,194 Participants. Front Endocrinol (Lausanne) 2019; 10:559. [PMID: 31440212 PMCID: PMC6694458 DOI: 10.3389/fendo.2019.00559] [Citation(s) in RCA: 9] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 05/10/2018] [Accepted: 07/29/2019] [Indexed: 12/22/2022] Open
Abstract
Background: Although many studies indicate a positive correlation between GHRL gene Leu72Met polymorphism and an increased susceptibility to type 2 diabetes mellitus (T2DM), inconsistencies between independent studies still remain. Objective: Considering the inconsistencies between them, we have performed the current meta-analysis study. The objective of this study is to better examine the correlation of the GHRL gene Leu72Met polymorphism and T2DM. Methods: The current meta-analysis, involving 8,194 participants from 11 independent studies, was performed. A fixed effect model was used to evaluate the pooled odds ratios (ORs) and the corresponding 95% confidence intervals (95% CIs). Results: A significant association was found between T2DM and GHRL gene Leu72Met polymorphism under recessive (OR: 1.33, 95% CI: 1.01-1.76, P = 0.04), and homozygous genetic models (OR: 1.34, 95% CI: 1.01-1.78, P = 0.04) in the whole population. The correlation was more distinct in our subgroup analysis of the Chinese population under recessive (OR: 1.52, 95% CI: 1.07-2.15, P = 0.02), dominant (OR: 1.70, 95% CI: 1.38-2.10, P < 0.00001), additive (OR: 1.16, 95% CI: 1.02-1.33, P = 0.02), and homozygous genetic models (OR: 1.54, 95% CI: 1.07-2.20, P = 0.02). Conclusions: In short, GHRL gene Leu72Met polymorphism was significantly correlated with increased T2DM risk, particularly in the Chinese population. Individuals carrying the Met72 allele of GHRL Leu72Met gene polymorphism, particularly those of Chinese ancestry, may be more susceptible to developing T2DM disease.
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Affiliation(s)
- Yan-yan Li
- Clinical Research Center, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
- *Correspondence: Yan-yan Li
| | - Xin-zheng Lu
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Xin-xing Yang
- Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hui Wang
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hong-yu Geng
- Department of Intensive Care Unit, Baoding First Center Hospital, Baoding, China
| | - Ge Gong
- Department of Gerontology, Nanjing General Hospital of Nanjing Military Command, Nanjing, China
| | - Yi-yang Zhan
- Department of Gerontology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
| | - Hyun Jun Kim
- Department of Physiology, University of Cincinnati, Cincinnati, OH, United States
| | - Zhi-jian Yang
- Department of Cardiology, First Affiliated Hospital of Nanjing Medical University, Nanjing, China
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19
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Corbin KD, Driscoll KA, Pratley RE, Smith SR, Maahs DM, Mayer-Davis EJ. Obesity in Type 1 Diabetes: Pathophysiology, Clinical Impact, and Mechanisms. Endocr Rev 2018; 39:629-663. [PMID: 30060120 DOI: 10.1210/er.2017-00191] [Citation(s) in RCA: 158] [Impact Index Per Article: 22.6] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 06/21/2018] [Indexed: 02/07/2023]
Abstract
There has been an alarming increase in the prevalence of obesity in people with type 1 diabetes in recent years. Although obesity has long been recognized as a major risk factor for the development of type 2 diabetes and a catalyst for complications, much less is known about the role of obesity in the initiation and pathogenesis of type 1 diabetes. Emerging evidence suggests that obesity contributes to insulin resistance, dyslipidemia, and cardiometabolic complications in type 1 diabetes. Unique therapeutic strategies may be required to address these comorbidities within the context of intensive insulin therapy, which promotes weight gain. There is an urgent need for clinical guidelines for the prevention and management of obesity in type 1 diabetes. The development of these recommendations will require a transdisciplinary research strategy addressing metabolism, molecular mechanisms, lifestyle, neuropsychology, and novel therapeutics. In this review, the prevalence, clinical impact, energy balance physiology, and potential mechanisms of obesity in type 1 diabetes are described, with a special focus on the substantial gaps in knowledge in this field. Our goal is to provide a framework for the evidence base needed to develop type 1 diabetes-specific weight management recommendations that account for the competing outcomes of glycemic control and weight management.
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Affiliation(s)
- Karen D Corbin
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida
| | - Kimberly A Driscoll
- Department of Pediatrics, School of Medicine, University of Colorado Denver, Aurora, Colorado.,Barbara Davis Center for Diabetes, Aurora, Colorado
| | - Richard E Pratley
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida
| | - Steven R Smith
- Translational Research Institute for Metabolism and Diabetes, Florida Hospital, Orlando, Florida
| | - David M Maahs
- Division of Pediatric Endocrinology, Department of Pediatrics, Stanford University, Stanford, California
| | - Elizabeth J Mayer-Davis
- Department of Nutrition, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina.,Department of Medicine, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
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20
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Abstract
The obesity epidemic continues to escalate each year in the United States more than anywhere else in the world. The existing pharmaceutical and other nonsurgical treatments for morbid obesity produce suboptimal physiologic outcomes compared with those of Roux-en-Y gastric bypass (RYGB) surgery. RYGB has been the gold standard of bariatric surgery because the beneficial long-term outcomes, which include sustainable weight loss and type 2 diabetes mellitus (T2DM) resolution, are far superior to those obtained with other bariatric surgeries. However, the current understanding of RYGB's mechanisms of actions remains limited and incomplete. There is an urgent need to understand these mechanisms as gaining this knowledge may lead to the development of innovative and less invasive procedures and/or medical devices, which can mirror the favorable outcomes of RYGB surgery. In this review, we highlight current observations of the metabolic and physiologic events following RYGB, with a particular focus on the role of the anatomical reconfiguration of the gastrointestinal tract after RYGB.
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Affiliation(s)
- Martin L Yarmush
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Burn Hospital for Children, Boston, Massachusetts 02114;
| | - Matthew D'Alessandro
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Burn Hospital for Children, Boston, Massachusetts 02114;
| | - Nima Saeidi
- Center for Engineering in Medicine, Department of Surgery, Massachusetts General Hospital, Harvard Medical School, and Shriners Burn Hospital for Children, Boston, Massachusetts 02114;
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21
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Kang SJ, Kim JH, Gang Z, Yook YS, Yoon JR, Ha GC, Ko KJ. Effects of 12-week circuit exercise program on obesity index, appetite regulating hormones, and insulin resistance in middle-aged obese females. J Phys Ther Sci 2018; 30:169-173. [PMID: 29410591 PMCID: PMC5788800 DOI: 10.1589/jpts.30.169] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.9] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/21/2017] [Accepted: 10/30/2017] [Indexed: 02/05/2023] Open
Abstract
[Purpose] The purpose of this study is to investigate the effects of circuit exercise on
obesity index, appetite regulating hormones and insulin resistance in middle-aged obese
women. [Subjects and Methods] The subjects of this study were 26 obese middle-aged women
who were selected among participants in exercise class at K Region Health Promotion Center
in South Korea and were randomly assigned to the exercise group (n=13; age 50.15 ± 3.82, %
body fat 38.79 ± 3.28) and the control group (n=13; age 49.84 ± 2.96, % body fat 37.46 ±
2.51). Circuit exercise consisted of aerobic exercise and resistance exercise for 5 weeks
and 50 minutes for 12 weeks. Before and after exercise we measured obesity index, leptin,
ghrelin, fasting blood glucose, insulin, and insulin resistance in all subjects. A
repeated-measured two-way of variance was performed for comparison of the treatment
effects between the exercise and control groups. [Results] Body weight, BMI, and body fat
percentage of obese index decreased significantly. Leptin of dietary regulation hormone
was significantly decreased and ghrelin was significantly increased. Insulin and insulin
resistance was significantly decreased. [Conclusion] Circuit exercise can be viewed as an
effective exercise program to induce changes in appetite regulating hormones and to
improve insulin resistance by mechanisms of energy homeostasis by weight loss.
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Affiliation(s)
- Seol-Jung Kang
- Department of Physical Education, Changwon National University, Republic of Korea
| | - Jong-Hyu Kim
- Health Care Center, Department of Preventive Medicine, Chonbuk National University, Republic of Korea
| | - Zhao Gang
- Department of Physical Education, Shenzhen University, China
| | - Young-Sook Yook
- Department of Exercise Rehabilitation Welfare, Sungshin Women's University, Republic of Korea
| | - Jea-Ryang Yoon
- Department of Physical Education, Korea National Sport University, Republic of Korea
| | - Gi-Chul Ha
- Department of Physical Education, Korea National Sport University, Republic of Korea
| | - Kwang-Jun Ko
- Department of Sports Medicine, National Health Fitness Center: 424 Olympicro, Songpagu, Seoul 05540, Republic of Korea
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22
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Sominsky L, Hodgson DM, McLaughlin EA, Smith R, Wall HM, Spencer SJ. Linking Stress and Infertility: A Novel Role for Ghrelin. Endocr Rev 2017; 38:432-467. [PMID: 28938425 DOI: 10.1210/er.2016-1133] [Citation(s) in RCA: 34] [Impact Index Per Article: 4.3] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 11/17/2016] [Accepted: 07/24/2017] [Indexed: 12/23/2022]
Abstract
Infertility affects a remarkable one in four couples in developing countries. Psychological stress is a ubiquitous facet of life, and although stress affects us all at some point, prolonged or unmanageable stress may become harmful for some individuals, negatively impacting on their health, including fertility. For instance, women who struggle to conceive are twice as likely to suffer from emotional distress than fertile women. Assisted reproductive technology treatments place an additional physical, emotional, and financial burden of stress, particularly on women, who are often exposed to invasive techniques associated with treatment. Stress-reduction interventions can reduce negative affect and in some cases to improve in vitro fertilization outcomes. Although it has been well-established that stress negatively affects fertility in animal models, human research remains inconsistent due to individual differences and methodological flaws. Attempts to isolate single causal links between stress and infertility have not yet been successful due to their multifaceted etiologies. In this review, we will discuss the current literature in the field of stress-induced reproductive dysfunction based on animal and human models, and introduce a recently unexplored link between stress and infertility, the gut-derived hormone, ghrelin. We also present evidence from recent seminal studies demonstrating that ghrelin has a principal role in the stress response and reward processing, as well as in regulating reproductive function, and that these roles are tightly interlinked. Collectively, these data support the hypothesis that stress may negatively impact upon fertility at least in part by stimulating a dysregulation in ghrelin signaling.
