RESUMO
INTRODUCTION: Single-nucleotide polymorphism (SNP) rs9939609 in the FTO gene has been associated with dietary intake and appetite traits, mainly in participants with obesity; however, it remains widely unexplored in normal weight participants. Thus, the aims of this study were (1) to compare the changes in subjective appetite sensations, ghrelin, and insulin concentrations according to the SNP rs9939609 T>A in FTO and (2) to compare dietary intake between rs9939609 genotype groups in normal weight young participants. METHODS: We conducted a quasi-experimental study involving 88 normal weight participants to analyze subjective perception of appetite, hormonal response for hunger and satiety, and dietary intake according to the rs9939609 SNP. Participants received a standardized single breakfast. Visual analogue scales (VAS) were utilized for assessing the subjective perception of appetite at fasting and immediately after breakfast and at 30, 60, 90, and 120 min postprandially. Glucose, lipid profile, ghrelin, and insulin were measured at fasting and at 120 min after breakfast. Dietary intake was assessed with a 3-day food record. The SNP was determined by allelic discrimination with TaqMan probes. To compare dietetic, biochemical, and the subjective appetite sensations, Student t test, ANCOVA test, and the repeated measures ANOVA were used. The linear regression model and the linear mixed model were used for the association analysis. Pearson correlation was used to test the correlation between two quantitative variables. RESULTS: A total of 88 people participated, 81.8% were female, with a mean body mass index of 21.8 ± 2.0 kg/m2 and a mean age of 20.6 ± 2.0. Genotype frequencies of the rs9939609 SNP were 52% for the TT allele and 48% for the TA/AA. The subjective perception of appetite named hunger, fullness, satiety, desire to eat, and prospective food consumption were similar between genotypes of the rs9939609. Participants with the TA/AA genotype showed a higher intake of added sugar (p = 0.039) than TT participants. No differences were found in ghrelin, insulin, glucose, or lipid parameters between genotypes. CONCLUSION: Carriers of the A allele from FTO gene SNP rs9939609 may have an increased preference for foods, specifically for added sugars.
Assuntos
Grelina , Insulina , Humanos , Feminino , Adulto Jovem , Adolescente , Adulto , Masculino , Grelina/genética , Genótipo , Glucose , Lipídeos , Açúcares , Dioxigenase FTO Dependente de alfa-Cetoglutarato/genéticaRESUMO
OBJECTIVE: Functional constipation is the most common form of constipation, and its exact aetiology is still unclear. However, it is known that deficiencies in hormonal factors cause constipation by changing physiological mechanisms. Motilin, ghrelin, serotonin acetylcholine, nitric oxide, and vasoactive intestinal polypeptide are factors that play a role in colon motility. There are a limited number of studies in the literature where hormone levels and gene polymorphisms of serotonin and motilin are examined. Our study aimed to investigate the role of motilin, ghrelin, and serotonin gene/receptor/transporter polymorphisms in constipation pathogenesis in patients diagnosed with functional constipation according to the Rome 4 criteria. METHODS: Sociodemographic data, symptom duration, accompanying findings, the presence of constipation in the family, Rome 4 criteria, and clinical findings according to Bristol scale of 200 cases (100 constipated patients and 100 healthy control) who applied to Istanbul Haseki Training and Research Hospital, Pediatric Gastroenterology Outpatient Clinic, between March and September 2019 (6-month period) were recorded. Polymorphisms of motilin-MLN (rs2281820), serotonin receptor-HTR3A (rs1062613), serotonin transporter-5-HTT (rs1042173), ghrelin-GHRL (rs27647), and ghrelin receptor-GHSR (rs572169) were detected by real-time PCR. RESULTS: There was no difference between the two groups in terms of sociodemographic characteristics. Notably, 40% of the constipated group had a family history of constipation. The number of patients who started to have constipation under 24 months was 78, and the number of patients who started to have constipation after 24 months was 22. There was no significant difference between constipation and control groups in terms of genotype and allele frequencies in MLN, HTR3A, 5-HTT, GHRL, and GHSR polymorphisms (p<0.05). Considering only the constipated group, the rates of gene polymorphism were similar among those with/without a positive family history of constipation, constipation onset age, those with/without fissures, those with/without skin tag, and those with type 1/type 2 stool types according to the Bristol stool scale. CONCLUSION: Our study results showed that gene polymorphisms of these three hormones may not be related to constipation in children.
