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1.
Allergy Asthma Proc ; 45(4): e38-e45, 2024 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-38982607

RESUMO

Background: Sleep can be affected in patients with chronic spontaneous urticaria (CSU). The mechanisms of sleep regulation remain poorly understood. Orexin-A, a neuroexcitatory peptide, plays a role in coordinating sleep-wake states. Ghrelin and leptin are involved in sleep regulation through the orexin system. Objective: The effects of orexin-A, ghrelin, and leptin on sleep quality in patients with CSU have not been investigated. We aimed to determine the effects of CSU on sleep quality and the association between serum orexin-A, ghrelin, and leptin levels, and sleep quality in patients with CSU. Methods: Thirty-three patients with CSU and 34 sex- and age-matched controls were included in the study. Serum orexin-A, leptin, and ghrelin levels, and the Pittsburgh Sleep Quality Index (PSQI) and the Epworth Sleepiness Scale (ESS) scores were measured in patients with CSU and in the controls; also used were the chronic urticaria quality-of-life questionnaire score and the urticaria activity score used for 7 consecutive days. Results: Median (minimum-maximum) orexin-A, leptin, and ghrelin levels in patients were 385 pg/mL (90-495 pg/mL), 3.1 ng/mL (0-21.2 ng/mL), and 701.8 pg/mL (101.9-827.7 pg/mL), respectively. Median serum orexin-A and leptin levels were higher in the patients compared with the controls (p < 0.001 and p = 0.012, respectively), whereas the median serum ghrelin levels were similar to the controls (p = 0.616). The serum orexin-A level was positively correlated with ghrelin (r = 0.298, p = 0.014), PSQI sleep quality (r = 0.356, p = 0.003), and ESS (r = 0.357, p = 0.003). Conclusion: Serum orexin-A is associated with sleep quality in patients with CSU. Further studies are needed to elucidate the role of ghrelin and leptin on sleep quality in patients with CSU.


Assuntos
Urticária Crônica , Grelina , Leptina , Orexinas , Qualidade de Vida , Qualidade do Sono , Humanos , Grelina/sangue , Orexinas/sangue , Leptina/sangue , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Urticária Crônica/sangue , Estudos de Casos e Controles , Inquéritos e Questionários , Adulto Jovem
2.
Sci Rep ; 14(1): 14971, 2024 06 28.
Artigo em Inglês | MEDLINE | ID: mdl-38951515

RESUMO

Fetal alcohol spectrum disorders (FASD) are a severe developmental condition resulting from exposure to alcohol during pregnancy. The aim of this study was to examine the concentrations of hormones involved in appetite regulation-ghrelin, leptin, and putative peptide YY-3 (PYY)-in the serum of individuals with FASD. Additionally, we investigated the relationship between these hormone levels and clinical indicators. We conducted an enzyme-linked immunosorbent assay on samples collected from 62 FASD patients and 23 individuals without the condition. Our results revealed a significant decrease in leptin levels among FASD patients compared to the control group (5.124 vs. 6.838 ng/mL, p = 0.002). We revealed no statistically significant differences in the levels of other hormones studied (ghrelin and PYY). Comparisons of hormone levels were also conducted in three subgroups: FAS, neurobehavioral disorders associated with prenatal alcohol exposure and FASD risk, as well as by sex. Assignment to FASD subgroups indicated changes only for leptin. Sex had no effect on the levels of hormones. Moreover, the levels of leptin showed a negative correlation with cortisol levels and a positive correlation with BMI and proopiomelanocortin. Alterations in appetite regulation can contribute to the improper development of children with FASD, which might be another factor that should be taken into consideration in the proper treatment of patients.


Assuntos
Transtornos do Espectro Alcoólico Fetal , Grelina , Leptina , Peptídeo YY , Humanos , Leptina/sangue , Transtornos do Espectro Alcoólico Fetal/sangue , Feminino , Grelina/sangue , Masculino , Peptídeo YY/sangue , Gravidez , Criança , Adulto , Estudos de Casos e Controles , Pré-Escolar
3.
Transl Psychiatry ; 14(1): 277, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965230