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Affiliation(s)
- Luba Sominsky
- School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
| | - Deborah M Hodgson
- School of Psychology, Faculty of Science and IT, The University of Newcastle, New South Wales 2308, Australia
| | - Eileen A McLaughlin
- School of Biological Sciences, Faculty of Science, The University of Auckland, Auckland 1010, New Zealand.,School of Environmental & Life Sciences, Faculty of Science and IT, The University of Newcastle, New South Wales 2308, Australia
| | - Roger Smith
- Mothers and Babies Research Centre, Hunter Medical Research Institute, Lookout Road, New Lambton Heights, New South Wales 2305, Australia.,Priority Research Centre in Reproductive Science, The University of Newcastle, New South Wales 2308, Australia
| | - Hannah M Wall
- School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
| | - Sarah J Spencer
- School of Health and Biomedical Sciences, RMIT University, Melbourne, Victoria 3083, Australia
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23
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Gokulakrishnan K, Ranjani H, Weber MB, Pandey GK, Anjana RM, Balasubramanyam M, Prabhakaran D, Tandon N, Narayan KM, Mohan V. Effect of lifestyle improvement program on the biomarkers of adiposity, inflammation and gut hormones in overweight/obese Asian Indians with prediabetes. Acta Diabetol 2017; 54:843-852. [PMID: 28620678 DOI: 10.1007/s00592-017-1015-9] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.8] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 02/13/2017] [Accepted: 06/03/2017] [Indexed: 11/30/2022]
Abstract
AIMS While lifestyle modification is known to offer several metabolic benefits, there is paucity of comprehensive data on changes in biomarkers of adiposity, inflammation as well as gut hormones. We investigated these biomarkers in overweight/obese individuals with prediabetes randomized to either 4 months of a lifestyle improvement program or standard care and followed them up for a year. METHODS Participants [standard care and intervention arm (n = 75 each)] were randomly selected from the Diabetes Community Lifestyle Improvement Program trial. Glycemic and lipid control and anthropometric measurements were assessed by standard protocols. Adipokines, inflammatory markers and gut hormones were measured using multiplex and standard ELISA kits. RESULTS Along with modest benefits in primary outcomes (glycemic and lipid control and weight reduction), participants in the intervention group showed significant reductions (p < 0.001) in plasma levels of leptin (17.6%), TNF-α (35%), IL-6 (33.3%), MCP-1 (22.3%) and PYY (28.3%) and increased levels of adiponectin (33.1%) and ghrelin (23.6%) at the end of 4 months of lifestyle intervention. The changes were independent of weight and persisted even at 1 year of follow-up. In contrast, participants from the standard care arm did not show any statistically significant improvements on the above parameters. CONCLUSIONS Participants who underwent an intensive lifestyle improvement program showed metabolic benefits as well as favorable beneficial changes in systemic levels of adipokines, cytokines and gut hormones, not only during the intervention period, but also during 12-month follow-up period.
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Affiliation(s)
- Kuppan Gokulakrishnan
- Department of Research Biochemistry, Madras Diabetes Research Foundation (MDRF), 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India.
| | - Harish Ranjani
- Department of Research Biochemistry, Madras Diabetes Research Foundation (MDRF), 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India
| | | | - Gautam Kumar Pandey
- Department of Research Biochemistry, Madras Diabetes Research Foundation (MDRF), 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India
| | - Ranjit Mohan Anjana
- Department of Research Biochemistry, Madras Diabetes Research Foundation (MDRF), 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India
| | - Muthuswamy Balasubramanyam
- Department of Research Biochemistry, Madras Diabetes Research Foundation (MDRF), 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India
| | - Dorairaj Prabhakaran
- Public Health Foundation of India (PHFI), Centre for Chronic Disease Control (CCDC), New Delhi, India
| | - Nikhil Tandon
- Public Health Foundation of India (PHFI), Centre for Chronic Disease Control (CCDC), New Delhi, India
| | | | - Viswanathan Mohan
- Department of Research Biochemistry, Madras Diabetes Research Foundation (MDRF), 4, Conran Smith Road, Gopalapuram, Chennai, 600 086, India
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24
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Douglas JA, King JA, Clayton DJ, Jackson AP, Sargeant JA, Thackray AE, Davies MJ, Stensel DJ. Acute effects of exercise on appetite, ad libitum energy intake and appetite-regulatory hormones in lean and overweight/obese men and women. Int J Obes (Lond) 2017; 41:1737-1744. [PMID: 28769121 PMCID: PMC5729348 DOI: 10.1038/ijo.2017.181] [Citation(s) in RCA: 71] [Impact Index Per Article: 8.9] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/31/2017] [Revised: 07/13/2017] [Accepted: 07/14/2017] [Indexed: 02/07/2023]
Abstract
BACKGROUND Acute exercise does not elicit compensatory changes in appetite parameters in lean individuals; however, less is known about responses in overweight individuals. This study compared the acute effects of moderate-intensity exercise on appetite, energy intake and appetite-regulatory hormones in lean and overweight/obese individuals. METHODS Forty-seven healthy lean (n=22, 11 females; mean (s.d.) 37.5 (15.2) years; 22.4 (1.5) kg m-2) and overweight/obese (n=25, 11 females; 45.0 (12.4) years, 29.2 (2.9) kg m-2) individuals completed two, 8 h trials (exercise and control). In the exercise trial, participants completed 60 min treadmill exercise (59 (4)% peak oxygen uptake) at 0-1 h and rested thereafter while participants rested throughout the control trial. Appetite ratings and concentrations of acylated ghrelin, peptide YY (PYY) and glucagon-like peptide-1 (GLP-1) were measured at predetermined intervals. Standardised meals were consumed at 1.5 and 4 h and an ad libitum buffet meal was provided at 7 h. RESULTS Exercise suppressed appetite (95% confidence interval (CI) -3.1 to -0.5 mm, P=0.01), and elevated delta PYY (95% CI 10 to 17 pg ml-1, P<0.001) and GLP-1 (95% CI 7 to 10 pmol l-1, P<0.001) concentrations. Delta acylated ghrelin concentrations (95% CI -5 to 3 pg ml-1, P=0.76) and ad libitum energy intake (95% CI -391 to 346 kJ, P=0.90) were similar between trials. Subjective and hormonal appetite parameters and ad libitum energy intake were similar between lean and overweight/obese individuals (P⩾0.27). The exercise-induced elevation in delta GLP-1 was greater in overweight/obese individuals (trial-by-group interaction P=0.01), whereas lean individuals exhibited a greater exercise-induced increase in delta PYY (trial-by-group interaction P<0.001). CONCLUSIONS Acute moderate-intensity exercise transiently suppressed appetite and increased PYY and GLP-1 in the hours after exercise without stimulating compensatory changes in appetite in lean or overweight/obese individuals. These findings underscore the ability of exercise to induce a short-term energy deficit without any compensatory effects on appetite regardless of weight status.
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Affiliation(s)
- J A Douglas
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.,Institute of Cancer and Genomic Sciences, University of Birmingham, Birmingham, UK
| | - J A King
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - D J Clayton
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - A P Jackson
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK.,School of Biological Sciences, University of Nottingham, Sutton Bonington, UK
| | - J A Sargeant
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - A E Thackray
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
| | - M J Davies
- Diabetes Research Centre, University of Leicester, Leicester General Hospital, Leicester, UK
| | - D J Stensel
- National Centre for Sport and Exercise Medicine, School of Sport, Exercise and Health Sciences, Loughborough University, Loughborough, UK
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25
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Santiago-Fernández C, García-Serrano S, Tome M, Valdes S, Ocaña-Wilhelmi L, Rodríguez-Cañete A, Tinahones FJ, García-Fuentes E, Garrido-Sánchez L. Ghrelin levels could be involved in the improvement of insulin resistance after bariatric surgery. ACTA ACUST UNITED AC 2017; 64:355-362. [PMID: 28745606 DOI: 10.1016/j.endinu.2017.05.002] [Citation(s) in RCA: 18] [Impact Index Per Article: 2.3] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 02/23/2017] [Revised: 05/04/2017] [Accepted: 05/11/2017] [Indexed: 12/19/2022]
Abstract
BACKGROUND AND OBJECTIVE Ghrelin is a gastrointestinal peptide involved in regulation of body weight and energy balance. However, its behavior after bariatric surgery and its relationship to insulin resistance are still controversial. A simultaneous assessment was made of the association between changes in ghrelin levels and different variables after three types of bariatric surgery. PATIENTS AND METHODS Ghrelin levels were measured in 103 morbidly obese subjects before and 6 months after bariatric surgery (Roux-en-Y gastric bypass (RYGB), biliopancreatic diversion of Scopinaro (BPD), and sleeve gastrectomy (SG)), and in 21 non-obese subjects. RESULTS Ghrelin levels increased after RYGB (p<0.05), were unchanged after BPD, and decreased after SG (p<0.05). The percent change in ghrelin levels (Δ-ghrelin) was associated to the type of surgery in a multiple linear regression model (p=0.017). When the same analysis was only performed in subjects in whom the gastric fundus was maintained (RYGB and BPD), Δ-ghrelin was negatively associated to Δ-HOMA-IR (p=0.001). In morbidly obese subjects who underwent RYGB and BPD, the odds ratio of a lower Δ-HOMA-IR in patients with Δ-ghrelin in the Q1 quartile versus those with Δ-ghrelin in the Q4 quartile was 8.74 (1.73-44.06) (p=0.009). CONCLUSIONS Changes in ghrelin levels after bariatric surgery are associated to the presence or absence of the gastric fundus. After bariatric surgery, the decrease in insulin resistance was associated to increased ghrelin levels in procedures in which the fundus is not excluded.