Assuntos
Grelina , Motilina , Criança , Humanos , Motilina/genética , Grelina/genética , Serotonina , Constipação Intestinal/genética , Polimorfismo GenéticoRESUMO
Appetite regulation has been recognized as a promising target for the prevention of obesity, which has become a worldwide health issue. Polymorphisms in the genes of hormones or receptors including Leu72Met for ghrelin and Gln223Arg for the leptin receptor could play a role in dietary intake, hunger, and satiety process. The aim of this study was to analyze subjective appetite assessments, dietary intake, and appetite hormones in relationship to these polymorphisms. Subjects (n = 132) with normal BMIs were enrolled. Dietary intake was analyzed with 3-day diet records. Subjective appetite was measured by visual analogue scales. Biochemical parameters were measured after 12 h of fasting and 120' following ingestion of a test meal. Ghrelin and leptin levels were measured by ELISA assay (enzyme-linked immunosorbent assay) and insulin by chemiluminescence assay. The polymorphisms were determined by allelic discrimination using TaqMan® probes. Fasting ghrelin levels differed significantly between men and women. The consumption of fruit and bread/starch with added sugar servings, as indicated by dietary records, and measured ghrelin levels were higher in carriers of Leu72Met/Met72Met compared to Leu72Leu carriers; total sugar intake was higher in Gln223Gln carriers than in Gln223Arg/Arg223Arg carriers. In conclusion, the Leu72Met and Gln223Arg polymorphism in ghrelin and LEPR may contribute to differential responses to a standardized meal as evidenced by higher postprandial levels of ghrelin and may also contribute to a higher dietary sugar intake.
Assuntos
Apetite , Grelina , Fome , Receptores para Leptina , Apetite/fisiologia , Ingestão de Alimentos/genética , Feminino , Grelina/genética , Humanos , Fome/fisiologia , Masculino , Receptores para Leptina/genética , Saciação , AçúcaresRESUMO
Ghrelin is a peptide hormone mainly secreted from gastrointestinal tract that acts via the growth hormone secretagogue receptor (GHSR), which is highly expressed in the brain. Strikingly, the accessibility of ghrelin to the brain seems to be limited and restricted to few brain areas. Previous studies in mice have shown that ghrelin can access the brain via the blood-cerebrospinal fluid (CSF) barrier, an interface constituted by the choroid plexus and the hypothalamic tanycytes. Here, we performed a variety of in vivo and in vitro studies to test the hypothesis that the transport of ghrelin across the blood-CSF barrier occurs in a GHSR-dependent manner. In vivo, we found that the uptake of systemically administered fluorescent ghrelin in the choroid plexus epithelial (CPE) cells and in hypothalamic tanycytes depends on the presence of GHSR. Also, we detected lower levels of CSF ghrelin after a systemic ghrelin injection in GHSR-deficient mice, as compared to WT mice. In vitro, the internalization of fluorescent ghrelin was reduced in explants of choroid plexus from GHSR-deficient mice, and unaffected in primary cultures of hypothalamic tanycytes derived from GHSR-deficient mice. Finally, we found that the GHSR mRNA is detected in a pool of CPE cells, but is nearly undetectable in hypothalamic tanycytes with current approaches. Thus, our results suggest that circulating ghrelin crosses the blood-CSF barrier mainly by a mechanism that involves the GHSR, and also possibly via a GHSR-independent mechanism.