RESUMO

The mechanisms contributing to alcohol use disorder (AUD) are complex and the orexigenic peptide ghrelin, which enhances alcohol reward, is implied as a crucial modulator. The major proportion of circulating ghrelin is however the non-octanoylated form of ghrelin, des-acyl ghrelin (DAG), whose role in reward processes is unknown. As recent studies show that DAG decreases food intake, we hypothesize that DAG attenuates alcohol-related responses in animal models. Acute and repeated DAG treatment dose-dependently decreased alcohol drinking in male and female rats. In these alcohol-consuming male rats, repeated DAG treatment causes higher levels of dopamine metabolites in the ventral tegmental area, an area central to reward processing. The role of DAG in reward processing is further supported as DAG prevents alcohol-induced locomotor stimulation, reward in the conditioned place preference paradigm, and dopamine release in the nucleus accumbens in male rodents. On the contrary, DAG does not alter the memory of alcohol reward or affect neurotransmission in the hippocampus, an area central to memory. Further, circulating DAG levels are positively correlated with alcohol drinking in female but not male rats. Studies were conducted in attempts to identify tentative targets of DAG, which currently are unknown. Data from these recombinant cell system revealed that DAG does not bind to either of the monoamine transporters, 5HT2A, CB1, or µ-opioid receptors. Collectively, our data show that DAG attenuates alcohol-related responses in rodents, an effect opposite to that of ghrelin, and contributes towards a deeper insight into behaviors regulated by the ghrelinergic signaling pathway.


Assuntos
Consumo de Bebidas Alcoólicas , Dopamina , Grelina , Núcleo Accumbens , Recompensa , Área Tegmentar Ventral , Animais , Grelina/farmacologia , Grelina/metabolismo , Masculino , Ratos , Feminino , Dopamina/metabolismo , Área Tegmentar Ventral/metabolismo , Área Tegmentar Ventral/efeitos dos fármacos , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Etanol/farmacologia , Etanol/administração & dosagem , Humanos , Hipocampo/metabolismo , Hipocampo/efeitos dos fármacos , Ratos Sprague-Dawley
4.
Behav Brain Funct ; 20(1): 18, 2024 Jul 04.
Artigo em Inglês | MEDLINE | ID: mdl-38965529

RESUMO

BACKGROUND: Anxiety disorders are one of the most common mental disorders. Ghrelin is a critical orexigenic brain-gut peptide that regulates food intake and metabolism. Recently, the ghrelin system has attracted more attention for its crucial roles in psychiatric disorders, including depression and anxiety. However, the underlying neural mechanisms involved have not been fully investigated. METHODS: In the present study, the effect and underlying mechanism of ghrelin signaling in the nucleus accumbens (NAc) core on anxiety-like behaviors were examined in normal and acute stress rats, by using immunofluorescence, qRT-PCR, neuropharmacology, molecular manipulation and behavioral tests. RESULTS: We reported that injection of ghrelin into the NAc core caused significant anxiolytic effects. Ghrelin receptor growth hormone secretagogue receptor (GHSR) is highly localized and expressed in the NAc core neurons. Antagonism of GHSR blocked the ghrelin-induced anxiolytic effects. Moreover, molecular knockdown of GHSR induced anxiogenic effects. Furthermore, injection of ghrelin or overexpression of GHSR in the NAc core reduced acute restraint stress-induced anxiogenic effects. CONCLUSIONS: This study demonstrates that ghrelin and its receptor GHSR in the NAc core are actively involved in modulating anxiety induced by acute stress, and raises an opportunity to treat anxiety disorders by targeting ghrelin signaling system.


Assuntos
Ansiedade , Grelina , Núcleo Accumbens , Ratos Sprague-Dawley , Receptores de Grelina , Transdução de Sinais , Estresse Psicológico , Animais , Grelina/metabolismo , Núcleo Accumbens/metabolismo , Núcleo Accumbens/efeitos dos fármacos , Masculino , Ansiedade/metabolismo , Ansiedade/psicologia , Receptores de Grelina/metabolismo , Receptores de Grelina/genética , Ratos , Estresse Psicológico/metabolismo , Estresse Psicológico/psicologia , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Comportamento Animal/efeitos dos fármacos
5.
J Cell Biol ; 223(10)2024 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-38958606

RESUMO

Calorie restriction increases lifespan. Among the tissue-specific protective effects of calorie restriction, the impact on the gastrointestinal tract remains unclear. We report increased numbers of chromogranin A-positive (+), including orexigenic ghrelin+ cells, in the stomach of calorie-restricted mice. This effect was accompanied by increased Notch target Hes1 and Notch ligand Jag1 and was reversed by blocking Notch with DAPT, a gamma-secretase inhibitor. Primary cultures and genetically modified reporter mice show that increased endocrine cell abundance is due to altered Lgr5+ stem and Neurog3+ endocrine progenitor cell proliferation. Different from the intestine, calorie restriction decreased gastric Lgr5+ stem cells, while increasing a FOXO1/Neurog3+ subpopulation of endocrine progenitors in a Notch-dependent manner. Further, activation of FOXO1 was sufficient to promote endocrine cell differentiation independent of Notch. The Notch inhibitor PF-03084014 or ghrelin receptor antagonist GHRP-6 reversed the phenotypic effects of calorie restriction in mice. Tirzepatide additionally expanded ghrelin+ cells in mice. In summary, calorie restriction promotes Notch-dependent, FOXO1-regulated gastric endocrine cell differentiation.