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Affiliation(s)
- Concepción Santiago-Fernández
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain
| | - Sara García-Serrano
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Malaga, Spain
| | - Mónica Tome
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain
| | - Sergio Valdes
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Málaga, Spain; CIBER de Diabetes y Enfermedades Metabólicas Asociadas (CIBERDEM), Malaga, Spain
| | - Luis Ocaña-Wilhelmi
- Unidad de Gestión Clínica de Cirugía General, Digestiva y Transplantes, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain
| | - Alberto Rodríguez-Cañete
- Unidad de Gestión Clínica de Cirugía General, Digestiva y Transplantes, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Regional Universitario, Málaga, Spain
| | - Francisco J Tinahones
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Málaga, Spain.
| | - Eduardo García-Fuentes
- CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Málaga, Spain; Unidad de Gestión Clínica de Aparato Digestivo, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Málaga, Spain.
| | - Lourdes Garrido-Sánchez
- Unidad de Gestión Clínica de Endocrinología y Nutrición, Instituto de Investigación Biomédica de Málaga (IBIMA), Hospital Universitario Virgen de la Victoria, Universidad de Málaga, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBEROBN), Málaga, Spain
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26
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Alamri BN, Shin K, Chappe V, Anini Y. The role of ghrelin in the regulation of glucose homeostasis. Horm Mol Biol Clin Investig 2017; 26:3-11. [PMID: 27235674 DOI: 10.1515/hmbci-2016-0018] [Citation(s) in RCA: 50] [Impact Index Per Article: 6.3] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/28/2016] [Accepted: 05/08/2016] [Indexed: 12/16/2022]
Abstract
Ghrelin is a 28-amino acid (aa) stomach-derived peptide discovered in 1999 as the endogenous ligand for growth hormone secretagogue-receptor (GHS-R). Ghrelin-producing cells constitute a distinct group of endocrine cells dispersed throughout the gastric mucosa and to a lesser extent in the small intestine and the endocrine pancreas. Ghrelin plasma levels rise during fasting and chronic caloric restriction to stimulate food intake and fat storage and to prevent life-threatening falls in blood glucose. Plasma ghrelin levels decrease after a meal is consumed and in conditions of energy surplus (such as obesity). Ghrelin has emerged as a key player in the regulation of appetite and energy homeostasis. Ghrelin achieves these functions through binding the ghrelin receptor GHS-R in appetite-regulating neurons and in peripheral metabolic organs including the endocrine pancreas. Ghrelin levels are negatively correlated with body mass index (BMI) and insulin resistance. In addition, ghrelin secretion is impaired in obesity and insulin resistance. Several studies highlight an important role for ghrelin in glucose homeostasis. Genetic, immunological, and pharmacological blockade of ghrelin signaling resulted in improved glucose tolerance and insulin sensitivity. Furthermore, exogenous ghrelin administration was shown to decrease glucose-induced insulin release and increase glucose level in both humans and rodents. GHS-R was shown to be expressed in pancreatic β-cells and ghrelin suppressed insulin release via a Ca2+-mediated pathway. In this review, we provide a detailed summary of recent advances in the field that focuses on the role of insulin and insulin resistance in the regulation of ghrelin secretion and on the role of ghrelin in glucose-stimulated insulin secretion (GSIS).
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27
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Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals. Br J Nutr 2017; 117:48-55. [PMID: 28115026 DOI: 10.1017/s0007114516004475] [Citation(s) in RCA: 28] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/11/2022]
Abstract
Obesity is undoubtedly caused by a chronic positive energy balance. However, the early metabolic and hormonal responses to overeating are poorly described. This study determined glycaemic control and selected gut hormone responses to nutrient intake before and after 7 d of high-fat overfeeding. Nine healthy individuals (five males, four females) performed a mixed meal tolerance test (MTT) before and after consuming a high-fat (65 %), high-energy (+50 %) diet for 7 d. Measurements of plasma glucose, NEFA, acylated ghrelin, glucagon-like peptide-1 (GLP-1), gastric inhibitory polypeptide (GIP) and serum insulin were taken before (fasting) and at 30-min intervals throughout the 180-min MTT (postprandial). Body mass increased by 0·79 (sem 0·14) kg after high-fat overfeeding (P<0·0001), and BMI increased by 0·27 (sem 0·05) kg/m2 (P=0·002). High-fat overfeeding also resulted in an 11·6 % increase in postprandial glucose AUC (P=0·007) and a 25·9 % increase in postprandial insulin AUC (P=0·005). Acylated ghrelin, GLP-1 and GIP responses to the MTT were all unaffected by the high-fat, high-energy diet. These findings demonstrate that even brief periods of overeating are sufficient to disrupt glycaemic control. However, as the postprandial orexigenic (ghrelin) and anorexigenic/insulintropic (GLP-1 and GIP) hormone responses were unaffected by the diet intervention, it appears that these hormones are resistant to short-term changes in energy balance, and that they do not play a role in the rapid reduction in glycaemic control.
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28
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Serum ghrelin levels in patients with Behcet's disease. Postepy Dermatol Alergol 2016; 33:450-456. [PMID: 28035223 PMCID: PMC5183784 DOI: 10.5114/ada.2016.63884] [Citation(s) in RCA: 2] [Impact Index Per Article: 0.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/23/2015] [Accepted: 11/12/2015] [Indexed: 01/23/2023] Open
Abstract
Introduction Behcet’s disease (BD) is a chronic, relapsing, systemic vasculitis of unknown etiology. Aim To measure serum ghrelin levels in BD patients and healthy controls and to investigate its association with metabolic syndrome (MetS). Material and methods Thirty BD patients and 30 healthy individuals were enrolled in the study. Ghrelin levels were measured in blood samples using ELISA. Results The mean serum ghrelin level in BD patients (28.57 ±14.04) was significantly lower compared to healthy controls (40.72 ±23.21) (p = 0.01). The mean serum ghrelin level in BD patients who had MetS (24.18 ±12.73) was lower compared to BD patients who did not have MetS (30.77 ±14.45), but this difference was not significant (p > 0.05). Conclusions Ghrelin levels were lower in BD patients compared to healthy controls. There was no association between reduced ghrelin levels and MetS; however, there was a negative correlation between ghrelin levels and disease activity.
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29
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Heshmat R, Shafiee G, Qorbani M, Azizi-Soleiman F, Djalalinia S, Esmaeil Motlagh M, Ardalan G, Ahadi Z, Safari O, Safiri S, Kelishadi R. Association of ghrelin with cardiometabolic risk factors in Iranian adolescents: the CASPIAN-III study. J Cardiovasc Thorac Res 2016; 8:107-112. [PMID: 27777695 PMCID: PMC5075358 DOI: 10.15171/jcvtr.2016.23] [Citation(s) in RCA: 13] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 03/12/2016] [Accepted: 08/29/2016] [Indexed: 12/02/2022] Open
Abstract
Introduction: Current evidence suggests that ghrelin could contribute to the development of metabolic syndrome (MetS) in adults, but limited experience exists in adolescents. This study aims to explore the association of ghrelin levels with the MetS components among Iranian adolescents.
Methods: In this case-control study, 32 adolescents with MetS and 148 healthy controls were selected randomly from the childhood and Adolescence Surveillance and Prevention of Adult Non communicable disease (CASPIAN-III) study. MetS was defined according to the Adult Treatment Panel III (ATP III) criteria modified for children and adolescents. Anthropometric measures (including body mass index [BMI], waist circumference [WC] and waist to height ratio [WHtR]), blood pressure (BP) and biochemical data (including fasting blood sugar [FBS], triglyceride [TG], high-density lipoprotein cholesterol [HDL-C], low-density lipoprotein cholesterol [LDL-C], total cholesterol [TC] and gerlin) were measured.
Results: Total ghrelin level was significantly higher in students without MetS compared to those
with MetS (748.89 ± 85.04 vs. 728.72 ± 90.36 [pg/mL]; P < 0.001). Significant negative correlations
were seen between ghrelin levels and BMI, WC, WHtR, TG, and TC. Ghrelin had also relatively
strong inverse correlations with FBS (r = −0.59, P< 0.001), LDL-C (r = −0.56, P < 0.001), and
positive correlation with HDL-C (r = 0.60, P < 0.001). Compared with the children with MetS, in
those without MetS, ghrelin was significantly associated with HDL-C and LDL-C. A decreasing
trend was observed in the mean ghrelin level across increasing number of MetS components (P
for trend <0.001).
Conclusion: We observed a relationship between ghrelin concentration and MetS components in adolescents.