Assuntos
Barreira Hematoencefálica/metabolismo , Grelina/sangue , Grelina/líquido cefalorraquidiano , Receptores de Grelina/metabolismo , Animais , Células Cultivadas , Plexo Corióideo/metabolismo , Células Ependimogliais/citologia , Células Ependimogliais/metabolismo , Grelina/genética , Camundongos , Cultura Primária de Células , Transdução de SinaisRESUMO
PURPOSE: The rs17782313 variant of the MC4R gene plays an important role in the obesity phenotype. Studies that evaluate environmental factors and genetic variants associated with obesity may represent a great advance in understanding the development of this disease. This work seeks to assess the association of the polymorphism of MC4R rs17782313 on plasma parameters, including leptin, ghrelin, tumor necrosis factor (TNFα) and interleukin 6 (IL6), and on the eating behaviors of morbidly obese women. METHODS: 70 adult women with BMI between 40 and 60 kg/m2 were recruited. Laboratory and anthropometric data were recorded. Using a visual analog scale (VAS), the feelings of hunger and satiety were evaluated. The presence or absence of binge eating was evaluated through the Binge Eating Scale (BES) questionnaire. Habitual food intake was analyzed using 3-day dietary records. TaqMan® assays were conducted using real-time PCR to assess genotype polymorphism variants from peripheral blood DNA. RESULTS: This study found that female patients with the MC4R rs17782313 polymorphism had high levels of ghrelin and reduced levels of IL6 in the postprandial period. We observed a higher prevalence of severe binge eating in more than 50% of women with at least one risk allele. CONCLUSION: Our hypothesis is that the MC4R rs17782313 polymorphism may influence the release of ghrelin, even without being associated with feelings of hunger and satiety. More than half of women with this polymorphism exhibited severe binge eating. LEVEL OF EVIDENCE: Level III: case-control analytic study.
Assuntos
Leptina , Obesidade Mórbida , Adulto , Índice de Massa Corporal , Ingestão de Alimentos/genética , Comportamento Alimentar , Feminino , Grelina/genética , Humanos , Interleucina-6/genética , Leptina/genética , Obesidade Mórbida/genética , Polimorfismo de Nucleotídeo Único , Receptor Tipo 4 de Melanocortina/genética , Fator de Necrose Tumoral alfaRESUMO
BACKGROUND: Type 2 diabetes mellitus (T2D) is the most frequent type of diabetes. It has a multifactorial etiology, affecting millions of people worldwide. Ghrelin gene (GHRL) encodes the ghrelin peptide, which promotes food intake, induces body weight and adipogenesis. Several single nucleotide polymorphisms (SNPs) in GHRL gene have been associated with metabolic diseases. A protective effect of the Leu72Met (rs696217) polymorphism has been described for T2D in some populations, but this effect seems to depend on the ethnicity of the patients studied. METHODS: The aim of this study was to investigate the association between the GHRL Leu72Met (rs696217) SNP with the development of T2D and serum ghrelin levels in a Western Mexican population. We performed a case-control study in which we included 284 subjects (159 with previous T2D diagnosis and 125 control subjects (CS)). Leu72Met SNP was genotyped by using PCR-RFLPs technique. Serum ghrelin levels were measured using a commercial enzyme immunoassay. Genotypic and allelic distributions were compared using Chi square test. Student T-test and Mann-Whitney U test were used to compare quantitative variables. Odds ratio (OR) was used to evaluate the association between alleles or genotypes and T2D. Multiple and logistic regression models were performed for adjustment. A two-tailed p-value ≤0.05 was considered statistically significant. RESULTS: Leu72Leu genotype was more frequent among T2D compared to CS (p < 0.05). After adjusting for age and body composition, there was a significant protective effect of the 72Met allele for T2D development (OR 0.40 IC 95% 0.23-0.70; p ≤ 0.001). Fasting serum ghrelin levels were lower in T2D than CS (p ≤ 0.0001) irrespective of age, body weight and BMI. No associations were found between genotypes and ghrelin serum levels in our population. CONCLUSIONS: The GHRL 72Met allele decreases susceptibility for T2D development in a Western Mexican population. Serum ghrelin levels are lower in T2D independently of Leu72Met polymorphism genotype.