Assuntos
Restrição Calórica , Proteína Forkhead Box O1 , Grelina , Receptores Notch , Transdução de Sinais , Animais , Grelina/metabolismo , Proteína Forkhead Box O1/metabolismo , Proteína Forkhead Box O1/genética , Receptores Notch/metabolismo , Receptores Notch/genética , Camundongos , Diferenciação Celular , Camundongos Endogâmicos C57BL , Receptores Acoplados a Proteínas G/metabolismo , Receptores Acoplados a Proteínas G/genética , Proliferação de Células , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Fatores de Transcrição Hélice-Alça-Hélice Básicos/genética , Células-Tronco/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Proteínas do Tecido Nervoso/genética , Mucosa Gástrica/metabolismo , Fatores de Transcrição HES-1/metabolismo , Fatores de Transcrição HES-1/genética , Masculino , Estômago
6.
Int J Mol Sci ; 25(11)2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38891884

RESUMO

Pro-B amino-terminal natriuretic peptide (NT-proBNP) is a diagnostic marker for heart failure (HF), a severe complication of chronic kidney disease (CKD). However, its significance in CKD is not clear, as other factors, such as renal function, may also have an impact. Recent studies have shown that ghrelin treatment is effective in HF in the general population, but the impact of ghrelin on cardiac function in CKD patients is still unknown. Our study aimed to investigate the factors associated with NT-proBNP in pre-dialysis CKD patients and to evaluate the correlation between NT-proBNP and ghrelin and acyl-ghrelin, molecules determined using ELISA methods. In a cross-sectional observational study, we included 80 patients with pre-dialysis CKD, with a mean age of 68 years and 50% men. The median values for NT-proBNP were 351.8 pg/mL, for acyl ghrelin 16.39 pg/mL, and for ghrelin 543.32 pg/mL. NT-proBNP was correlated with ghrelin (p = 0.034, r = 0.24), acyl-ghrelin (p = 0.033, r = -0.24), estimated glomerular filtration rate (p = 0.027, r = -0.25), serum urea (p = 0.006, r = 0.31), and ferritin (p = 0.041, r = 0.28). In multivariate analysis, ghrelin (p = 0.040) and blood urea (p = 0.040) remained significant predictors for NT-proBNP levels. NT-proBNP was a significant predictor for acyl-ghrelin (p = 0.036). In conclusion, in pre-dialysis CKD patients, a high value of NT-proBNP was associated with a high value of total ghrelin and a low value of acyl-ghrelin.


Assuntos
Grelina , Peptídeo Natriurético Encefálico , Fragmentos de Peptídeos , Insuficiência Renal Crônica , Humanos , Grelina/sangue , Masculino , Feminino , Peptídeo Natriurético Encefálico/sangue , Idoso , Insuficiência Renal Crônica/sangue , Insuficiência Renal Crônica/complicações , Fragmentos de Peptídeos/sangue , Pessoa de Meia-Idade , Estudos Transversais , Biomarcadores/sangue , Taxa de Filtração Glomerular , Diálise Renal , Idoso de 80 Anos ou mais
7.
Wiad Lek ; 77(4): 652-658, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38865618