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Affiliation(s)
- Ramin Heshmat
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Gita Shafiee
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Mostafa Qorbani
- Department of Community Medicine, Alborz University of Medical Sciences, Karaj, Iran ; Endocrinology and Metabolism Research Center, Endocrinology and Metabolism Clinical Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Fatemeh Azizi-Soleiman
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non- Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Shirin Djalalinia
- Development of Research & Technology Center, Deputy of Research and Technology, Ministry of Health and Medical Education, Tehran, Iran
| | | | - Gelayol Ardalan
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non- Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
| | - Zeinab Ahadi
- Chronic Diseases Research Center, Endocrinology and Metabolism Population Sciences Institute, Tehran University of Medical Sciences, Tehran, Iran
| | - Omid Safari
- Department of Pediatrics, Alborz University of Medical Sciences, Karaj, Iran
| | - Saeid Safiri
- Managerial Epidemiology Research Center, Department of Public Health, School of Nursing and Midwifery, Maragheh University of Medical Sciences, Maragheh, Iran
| | - Roya Kelishadi
- Department of Pediatrics, Child Growth and Development Research Center, Research Institute for Primordial Prevention of Non- Communicable Disease, Isfahan University of Medical Sciences, Isfahan, Iran
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30
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Razzaghy-Azar M, Nourbakhsh M, Pourmoteabed A, Nourbakhsh M, Ilbeigi D, Khosravi M. An Evaluation of Acylated Ghrelin and Obestatin Levels in Childhood Obesity and Their Association with Insulin Resistance, Metabolic Syndrome, and Oxidative Stress. J Clin Med 2016; 5:61. [PMID: 27348010 PMCID: PMC4961992 DOI: 10.3390/jcm5070061] [Citation(s) in RCA: 25] [Impact Index Per Article: 2.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 04/20/2016] [Revised: 05/16/2016] [Accepted: 06/01/2016] [Indexed: 12/27/2022] Open
Abstract
BACKGROUND Ghrelin is a 28-amino acid peptide with an orexigenic property, which is predominantly produced by the stomach. Acylated ghrelin is the active form of this hormone. Obestatin is a 23-amino acid peptide which is produced by post-translational modification of a protein precursor that also produces ghrelin. Obestatin has the opposite effect of ghrelin on food intake. The aim of this study was to evaluate acylated ghrelin and obestatin levels and their ratio in obese and normal-weight children and adolescents, and their association with metabolic syndrome (MetS) parameters. METHODS Serum acyl-ghrelin, obestatin, leptin, insulin, fasting plasma glucose (FPG), lipid profile, and malondialdehyde (MDA) were evaluated in 73 children and adolescents (42 obese and 31 control). Insulin resistance was calculated by a homeostasis model assessment of insulin resistance (HOMA-IR). MetS was determined according to IDF criteria. RESULTS Acyl-ghrelin levels were significantly lower in obese subjects compared to the control group and lower in obese children with MetS compared to obese subjects without MetS. Obestatin was significantly higher in obese subjects compared to that of the control, but it did not differ significantly among those with or without MetS. Acyl-ghrelin to obestatin ratio was significantly lower in obese subjects compared to that in normal subjects. Acyl-ghrelin showed significant negative and obestatin showed significant positive correlations with body mass index (BMI), BMI Z-score, leptin, insulin, and HOMA-IR. Acyl-ghrelin had a significant negative correlation with MDA as an index of oxidative stress. CONCLUSION Ghrelin is decreased and obestatin is elevated in obesity. Both of these hormones are associated with insulin resistance, and ghrelin is associated with oxidative stress. The balance between ghrelin and obestatin seems to be disturbed in obesity.
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Affiliation(s)
- Maryam Razzaghy-Azar
- Metabolic Disorders Research Center, Endocrinology and Metabolism Molecular-Cellular Sciences Institute, Tehran University of Medical Sciences, 1411715851 Tehran, Iran.
- H. Aliasghar Hospital, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
| | - Mitra Nourbakhsh
- Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
| | | | - Mona Nourbakhsh
- H. Aliasghar Hospital, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
| | - Davod Ilbeigi
- Department of Biochemistry, School of Medicine, Tehran University of Medical Sciences, 1417614418 Tehran, Iran.
| | - Mohsen Khosravi
- Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, 1449614535 Tehran, Iran.
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31
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Robberecht H, Hermans N. Biomarkers of Metabolic Syndrome: Biochemical Background and Clinical Significance. Metab Syndr Relat Disord 2016; 14:47-93. [PMID: 26808223 DOI: 10.1089/met.2015.0113] [Citation(s) in RCA: 20] [Impact Index Per Article: 2.2] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/06/2023] Open
Abstract
Biomarkers of the metabolic syndrome are divided into four subgroups. Although dividing them in groups has some limitations, it can be used to draw some conclusions. In a first part, the dyslipidemias and markers of oxidative stress are discussed, while inflammatory markers and cardiometabolic biomarkers are reviewed in a second part. For most of them, the biochemical background and clinical significance are discussed, although here also a well-cut separation cannot always be made. Altered levels cannot always be claimed as the cause, risk, or consequence of the syndrome. Several factors are interrelated to each other and act in a concerted, antagonistic, synergistic, or modulating way. Most important conclusions are summarized at the end of every reviewed subgroup. Genetic biomarkers or influences of various food components on concentration levels are not included in this review article.
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Affiliation(s)
- Harry Robberecht
- Department of Pharmaceutical Sciences, NatuRA (Natural Products and Food Research and Analysis), University of Antwerp , Wilrijk, Antwerp, Belgium
| | - Nina Hermans
- Department of Pharmaceutical Sciences, NatuRA (Natural Products and Food Research and Analysis), University of Antwerp , Wilrijk, Antwerp, Belgium
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Srikanthan K, Feyh A, Visweshwar H, Shapiro JI, Sodhi K. Systematic Review of Metabolic Syndrome Biomarkers: A Panel for Early Detection, Management, and Risk Stratification in the West Virginian Population. Int J Med Sci 2016; 13:25-38. [PMID: 26816492 PMCID: PMC4716817 DOI: 10.7150/ijms.13800] [Citation(s) in RCA: 289] [Impact Index Per Article: 32.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/09/2015] [Accepted: 11/09/2015] [Indexed: 12/22/2022] Open
Abstract
INTRODUCTION Metabolic syndrome represents a cluster of related metabolic abnormalities, including central obesity, hypertension, dyslipidemia, hyperglycemia, and insulin resistance, with central obesity and insulin resistance in particular recognized as causative factors. These metabolic derangements present significant risk factors for cardiovascular disease, which is commonly recognized as the primary clinical outcome, although other outcomes are possible. Metabolic syndrome is a progressive condition that encompasses a wide array of disorders with specific metabolic abnormalities presenting at different times. These abnormalities can be detected and monitored via serum biomarkers. This review will compile a list of promising biomarkers that are associated with metabolic syndrome and this panel can aid in early detection and management of metabolic syndrome in high risk populations, such as in West Virginia. METHODS A literature review was conducted using PubMed, Science Direct, and Google Scholar to search for markers related to metabolic syndrome. Biomarkers searched included adipokines (leptin, adiponectin), neuropeptides (ghrelin), pro-inflammatory cytokines (IL-6, TNF-α), anti-inflammatory cytokines (IL-10), markers of antioxidant status (OxLDL, PON-1, uric acid), and prothrombic factors (PAI-1). RESULTS According to the literature, the concentrations of pro-inflammatory cytokines (IL-6, TNF-α), markers of pro-oxidant status (OxLDL, uric acid), and prothrombic factors (PAI-1) were elevated in metabolic syndrome. Additionally, leptin concentrations were found to be elevated in metabolic syndrome as well, likely due to leptin resistance. In contrast, concentrations of anti-inflammatory cytokines (IL-10), ghrelin, adiponectin, and antioxidant factors (PON-1) were decreased in metabolic syndrome, and these decreases also correlated with specific disorders within the cluster. CONCLUSION Based on the evidence presented within the literature, the aforementioned biomarkers correlate significantly with metabolic syndrome and could provide a minimally-invasive means for early detection and specific treatment of these disorders. Further research is encouraged to determine the efficacy of applying these biomarkers to diagnosis and treatment in a clinical setting.
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Affiliation(s)
- Krithika Srikanthan
- 1. Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Andrew Feyh
- 1. Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Haresh Visweshwar
- 1. Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Joseph I. Shapiro
- 1. Department of Internal Medicine, Joan C. Edwards School of Medicine, Marshall University, USA
| | - Komal Sodhi
- 2. Department of Surgery and Pharmacology, Joan C. Edwards School of Medicine, Marshall University, USA
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Jahan-Mihan A, Rodriguez J, Christie C, Sadeghi M, Zerbe T. The Role of Maternal Dietary Proteins in Development of Metabolic Syndrome in Offspring. Nutrients 2015; 7:9185-217. [PMID: 26561832 PMCID: PMC4663588 DOI: 10.3390/nu7115460] [Citation(s) in RCA: 62] [Impact Index Per Article: 6.2] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Track Full Text] [Download PDF] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/31/2015] [Revised: 10/16/2015] [Accepted: 10/28/2015] [Indexed: 12/22/2022] Open
Abstract
The prevalence of metabolic syndrome and obesity has been increasing. Pre-natal environment has been suggested as a factor influencing the risk of metabolic syndrome in adulthood. Both observational and experimental studies showed that maternal diet is a major modifier of the development of regulatory systems in the offspring in utero and post-natally. Both protein content and source in maternal diet influence pre- and early post-natal development. High and low protein dams’ diets have detrimental effect on body weight, blood pressure191 and metabolic and intake regulatory systems in the offspring. Moreover, the role of the source of protein in a nutritionally adequate maternal diet in programming of food intake regulatory system, body weight, glucose metabolism and blood pressure in offspring is studied. However, underlying mechanisms are still elusive. The purpose of this review is to examine the current literature related to the role of proteins in maternal diets in development of characteristics of the metabolic syndrome in offspring.