Assuntos
Biomarcadores/análise , Diabetes Mellitus Tipo 2/prevenção & controle , Predisposição Genética para Doença , Grelina/genética , Polimorfismo de Nucleotídeo Único , Adulto , Estudos de Casos e Controles , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Seguimentos , Genótipo , Humanos , Masculino , México/epidemiologia , Pessoa de Meia-Idade , PrognósticoRESUMO
Two performance studies were conducted to investigate the effects of 3 different sources of Cu on production parameters of piglets. A total of 256 piglets weaned at 24 ± 2 d were randomly allocated into 4 treatments with 10 or 8 replicates per treatment of 4 or 3 piglets per pen in Exp. 1 and 2, respectively. The experimental period was divided into 3 feeding phases: Phase 1 (24 to 35 d), Phase 2 (36 to 49 d), and Phase 3 (50 to 70 d). Treatments included a Control group (fed 10 mg/kg of Cu from CuSO4), a group fed 160 mg/kg of either CuSO4 (CuSO4-160) or tri-basic copper chloride (TBCC), and a group fed Cu methionine hydroxy analogue chelated (Cu-MHAC) at 150, 80, and 50 mg/kg in Phases 1, 2, and 3, respectively. The methionine value of Cu-MHAC was accounted during diet formulation to achieve the same levels of methionine across treatments. Phases 1 and 2 diets contained 2,200 and 1,500 ppm of ZnO, respectively; and antibiotics were used as growth promoters. Performance parameters were analyzed as completely randomized block design, in which each experiment was considered as a block. In trial 2, blood serum and mucosal samples, from the fundic region of the stomach, were collected from 1 piglet per replicate at day 70 and tested for serum growth hormone levels (GH) and ghrelin mRNA expression, respectively. The contrast between Cu-MHAC vs. CuSO4-160 + TBCC showed that piglets fed Cu-MHAC exhibited better feed conversion ratio (FCR) in all feeding phases compared with feeding inorganic Cu (P < 0.05). Overall, feeding Cu-MHAC improved body weight (BW), BW gain, feed intake (FI), and FCR vs. Control diet fed piglets; yet, it improved BW and FCR vs. TBCC fed piglets, and improved BW, BW gain, and FI vs. CuSO4-160 fed piglets (P < 0.05). Feeding TBCC promoted similar performance than feeding CuSO4-160, regardless of age (P > 0.05). Both ghrelin expression and growth hormone serum levels were significantly increased by feeding Cu-MHAC vs. Control diet fed animals (P < 0.01). Feeding CuSO4-160 upregulated ghrelin expression vs. Control (P < 0.01) while GH serum levels and ghrelin expression did no change by feeding TBCC compared with Control diet fed animals (P > 0.05). It was concluded that feeding Cu-MHAC at the levels tested herein can improve growth performance of piglets beyond feeding 160 ppm of either CuSO4 or TBCC, which may be partially explained by the increased expression of ghrelin and GH serum levels.
Assuntos
Ração Animal/análise , Cobre/administração & dosagem , Suplementos Nutricionais/análise , Grelina/genética , Hormônio do Crescimento/sangue , Suínos/fisiologia , Animais , Peso Corporal/efeitos dos fármacos , Dieta/veterinária , Feminino , Masculino , Metionina/análogos & derivados , Metionina/química , RNA Mensageiro/genética , Distribuição Aleatória , Estômago/fisiologia , Suínos/genética , Suínos/crescimento & desenvolvimento , Desmame , Aumento de Peso/efeitos dos fármacosRESUMO
BACKGROUND: Mechanisms of type 2 diabetes remission (T2Dr) after Roux-en-Y gastric bypass (RYGB) in obese patients appear to involve gastrointestinal hormones. OBJECTIVE: The objective of this study is to explore changes in ghrelin plasma levels and ghrelin gastrointestinal gene expression (GHRL) after RYGB, and their relationships to T2Dr. SETTING: In 20 obese women with T2D, before and 3 months after RYGB, we assessed GHRL expression by microarray and quantitative RT-PCR in gastrointestinal biopsy samples and plasma levels of ghrelin. RESULTS: After RYGB, GHRL expression increased in the excluded stomach (p < 0.05) with no change in other gastrointestinal sites. There were no significant changes in ghrelin plasma levels and no correlations with T2Dr. CONCLUSIONS: After RYGB, over-expression of GHRL gene occurs only in the excluded stomach with no correlation to T2Dr.