RESUMO

OBJECTIVE: Aim: The aim of this research is to assess the anti-inflammatory effect of ghrelin in mice models of polymicrobial sepsis. PATIENTS AND METHODS: Materials and Methods: 35 male albino Swiss mice, ages 8-12 weeks, weighing 23-33g, were randomly separated into five groups n = 7; normal group was fed their usual diets until time of sampling, the sham group subjected to Anaesthesia and laparotomy, sepsis group subjected to cecal ligation and puncture, vehicle group was given an equivalent volume of intraperitoneal saline injections immediately after cecal ligation and puncture, and the ghrelin group was treated with 80 µg/kg of ghrelin intraperitoneal injections immediately following cecal ligation and puncture. Twenty hours after cecal ligation and puncture, mice were sacrificed; myocardial tissue and serum samples were collected. Serum IL-1ß, NF-κB, and TLR4 levels were measured, and inflammatory response's effects on cardiac tissue were evaluated. RESULTS: Results: The mean serum IL-1ß, NF-κB, and TLR4 levels were markedly elevated in the sepsis and vehicle groups than in the normal and sham groups. The mean serum levels of IL-1ß, NF-κB, and TLR4 were considerably lower in the ghrelin-treated group than in the vehicle and sepsis groups. Myocardium tissue of the normal and sham groups showed normal architecture. The sepsis and vehicle groups had a severe myocardial injury. The histological characteristics of ghrelin-treated mice differed slightly from those of the normal and sham groups. CONCLUSION: Conclusions: Our study concluded that ghrelin exerts anti-inflammatory effects in polymicrobial sepsis, as indicated by a considerable decrease in the IL-1ß, NF-κB and TLR4 serum levels.


Assuntos
Modelos Animais de Doenças , Endotoxemia , Grelina , Interleucina-1beta , NF-kappa B , Receptor 4 Toll-Like , Animais , Grelina/sangue , Camundongos , Masculino , Endotoxemia/tratamento farmacológico , Endotoxemia/sangue , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Receptor 4 Toll-Like/metabolismo , NF-kappa B/metabolismo , Inflamação/tratamento farmacológico , Sepse/tratamento farmacológico , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico
8.
J Anim Sci ; 1022024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38875129

RESUMO

We investigated the effects of a calf starter supplemented with calcium salts of medium-chain fatty acids (MCFA-Ca) on growth and plasma hormone concentration in calves. Twelve Holstein calves were randomly assigned to two dietary groups (without supplementation [CON] and supplemented with MCFA-Ca [MCFA]) from 4 d of age. Calves were fed 1.0 kg/d of milk replacer until 5 wk of age and were completely weaned at 7 wk of age. Calves in the MCFA group received a calf starter containing 1% MCFA-Ca. dry matter intake (DMI) was measured daily, and body weight was measured weekly. Rumen fluid was collected at 13 wk of age to measure pH and volatile fatty acid concentration. Preprandial blood samples were collected weekly to measure the basal plasma hormone and metabolite concentrations. At 4, 8, and 13 wk of age, peri-prandial blood samples were collected every 30 min, from 60 min before feeding to 120 min after feeding, to observe metabolic responses to feeding. In addition, insulin sensitivity was assessed using euglycemic-hyperinsulinemic clamps at 4, 8, and 13 wk of age in three calves from each treatment. There were no differences in starter and hay DMI between the treatments. However, the average daily gain (ADG) after weaning was higher in the MCFA group than in the CON group. Weekly changes in plasma parameters did not differ between the treatments. Plasma concentrations of preprandial ghrelin and postprandial total ketone bodies at 13 wk of age were higher in the MCFA group than in the CON group. At 8 wk of age, peri-prandial plasma insulin concentrations were lower in the MCFA group than in the CON group. There were no differences between the treatments in terms of insulin sensitivity. The present study suggested that feeding weaning calves MCFA-Ca increases the ADG during the postweaning period, which may be mediated by endocrine signals, such as enhanced ghrelin secretion and decreased insulin secretion, without altering insulin sensitivity.


Calves are prone to growth retardation because of insufficient energy intake during the weaning transition period. Starch is the main energy source used in the formulation of calf starters. However, there is a concern that preweaned calves do not have sufficient functional rumen and small intestine to digest large amounts of starch, causing diarrhea, and decreased feed intake. Medium-chain fatty acids are easily accessible to calves and are expected to have functional properties, such as increasing the plasma concentration of ghrelin, which may enhance growth by stimulating growth hormone. The effect of calf starter supplementation with medium-chain fatty acids on growth performance and metabolism has not been evaluated previously and was evaluated in this study. Medium-chain fatty acids were fed in the form of calcium salts as pelleted solid feed. The results showed that feeding medium-chain fatty acids increased plasma ghrelin concentration, decreased insulin concentration, suggesting that these metabolic changes might be beneficial for calf growth performance.