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Affiliation(s)
- Alireza Jahan-Mihan
- Department of Nutrition and Dietetics, Brook College of Health, University of North Florida, UNF Dr. Bldg 39, Room 3057A, Jacksonville, FL 32224, USA.
| | - Judith Rodriguez
- Department of Nutrition and Dietetics, Brook College of Health, University of North Florida, UNF Dr. Bldg 39, Room 3057A, Jacksonville, FL 32224, USA.
| | - Catherine Christie
- Department of Nutrition and Dietetics, Brook College of Health, University of North Florida, UNF Dr. Bldg 39, Room 3057A, Jacksonville, FL 32224, USA.
| | - Marjan Sadeghi
- Department of Nutrition and Dietetics, Brook College of Health, University of North Florida, UNF Dr. Bldg 39, Room 3057A, Jacksonville, FL 32224, USA.
| | - Tara Zerbe
- Department of Nutrition and Dietetics, Brook College of Health, University of North Florida, UNF Dr. Bldg 39, Room 3057A, Jacksonville, FL 32224, USA.
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Jensen KB, Forcada Y, Church DB, Niessen SJM. Evaluation and diagnostic potential of serum ghrelin in feline hypersomatotropism and diabetes mellitus. J Vet Intern Med 2015; 29:14-20. [PMID: 25619512 PMCID: PMC4858111 DOI: 10.1111/jvim.12536] [Citation(s) in RCA: 6] [Impact Index Per Article: 0.6] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 01/13/2014] [Revised: 10/28/2014] [Accepted: 12/02/2014] [Indexed: 01/06/2023] Open
Abstract
Background Ghrelin is a growth hormone secretagogue. It is a potent regulator of energy homeostasis. Ghrelin concentration is down‐regulated in humans with hypersomatotropism (HS) and increases after successful treatment. Additionally, ghrelin secretion seems impaired in human diabetes mellitus (DM). Hypothesis Serum ghrelin concentration is down‐regulated in cats with HS‐induced DM (HSDM) compared to healthy control cats or cats with DM unrelated to HS and increases after radiotherapy. Animals Cats with DM (n = 20) and with HSDM (n = 32), 13 of which underwent radiotherapy (RT‐group); age‐matched controls (n = 20). Methods Retrospective cross‐sectional study. Analytical performance of a serum total ghrelin ELISA was assessed and validated for use in cats. Differences in serum ghrelin, fructosamine, IGF‐1 and insulin were evaluated. Results Ghrelin was significantly higher (P < .001) in control cats (mean ± SD: 12.9 ± 6.8 ng/mL) compared to HSDM‐ (7.9 ± 3.3 ng/mL) and DM‐cats (6.7 ± 2.3 ng/mL), although not different between the HSDM‐ and DM‐cats. After RT ghrelin increased significantly (P = .003) in HSDM‐cats undergoing RT (from 6.6 ± 1.9 ng/mL to 9.0 ± 2.2 ng/mL) and the after RT ghrelin concentrations of HSDM cats were no longer significantly different from the serum ghrelin concentration of control cats. Serum IGF‐1 did not significantly change in HSDM‐cats after RT, despite significant decreases in fructosamine and insulin dose. Conclusion and Clinical Importance Ghrelin appears suppressed in cats with DM and HSDM, although increases after RT in HSDM, suggesting possible presence of a direct or indirect negative feedback system between growth hormone and ghrelin. Serum ghrelin might therefore represent a marker of treatment effect.
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Affiliation(s)
- K B Jensen
- Department of Clinical Sciences and Services, The Royal Veterinary College, University of London, Hatfield, Hertfordshire, UK
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Virdis A, Duranti E, Colucci R, Ippolito C, Tirotta E, Lorenzini G, Bernardini N, Blandizzi C, Taddei S. Ghrelin restores nitric oxide availability in resistance circulation of essential hypertensive patients: role of NAD(P)H oxidase. Eur Heart J 2015. [PMID: 26224075 DOI: 10.1093/eurheartj/ehv365] [Citation(s) in RCA: 11] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/13/2022] Open
Abstract
AIMS We assessed whether acute intra-arterial infusion of exogenous ghrelin can improve endothelial dysfunction by restoring nitric oxide (NO) availability in the forearm microcirculation of essential hypertensive patients. The effect of ghrelin on endothelial dysfunction (pressurized myograph), vascular oxidative stress generation (fluorescent dihydroethidium), and phosphorylation of p47phox (western blot), an index of NAD(P)H oxidase activation, in isolated small arteries taken from essential hypertensive patients (subcutaneous biopsy) were also investigated. METHODS AND RESULTS In 18 normotensive control subjects and 18 essential hypertensive patients, we studied the forearm blood flow (strain-gauge plethysmography) response to intra-arterial acetylcholine, repeated under NO synthase inhibitor N(G)-monomethyl-l-arginine (l-NMMA) or the antioxidant ascorbic acid. The protocol was repeated at the end of exogenous ghrelin intra-arterial infusion. In hypertensive patients, ghrelin normalized the blunted response to acetylcholine, restored the inhibiting effect of l-NMMA and abrogated the potentiating effect of ascorbic acid on acetylcholine. In controls, ghrelin failed to modify these vascular responses. In hypertensive patients, ghrelin decreased venous levels of malondialdehyde, lipoperoxide, and interleukin-6, and concomitantly increased endogenous antioxidant capacity. Small vessels from hypertensive patients showed an enhanced intravascular oxidative stress, which was strongly and similarly decreased by incubation with ghrelin, the NAD(P)H oxidase inhibitor gp91 ds-tat, or both. Ghrelin also normalized the overexpression of p47 phosphorylation and restored the NO availability in small vessels from hypertensive patients. CONCLUSIONS Exogenous ghrelin increases endothelial dysfunction by restoring NO availability in the forearm microcirculation of essential hypertensive patients, an effect ascribable to an antioxidant effect via inhibition of NAD(P)H oxidase activation.
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Affiliation(s)
- Agostino Virdis
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Emiliano Duranti
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Rocchina Colucci
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Chiara Ippolito
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Erika Tirotta
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Gianni Lorenzini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Nunzia Bernardini
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Corrado Blandizzi
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
| | - Stefano Taddei
- Department of Clinical and Experimental Medicine, University of Pisa, Pisa, Italy
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Comparing the Effectiveness of Total Gastrectomy and Gastric Bypass on Glucose Metabolism in Diabetic Rats. Obes Surg 2015; 26:119-25. [DOI: 10.1007/s11695-015-1730-7] [Citation(s) in RCA: 9] [Impact Index Per Article: 0.9] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 12/14/2022]
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Antunes LDC, Jornada MND, Elkfury JL, Foletto KC, Bertoluci MC. Fasting ghrelin but not PYY(3-36) is associated with insulin-resistance independently of body weight in Wistar rats. ACTA ACUST UNITED AC 2015; 58:377-81. [PMID: 24936732 DOI: 10.1590/0004-2730000002927] [Citation(s) in RCA: 1] [Impact Index Per Article: 0.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 08/12/2013] [Accepted: 01/24/2014] [Indexed: 08/30/2023]
Abstract
OBJECTIVE The objective of this study was to evaluate the association between insulin-resistance and fasting levels of ghrelin and PYY in Wistar rats. MATERIALS AND METHODS A total of 25 male Wistar rats, weighing 200-300 g, was included in this study. The animals were maintained in cages with a 12/12h light-dark cycle and fed standard chow and water ad libitum. After 12-h overnight fasting, ghrelin, PYY, insulin and glucose values were determined. Insulin resistance was assessed by means of the HOMA-IR, which was ranked and the median was used as a cut-off value to categorize insulin-resistance. HOMA-IR values equal and above 2.62 were considered insulin-resistant (IR) while values below 2.62 were considered insulin sensitive (IS). Differences between means were determined using the Student t-test. Multiple regression and Pearson's correlation test were used to evaluate the association between variables. RESULTS HOMA-IR median IQ range values for IS and IR groups were, respectively, 1.56 (0.89 - 2.16) vs. [4.06 (3.50 - 4.61); p < 0.001]. The IR group presented increased levels of fasting ghrelin, PYY and insulin respectively: [50.35 (25.99 - 74.71) pg/mL vs. 12.33 (8.77 - 15.89) pg/mL; p = 0.001]; [54.38 (37.50 - 71.26) pg/mL vs. 33.17 (22.34 - 43.99) pg/mL; p = 0.016]; [18.04 (14.48 - 21.60) uU/mL vs. 7.09 (4.83 - 9.35) uU/mL; p = 0.001]. Ghrelin, but not PYY, correlated linearly and positively with HOMA-IR: ghrelin vs. HOMA-IR (r = 0.52; p = 0.008), and PYY vs. HOMA-IR (r = 0.22; p = 0.200). This correlation was independent of body weight. CONCLUSION Fasting ghrelin and PYY serum levels are increased in lean, relatively insulin resistant Wistar rats, and this increase is independent of weight.