Assuntos
Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/cirurgia , Derivação Gástrica , Mucosa Gástrica/metabolismo , Grelina/genética , Obesidade/genética , Obesidade/cirurgia , Adolescente , Adulto , Diabetes Mellitus Tipo 2/complicações , Feminino , Trato Gastrointestinal/metabolismo , Trato Gastrointestinal/patologia , Trato Gastrointestinal/cirurgia , Perfilação da Expressão Gênica , Regulação da Expressão Gênica , Grelina/sangue , Humanos , Pessoa de Meia-Idade , Obesidade/complicações , Obesidade/metabolismo , Obesidade Mórbida/genética , Obesidade Mórbida/metabolismo , Obesidade Mórbida/cirurgia , Período Pós-Operatório , Indução de Remissão , Estômago/patologia , Estômago/cirurgia , Regulação para Cima/genética , Adulto JovemRESUMO
Obesity is a metabolic disorder that has a multifactorial etiology and affects millions of people worldwide. Ghrelin, a hormone coded by the GHRL gene, plays a role in human body composition and appetite. Single nucleotide polymorphisms (SNPs) of the GHRL gene have been associated with obesity and metabolic disorders. To evaluate the association of A-604G SNP of GHRL promoter region with serum ghrelin levels and the risk of obesity in a Mexican population. Two hundred and fifty individuals were enrolled and classified as obese or control subjects (CS) according to BMI. DNA samples, anthropometric measurements and biochemical parameters were obtained from all subjects. The A-604G SNP was genotyped using PCR-RFLPs technique. Ghrelin levels were measured using a commercial enzyme immunoassay. The G/G genotype was more frequent among obese individuals (p < 0.0001) when compared to CS. The G/A genotype and A allele were associated with protection against obesity (OR 0.29, p < 0.0001; OR 0.39, p < 0.0001 respectively), the A allele remained significant after adjusting for age and gender (OR: 0.25, p < 0.0001). Serum ghrelin levels were higher in obese patients (p = 0.004) than in CS, however, significance was lost after adjustment for age (p = 0.088). The G/G genotype was associated with higher levels of serum ghrelin (p = 0.02) independently of the effect of age. The G/G genotype of the A-604G SNP in the GHRL gene is associated with altered serum ghrelin levels and obesity. The A allele was also associated with protection against obesity in this study.
Assuntos
Predisposição Genética para Doença , Grelina/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Alelos , Feminino , Grelina/sangue , Humanos , Masculino , México , Pessoa de Meia-Idade , Obesidade/sangueRESUMO
Childhood obesity is a serious public health concern condition, as excess body fat can negatively affect a child's health. Obestatin is a hormone that regulates body weight by suppressing appetite and reducing food intake; fasting obestatin level is negatively correlated with basal insulin level. This study aims to investigate the role of obestatin in insulin resistance. A total of 54 children with simple obesity and 57 healthy controls were recruited. Levels of serum insulin, fasting blood glucose, cholesterol, triglyceride, low-density lipoprotein, and high-density lipoprotein were measured. Serum obestatin level was determined using an enzyme-linked immunosorbent assay. We found that body mass index and waist-hip ratio of obese children were significantly higher, while obestatin level in the obese group was significantly lower (P < 0.001), as compared to those of controls. In addition, obese children exhibited higher levels of insulin, total cholesterol, triglyceride, and low-density lipoprotein (P < 0.05) as compared to the controls. Fasting blood glucose and high-density lipoprotein levels were similar between the two groups (P > 0.05). Leptin level in the obese group was also higher (P < 0.05) as compared to that of control group. Results showed that insulin resistance index was positively correlated with body mass index, waist-hip ratio (r = 0.41, P < 0.001; r = 0.245, P < 0.001), and triglyceride level (r = 0.25, P = 0.04). Our study demonstrated that obestatin is negatively correlated with fasting insulin and leptin levels, and positively correlated with insulin resistance in obese children.