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Affiliation(s)
| | | | | | - Kelly Carraro Foletto
- Faculdade de Medicina, Universidade Federal do Rio Grande do Sul, Porto Alegre, RS, Brazil
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Pena-Bello L, Pertega-Diaz S, Outeiriño-Blanco E, Garcia-Buela J, Tovar S, Sangiao-Alvarellos S, Dieguez C, Cordido F. Effect of oral glucose administration on rebound growth hormone release in normal and obese women: the role of adiposity, insulin sensitivity and ghrelin. PLoS One 2015; 10:e0121087. [PMID: 25782001 PMCID: PMC4363632 DOI: 10.1371/journal.pone.0121087] [Citation(s) in RCA: 15] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Subscribe] [Scholar Register] [Received: 12/17/2014] [Accepted: 01/30/2015] [Indexed: 12/17/2022] Open
Abstract
Context Metabolic substrates and nutritional status play a major role in growth hormone (GH) secretion. Uncovering the mechanisms involved in GH secretion following oral glucose (OG) administration in normal and obese patients is a pending issue. Objective The aim of this study was to investigate GH after OG in relation with adiposity, insulin secretion and action, and ghrelin secretion in obese and healthy women, to further elucidate the mechanism of GH secretion after OG and the altered GH secretion in obesity. Participants and Methods We included 64 healthy and obese women. After an overnight fast, 75 g of OG were administered; GH, glucose, insulin and ghrelin were obtained during 300 minutes. Insulin secretion and action indices and the area under the curve (AUC) were calculated for GH, glucose, insulin and ghrelin. Univariate and multivariate linear regression analyses were employed. Results The AUC of GH (μg/L•min) was lower in obese (249.8±41.8) than in healthy women (490.4±74.6), P=0.001. The AUC of total ghrelin (pg/mL•min) was lower in obese (240995.5±11094.2) than in healthy women (340797.5±37757.5), P=0.042. There were significant correlations between GH secretion and the different adiposity, insulin secretion and action, and ghrelin secretion indices. After multivariate analysis only ghrelin AUC remained a significant predictor for fasting and peak GH.
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Affiliation(s)
- Lara Pena-Bello
- Department of Medicine, Faculty of Health Sciences, University of A Coruña, A Coruña, Spain
- Instituto de Investigación Biomedica (INIBIC), University Hospital A Coruña, A Coruña, Spain
| | - Sonia Pertega-Diaz
- Clinical Epidemiology and Biostatistics Unit, University Hospital A Coruña, A Coruña, Spain
| | | | - Jesus Garcia-Buela
- Instituto de Investigación Biomedica (INIBIC), University Hospital A Coruña, A Coruña, Spain
| | - Sulay Tovar
- Department of Physiology (CIMUS), School of Medicine-Instituto de Investigaciones Sanitarias (IDIS), Universidad de Santiago de Compostela, Santiago de Compostela, Spain, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
| | - Susana Sangiao-Alvarellos
- Department of Medicine, Faculty of Health Sciences, University of A Coruña, A Coruña, Spain
- Instituto de Investigación Biomedica (INIBIC), University Hospital A Coruña, A Coruña, Spain
| | - Carlos Dieguez
- Department of Physiology (CIMUS), School of Medicine-Instituto de Investigaciones Sanitarias (IDIS), Universidad de Santiago de Compostela, Santiago de Compostela, Spain, and CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), Santiago de Compostela, Spain
| | - Fernando Cordido
- Department of Medicine, Faculty of Health Sciences, University of A Coruña, A Coruña, Spain
- Instituto de Investigación Biomedica (INIBIC), University Hospital A Coruña, A Coruña, Spain
- Department of Endocrinology, University Hospital A Coruña, A Coruña, Spain
- * E-mail:
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King JA, Garnham JO, Jackson AP, Kelly BM, Xenophontos S, Nimmo MA. Appetite-regulatory hormone responses on the day following a prolonged bout of moderate-intensity exercise. Physiol Behav 2015; 141:23-31. [DOI: 10.1016/j.physbeh.2014.12.050] [Citation(s) in RCA: 14] [Impact Index Per Article: 1.4] [Reference Citation Analysis] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/28/2014] [Revised: 12/23/2014] [Accepted: 12/31/2014] [Indexed: 12/25/2022]
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Van Name M, Giannini C, Santoro N, Jastreboff A, Kubat J, Li F, Kursawe R, Savoye M, Duran E, Dziura J, Sinha R, Sherwin R, Cline G, Caprio S. Blunted suppression of acyl-ghrelin in response to fructose ingestion in obese adolescents: the role of insulin resistance. Obesity (Silver Spring) 2015; 23:653-61. [PMID: 25645909 PMCID: PMC4548801 DOI: 10.1002/oby.21019] [Citation(s) in RCA: 21] [Impact Index Per Article: 2.1] [Reference Citation Analysis] [Abstract] [Key Words] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 09/02/2014] [Accepted: 12/10/2014] [Indexed: 01/31/2023]
Abstract
OBJECTIVE Fructose consumption has risen alongside obesity and diabetes. Gut hormones involved in hunger and satiety (ghrelin and PYY) may respond differently to fructose compared with glucose ingestion. This study evaluated the effects of glucose and fructose ingestion on ghrelin and PYY in lean and obese adolescents with differing insulin sensitivity. METHODS Adolescents were divided into lean (n = 14), obese insulin sensitive (n = 12) (OIS), and obese insulin resistant (n = 15) (OIR). In a double-blind, cross-over design, subjects drank 75 g of glucose or fructose in random order, serum was obtained every 10 minutes for 60 minutes. RESULTS Baseline acyl-ghrelin was highest in lean and lowest in OIR (P = 0.02). After glucose ingestion, acyl-ghrelin decreased similarly in lean and OIS but was lower in OIR (vs. lean, P = 0.03). Suppression differences were more pronounced after fructose (lean vs. OIS, P = 0.008, lean vs. OIR, P < 0.001). OIS became significantly hungrier after fructose (P = 0.015). PYY was not significantly different at baseline, varied minimally after glucose, and rose after fructose. CONCLUSIONS Compared with lean, OIS adolescents have impaired acyl-ghrelin responses to fructose but not glucose, whereas OIR adolescents have blunted responses to both. Diminished suppression of acyl-ghrelin in childhood obesity, particularly if accompanied by insulin resistance, may promote hunger and overeating.
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Affiliation(s)
- Michelle Van Name
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Cosimo Giannini
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Nicola Santoro
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Ania Jastreboff
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
- Department of Internal Medicine, Division of Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Jessica Kubat
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Fangyong Li
- Yale School of Public Health, 464 Congress Street, Yale University, New Haven, CT 06519
| | - Romy Kursawe
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Mary Savoye
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Elvira Duran
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - James Dziura
- Yale School of Public Health, 464 Congress Street, Yale University, New Haven, CT 06519
| | - Rajita Sinha
- Department of Psychiatry Yale University School of Medicine, Yale Stress Center, 2 Church Street South, Suite 209, New Haven, CT 06519
- Child Study Center, Yale University School of Medicine, New Haven, CT 06520
| | - Robert Sherwin
- Department of Internal Medicine, Division of Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Gary Cline
- Department of Internal Medicine, Division of Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
| | - Sonia Caprio
- Department of Pediatrics, Division of Pediatric Endocrinology, 333 Cedar Street, Yale University School of Medicine, New Haven, CT 06520
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Wellman MK, Patterson ZR, MacKay H, Darling JE, Mani BK, Zigman JM, Hougland JL, Abizaid A. Novel Regulator of Acylated Ghrelin, CF801, Reduces Weight Gain, Rebound Feeding after a Fast, and Adiposity in Mice. Front Endocrinol (Lausanne) 2015; 6:144. [PMID: 26441834 PMCID: PMC4585333 DOI: 10.3389/fendo.2015.00144] [Citation(s) in RCA: 8] [Impact Index Per Article: 0.8] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 06/19/2015] [Accepted: 09/01/2015] [Indexed: 01/04/2023] Open
Abstract
Ghrelin is a 28 amino acid hormonal peptide that is intimately related to the regulation of food intake and body weight. Once secreted, ghrelin binds to the growth hormone secretagogue receptor-1a, the only known receptor for ghrelin and is capable of activating a number of signaling cascades, ultimately resulting in an increase in food intake and adiposity. Because ghrelin has been linked to overeating and the development of obesity, a number of pharmacological interventions have been generated in order to interfere with either the activation of ghrelin or interrupting ghrelin signaling as a means to reducing appetite and decrease weight gain. Here, we present a novel peptide, CF801, capable of reducing circulating acylated ghrelin levels and subsequent body weight gain and adiposity. To this end, we show that IP administration of CF801 is sufficient to reduce circulating plasma acylated ghrelin levels. Acutely, intraperitoneal injections of CF801 resulted in decreased rebound feeding after an overnight fast. When delivered chronically, they decreased weight gain and adiposity without affecting caloric intake. CF801, however, did cause a change in diet preference, decreasing preference for a high-fat diet and increasing preference for regular chow diet. Given the complexity of ghrelin receptor function, we propose that CF801, along with other compounds that regulate ghrelin secretion, may prove to be a beneficial tool in the study of the ghrelin system, and potential targets for ghrelin-based obesity treatments without altering the function of ghrelin receptors.
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Affiliation(s)
| | | | - Harry MacKay
- Department of Neuroscience, Carleton University, Ottawa, ON, Canada
| | | | - Bharath K. Mani
- Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Internal Medicine, Division of Endocrinology and Metabolism, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | - Jeffrey M. Zigman
- Department of Internal Medicine, Division of Hypothalamic Research, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Internal Medicine, Division of Endocrinology and Metabolism, The University of Texas Southwestern Medical Center, Dallas, TX, USA
- Department of Psychiatry, The University of Texas Southwestern Medical Center, Dallas, TX, USA
| | | | - Alfonso Abizaid
- Department of Neuroscience, Carleton University, Ottawa, ON, Canada
- *Correspondence: Alfonso Abizaid, Department of Neuroscience, Carleton University, 1125 Colonel By Drive, 329 Life Science Research Building, Ottawa, ON K1S 5B6, Canada,
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Iwakura H, Kangawa K, Nakao K. The regulation of circulating ghrelin - with recent updates from cell-based assays. Endocr J 2015; 62:107-22. [PMID: 25273611 DOI: 10.1507/endocrj.ej14-0419] [Citation(s) in RCA: 24] [Impact Index Per Article: 2.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 11/23/2022] Open
Abstract
Ghrelin is a stomach-derived orexigenic hormone with a wide range of physiological functions. Elucidation of the regulation of the circulating ghrelin level would lead to a better understanding of appetite control in body energy homeostasis. Earlier studies revealed that circulating ghrelin levels are under the control of both acute and chronic energy status: at the acute scale, ghrelin levels are increased by fasting and decreased by feeding, whereas at the chronic scale, they are high in obese subjects and low in lean subjects. Subsequent studies revealed that nutrients, hormones, or neural activities can influence circulating ghrelin levels in vivo. Recently developed in vitro assay systems for ghrelin secretion can assess whether and how individual factors affect ghrelin secretion from cells. In this review, on the basis of numerous human, animal, and cell-based studies, we summarize current knowledge on the regulation of circulating ghrelin levels and enumerate the factors that influence ghrelin levels.
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Affiliation(s)
- Hiroshi Iwakura
- Medical Innovation Center, Kyoto University Graduate School of Medicine, Kyoto 606-8507, Japan
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Fasting and meal-suppressed ghrelin levels before and after intragastric balloons and balloon-induced weight loss. Obes Surg 2014; 24:85-94. [PMID: 23918282 DOI: 10.1007/s11695-013-1053-5] [Citation(s) in RCA: 37] [Impact Index Per Article: 3.4] [Reference Citation Analysis] [Abstract] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Indexed: 02/07/2023]
Abstract
BACKGROUND Intragastric balloons may be an option for obese patients with weight loss failure. Its mode of action remains enigmatic. We hypothesised depressed fasting ghrelin concentrations and enhanced meal suppression of ghrelin secretion by the gastric fundus through balloon contact and balloon-induced delayed gastric emptying. METHODS Patients were randomised to a 13-week period of sham or balloon treatment, followed by a 13-week period of balloon treatment in everyone. Blood samples for ghrelin measurement were taken in the fasting state and every 15 min for 1 h after a breakfast meal at the start, after 13 weeks and after 26 weeks. Patients filled out scales to assess satiety and kept a food diary. RESULTS Forty obese patients (BMI 43.1 kg/m(2)) participated. At the start, fasting ghrelin values were low with a blunted ghrelin response to a test meal. The presence of a balloon had no influence on fasting or meal-suppressed ghrelin concentrations. Despite a weight loss of 10 % after 13 weeks and 15 % after 26 weeks, fasting ghrelin concentrations did not change; neither did the ghrelin response to a meal. No relation was found between ghrelin and insulin, satiety, intermeal interval, the number of meals or subsequent energy intake. Ghrelin concentrations were more suppressed with greater weight loss or with balloons located in the fundus. CONCLUSIONS Ghrelin concentrations did not change by balloon treatment after 13 and 26 weeks and, unexpectedly, did not rise despite substantial weight loss and negative energy balance. This suppression might be of benefit in the maintenance of weight loss but could not be ascribed to the balloon treatment.
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Prodam F, Monzani A, Ricotti R, Marolda A, Bellone S, Aimaretti G, Roccio M, Bona G. Systematic review of ghrelin response to food intake in pediatric age, from neonates to adolescents. J Clin Endocrinol Metab 2014; 99:1556-68. [PMID: 24601727 DOI: 10.1210/jc.2013-4010] [Citation(s) in RCA: 17] [Impact Index Per Article: 1.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/28/2023]
Abstract
OBJECTIVE Food intake and energy balance are regulated during the lifespan with critical changes in each specific period (infancy, adulthood, aging). Some of ghrelin's changes may contribute to the regulation of food intake and weight in children. We aimed to analyze the ghrelin response to feeding in lean or obese subjects from birth to adolescence. METHODS We searched PubMed, Scopus, Google Scholar, Cochrane, and EMBASE (December 1999 to February 2013) and identified 62 relevant articles, of which 29 were suitable to be included. RESULTS AND CONCLUSIONS Total ghrelin response to meals is particular, with refractoriness in neonates and lean children and an inhibition that starts from puberty. Total ghrelin levels are decreased after meals, irrespective of pubertal stages in obese children and adolescents. Conversely, total ghrelin is decreased after an oral glucose tolerance test in all ages, with the exception of neonates. Data on unacylated ghrelin response are scant but resemble those of total ghrelin. The acylated ghrelin response to meals or oral glucose tolerance test is discordant, although a precocious inhibition followed by a rise back is present in both lean and obese children. The post-feeding profile in children with Prader-Willi syndrome is also peculiar, with a conserved and deeper inhibition of all ghrelin forms.
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Affiliation(s)
- Flavia Prodam
- Division of Pediatrics, Department of Health Sciences (F.P., A.M., R.R., A.M., S.B., M.R., G.B.); Endocrinology, Department of Translational Medicine (F.P., G.A.); and Interdisciplinary Center for Obesity Study (F.P., S.B., G.B.), Università del Piemonte Orientale "A. Avogadro," Novara, 28100, Italy
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Appetite sensations, appetite signaling proteins, and glucose in obese adolescents with subclinical binge eating disorder. ISRN OBESITY 2014; 2014:312826. [PMID: 25006530 PMCID: PMC3967462 DOI: 10.1155/2014/312826] [Citation(s) in RCA: 5] [Impact Index Per Article: 0.5] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Subscribe] [Scholar Register] [Received: 12/19/2013] [Accepted: 02/05/2014] [Indexed: 12/04/2022]
Abstract
Objective. This study aimed to investigate potential differences in appetite sensations, ghrelin, peptide YY, and glucose and their relationship with energy and macronutrient intake in obese adolescents with subclinical binge eating disorder. Methods. Fifteen obese adolescents (six and nine individuals with and without subclinical binge eating disorder, resp.) qualified for this study. Visual analog scales and Three-Factor Eating Questionnaires were used to assess eating behaviours. Circulating ghrelin, peptide YY, and glucose were measured after fasting and at multiple time points postprandially following a standardized breakfast meal. Energy and macronutrient intake were measured with an ad libitum lunch buffet. Results. Emotional eating scores were significantly higher in obese adolescents with subclinical binge eating disorder. Hunger levels rose and satiety levels fell significantly over the course of the monitoring period but there was no difference between the two groups. Obese adolescents with subclinical binge eating disorder did not have significantly different levels of appetite signaling proteins or glucose. Obese adolescents with subclinical binge eating disorder had a nonsignificantly higher energy and macronutrient intake. Conclusions. A significant difference between the two groups in terms of their emotional eating scores highlights the important role that psychological factors play in relation to eating behaviours.
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Gastric and intestinal satiation in obese and normal weight healthy people. Physiol Behav 2014; 129:265-71. [PMID: 24582673 DOI: 10.1016/j.physbeh.2014.02.043] [Citation(s) in RCA: 71] [Impact Index Per Article: 6.5] [Reference Citation Analysis] [Abstract] [Key Words] [Journal Information] [Subscribe] [Scholar Register] [Received: 10/03/2013] [Revised: 01/17/2014] [Accepted: 02/18/2014] [Indexed: 02/08/2023]
Abstract
OBJECTIVE The gastrointestinal tract plays a key role in feelings of satiation. It is known that there is a reciprocal interaction between the stomach and intestine, but it is not known which factors are of gastric origin and which are intestinal. This three-step study therefore sought to provide illumination on satiation parameters with respect to body mass. METHOD In the first part, the time needed to reach maximal satiation and total caloric intake was calculated after participants (20 normal weight, 20 obese) imbibed a standardized nutrient drink. In the second part gastric emptying of solids and liquids was evaluated using the (13)C-breath test (participants: 16 normal weight, 9 obese for gastric emptying of solids; 15 normal weight, 14 obese for gastric emptying of liquids). And in the third part, fasting and post-prandial plasma glucagon-like peptide-1 (GLP-1), peptide tyrosine tyrosine (PYY) and ghrelin levels were measured after a standardized nutrient drink (participants: 20 normal weight, 20 obese). RESULTS Our results show that, when compared to those of normal weight, obese participants reached maximal satiation sooner (P=0.006), their total intake of calories was higher (P=0.013), and their gastric emptying rates were delayed (P<0.001). Furthermore, their post-prandial increase in plasma GLP-1 and PYY was reduced, (P<0.001 for both), as was their ghrelin suppression (P=0.001). DISCUSSION We conclude that, in obese subjects gastric emptying can be impaired with delayed interaction of nutrients with the intestine resulting in decreased GLP-1 and PYY secretion. This could imply that obese participants would require more calories before their maximal satiation is reached and they stop eating.
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Hage MP, El-Hajj Fuleihan G. Bone and mineral metabolism in patients undergoing Roux-en-Y gastric bypass. Osteoporos Int 2014; 25:423-39. [PMID: 24008401 DOI: 10.1007/s00198-013-2480-9] [Citation(s) in RCA: 59] [Impact Index Per Article: 5.4] [Reference Citation Analysis] [Abstract] [MESH Headings] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 03/04/2013] [Accepted: 07/29/2013] [Indexed: 01/06/2023]
Abstract
UNLABELLED Despite effective weight reduction, the impact of bariatric surgery on bone is a major concern. Mechanisms include decreased mechanical loading, calcium and vitamin D malabsorption, deficiency in other nutrients, and alterations in fat- and gut-derived hormones. The evidence to support clinical care pathways to prevent bone loss and fractures is at this point weak. INTRODUCTION There is a growing concern regarding the potential deleterious impact of bariatric surgery on bone metabolism. This comprehensive review addresses this controversial topic. METHODS We reviewed and analyzed articles evaluating bone metabolism and mechanisms for the ensuing putative bone loss in adult patients exclusively undergoing Roux-en-Y gastric bypass (RYGB) surgery, for the period spanning 1942 till September 2012. RESULTS Mechanisms identified to contribute to alterations in bone metabolism after bypass surgery include: decreased mechanical loading, calcium and vitamin D malabsorption with secondary hyperparathyroidism, deficiency in other nutrients, in addition to alterations in adipokines, gonadal steroids, and gut-derived hormones favoring bone loss, with the exception of serotonin and glucagon-like peptide-1. The relative contribution of each of these hormones to changes in bone homeostasis after bypass surgery remains undefined. Bone loss reflected by a decline in bone mineral density (BMD) and an increase in bone turnover markers have been reported in many studies, limited for the most part by the exclusive use of dual energy X-ray absorptiometry. Well-designed long-term prospective trials with fractures as an outcome, and studies investigating the magnitude, reversibility, and impact of the observed metabolic changes on fracture outcomes are lacking. CONCLUSION Robust conclusions regarding bone loss and fracture outcome after RYGB surgery cannot be drawn at this time. Although not evidence based, baseline evaluation and sequential monitoring with measurement of BMD and calciotropic hormones seem appropriate, with adequate calcium and vitamin D replacement. Beneficial interventions remain unclear.
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Affiliation(s)
- M P Hage
- Department of Internal Medicine, Division of Endocrinology, Calcium Metabolism and Osteoporosis Program, WHO Collaborating Center for Metabolic Bone Disorders, American University of Beirut-Medical Center, PO BOX: 11-0236, Riad El Solh, 1107 2020, Beirut, Lebanon
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Nass R, Farhy LS, Liu J, Pezzoli SS, Johnson ML, Gaylinn BD, Thorner MO. Age-dependent decline in acyl-ghrelin concentrations and reduced association of acyl-ghrelin and growth hormone in healthy older adults. J Clin Endocrinol Metab 2014; 99:602-8. [PMID: 24285677 PMCID: PMC3913814 DOI: 10.1210/jc.2013-3158] [Citation(s) in RCA: 39] [Impact Index Per Article: 3.5] [Reference Citation Analysis] [Abstract] [MESH Headings] [Grants] [Track Full Text] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Indexed: 01/05/2023]
Abstract
BACKGROUND Acyl-ghrelin is thought to have both orexigenic effects and to stimulate GH release. A possible cause of the anorexia of aging is an age-dependent decrease in circulating acyl-ghrelin levels. OBJECTIVES The purpose of the study was to compare acyl-ghrelin and GH concentrations between healthy old and young adults and to examine the relationship of acyl-ghrelin and GH secretion in both age groups. METHODS Six healthy older adults (age 62-74 y, body mass index range 20.9-29 kg/m(2)) and eight healthy young men (aged 18-28 y, body mass index range 20.6-26.2 kg/m(2)) had frequent blood samples drawn for hormone measurements every 10 minutes for 24 hours. Ghrelin was measured in an in-house, two-site sandwich ELISA specific for full-length acyl-ghrelin. GH was measured in a sensitive assay (Immulite 2000), and GH peaks were determined by deconvolution analysis. The acyl-ghrelin/GH association was estimated from correlations between amplitudes of individual GH secretory events and the average acyl-ghrelin concentration in the 60-minute interval preceding each GH burst. RESULTS Twenty-four-hour mean (±SEM) GH (0.48 ± 0.14 vs 2.2 ± 0.3 μg/L, P < .005) and acyl-ghrelin (14.7 ± 2.3 vs 27.8 ± 3.9 pg/mL, P < .05) levels were significantly lower in older adults compared with young adults. Twenty-four-hour cortisol concentrations were higher in the old than the young adults (15.1 ± 1.0 vs 10.6 ± 0.9 μg/dL, respectively, P < .01). The ghrelin/GH association was more than 3-fold lower in the older group compared with the young adults (0.16 ± 0.12 vs 0.69 ± 0.04, P < .001). CONCLUSIONS These results provide further evidence of an age-dependent decline in circulating acyl-ghrelin levels, which might play a role both in the decline of GH and in the anorexia of aging. Our data also suggest that with normal aging, endogenous acyl-ghrelin levels are less tightly linked to GH regulation.
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Buss J, Havel PJ, Epel E, Lin J, Blackburn E, Daubenmier J. Associations of ghrelin with eating behaviors, stress, metabolic factors, and telomere length among overweight and obese women: preliminary evidence of attenuated ghrelin effects in obesity? Appetite 2014; 76:84-94. [PMID: 24462487 DOI: 10.1016/j.appet.2014.01.011] [Citation(s) in RCA: 35] [Impact Index Per Article: 3.2] [Reference Citation Analysis] [Abstract] [Key Words] [Track Full Text] [Journal Information] [Subscribe] [Scholar Register] [Received: 07/15/2013] [Revised: 12/24/2013] [Accepted: 01/11/2014] [Indexed: 12/19/2022]
Abstract
Ghrelin regulates homeostatic food intake, hedonic eating, and is a mediator in the stress response. In addition, ghrelin has metabolic, cardiovascular, and anti-aging effects. This cross-sectional study examined associations between total plasma ghrelin, caloric intake based on 3day diet diaries, hedonic eating attitudes, stress-related and metabolic factors, and leukocyte telomere length in overweight (n=25) and obese women (n=22). We hypothesized associations between total plasma ghrelin and eating behaviors, stress, metabolic, cardiovascular, and cell aging factors among overweight women, but not among obese women due to lower circulating ghrelin levels and/or central resistance to ghrelin. Confirming previous studies demonstrating lowered plasma ghrelin in obesity, ghrelin levels were lower in the obese compared with overweight women. Among the overweight, ghrelin was positively correlated with caloric intake, giving in to cravings for highly palatable foods, and a flatter diurnal cortisol slope across 3days. These relationships were non-significant among the obese group. Among overweight women, ghrelin was negatively correlated with insulin resistance, systolic blood pressure, and heart rate, and positively correlated with telomere length. Among the obese subjects, plasma ghrelin concentrations were negatively correlated with insulin resistance, but were not significantly correlated with blood pressure, heart rate or telomere length. Total plasma ghrelin and its associations with food intake, hedonic eating, and stress are decreased in obesity, providing evidence consistent with the theory that central resistance to ghrelin develops in obesity and ghrelin's function in appetite regulation may have evolved to prevent starvation in food scarcity rather than cope with modern food excess. Furthermore, ghrelin is associated with metabolic and cardiovascular health, and may have anti-aging effects, but these effects may be attenuated in obesity.
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Affiliation(s)
- Julia Buss
- University of California, San Francisco, School of Nursing, United States
| | - Peter J Havel
- University of California, Davis, Department of Molecular Biosciences, School of Veterinary Medicine, United States; University of California, Davis, Department of Nutrition, United States
| | - Elissa Epel
- University of California, San Francisco, Department of Psychiatry, United States
| | - Jue Lin
- University of California, San Francisco, Department of Biochemistry and Biophysics, United States
| | - Elizabeth Blackburn
- University of California, San Francisco, Department of Biochemistry and Biophysics, United States
| | - Jennifer Daubenmier
- University of California, San Francisco, Osher Center for Integrative Medicine, Department of Medicine, United States.
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Abu-Farha M, Dehbi M, Noronha F, Tiss A, Alarouj M, Behbehani K, Bennakhi A, Elkum N. Gender differences in ghrelin association with cardiometabolic risk factors in arab population. Int J Endocrinol 2014; 2014:730472. [PMID: 25276131 PMCID: PMC4172923 DOI: 10.1155/2014/730472] [Citation(s) in RCA: 12] [Impact Index Per Article: 1.1] [Reference Citation Analysis] [Abstract] [Track Full Text] [Download PDF] [Figures] [Journal Information] [Submit a Manuscript] [Subscribe] [Scholar Register] [Received: 07/07/2014] [Accepted: 08/26/2014] [Indexed: 12/30/2022] Open
Abstract
Ghrelin is a stomach produced hormone that has been shown to have protective role against development of CVD which is a leading cause of death in the Arab world. The objective of this study is to examine the gender difference in association between traditional CVD risk factors and plasma ghrelin among Arabs. 359 Arab residents in Kuwait participated in a cross-sectional survey (≥20 years old): 191 were females and 168 were males. Plasma level of ghrelin was assessed using Luminex-based assay. Ghrelin levels were significantly higher in females (935 ± 78 pg/mL) than males (763 ± 65 pg/mL) (P = 0.0007). Females showed inverse association with WC (r = -0.23, P = 0.001) and HbA1C (r = -0.19, P = 0.0102) as well as SBP (r = -0.15, P = 0.0383) and DBP (r = -0.16, P = 0.0230), respectively. Higher levels of ghrelin were shown to associate with increased insulin resistance, as measured by HOMAIR, in male Arab subjects (P-trend = 0.0202) but not in females. In this study we show that higher ghrelin level was negatively associated with measures of obesity, HbA1C, and blood pressure in females and positively associated with increased insulin resistance in Arab males.
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Affiliation(s)
- Mohamed Abu-Farha
- Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, P.O. Box 1180, Kuwait City, Kuwait
| | - Mohammed Dehbi
- Diabetes Research Center, Qatar Biomedical Research Institute, P.O. Box 5825, Doha, Qatar
| | - Fiona Noronha
- Biostatistics and Epidemiology Department, Dasman Diabetes Institute, P.O. Box 1180, Kuwait City, Kuwait
| | - Ali Tiss
- Biochemistry and Molecular Biology Unit, Dasman Diabetes Institute, P.O. Box 1180, Kuwait City, Kuwait
| | - Monira Alarouj
- Dasman Diabetes Institute, P.O. Box 1180, Kuwait City, Kuwait
| | - Kazem Behbehani
- Dasman Diabetes Institute, P.O. Box 1180, Kuwait City, Kuwait
| | | | - Naser Elkum
- Biostatistics and Epidemiology Department, Dasman Diabetes Institute, P.O. Box 1180, Kuwait City, Kuwait
- Clinical Epidemiology, Sidra Medical and Research Center, P.O. Box 26999, Doha, Qatar
- *Naser Elkum:
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