Assuntos
Ração Animal , Fenômenos Fisiológicos da Nutrição Animal , Dieta , Animais , Bovinos/crescimento & desenvolvimento , Bovinos/fisiologia , Bovinos/metabolismo , Ração Animal/análise , Dieta/veterinária , Masculino , Fenômenos Fisiológicos da Nutrição Animal/efeitos dos fármacos , Ácidos Graxos/metabolismo , Suplementos Nutricionais/análise , Insulina/sangue , Insulina/metabolismo , Cálcio/metabolismo , Cálcio/sangue , Distribuição Aleatória , Grelina/sangue , Grelina/metabolismo , Rúmen/metabolismo , Rúmen/efeitos dos fármacos
9.
BMC Surg ; 24(1): 176, 2024 Jun 05.
Artigo em Inglês | MEDLINE | ID: mdl-38840104

RESUMO

BACKGROUND: Laparoscopic sleeve gastrectomy combined with fundoplication (LSGFD) can significantly control body weight and achieve effective anti-reflux effects. The aim of this study is to investigate the correlation between the alteration in Ghrelin levels and weight loss following SGFD, and to compare Ghrelin levels, weight loss and metabolic improvements between SG and SGFD, with the objective of contributing to the existing body of knowledge on SGFD technique in the management of patients with obesity and gastroesophageal reflux disease (GERD). METHODS: A retrospective analysis was conducted on the clinical data of 115 obese patients who underwent bariatric surgery between March 2023 and June 2023 at the Department of Minimally Invasivew Surgery, Hernia and Abdominal Wall Surgery, People's Hospital of Xinjiang Uygur Autonomous Region. The subjects were divided into two groups based on surgical methods: sleeve gastrectomy group (SG group, 93 cases) and sleeve gastrectomy combined with fundoplication group (SGFD group, 22 cases). Clinical data, such as ghrelin levels before and after the operation, were compared between the two groups, and the correlation between changes in ghrelin levels and weight loss effectiveness after the operation was analyzed. RESULTS: Three months after the operation, there was no significant difference in body mass, BMI, EWL%, fasting blood glucose, triglyceride, cholesterol, and uric acid levels between the SG and SGFD groups (P > 0.05). However, the SGFD group exhibited a significant decrease in body weight, BMI, and uric acid levels compared to preoperative levels (P < 0.05), while the decrease in ghrelin levels was not statistically significant (P > 0.05). Logistic regression analysis indicated that ghrelin levels three months after the operation were influential in postoperative weight loss. CONCLUSION: The reduction of plasma Ghrelin level in patients after SGFD is not as obvious as that in patients after SG, but it can make obese patients get the same good weight loss and metabolic improvement as patients after SG. Ghrelin level at the third month after operation is the influencing factor of postoperative weight loss.


Assuntos
Fundoplicatura , Gastrectomia , Refluxo Gastroesofágico , Grelina , Redução de Peso , Humanos , Grelina/sangue , Redução de Peso/fisiologia , Masculino , Feminino , Gastrectomia/métodos , Estudos Retrospectivos , Adulto , Fundoplicatura/métodos , Refluxo Gastroesofágico/cirurgia , Refluxo Gastroesofágico/sangue , Refluxo Gastroesofágico/etiologia , Pessoa de Meia-Idade , Obesidade Mórbida/cirurgia , Obesidade Mórbida/sangue , Laparoscopia/métodos , Cirurgia Bariátrica/métodos , Resultado do Tratamento
10.
Front Endocrinol (Lausanne) ; 15: 1411483, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38828411

RESUMO

Ghrelin is a peptide hormone with various important physiological functions. The unique feature of ghrelin is its serine 3 acyl-modification, which is essential for ghrelin activity. The major form of ghrelin is modified with n-octanoic acid (C8:0) by ghrelin O-acyltransferase. Various acyl modifications have been reported in different species. However, the underlying mechanism by which ghrelin is modified with various fatty acids remains to be elucidated. Herein, we report the purification of bovine, porcine, and equine ghrelins. The major active form of bovine ghrelin was a 27-amino acid peptide with an n-octanoyl (C8:0) modification at Ser3. The major active form of porcine and equine ghrelin was a 28-amino acid peptide. However, porcine ghrelin was modified with n-octanol (C8:0), whereas equine ghrelin was modified with n-butanol (C4:0) at Ser3. This study indicates the existence of structural divergence in ghrelin and suggests that it is necessary to measure the minor and major forms of ghrelin to fully understand its physiology.


Assuntos
Grelina , Animais , Grelina/metabolismo , Grelina/química , Cavalos , Bovinos , Suínos , Sequência de Aminoácidos , Acilação , Caprilatos/metabolismo
11.
Nutrients ; 16(12)2024 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-38931301

RESUMO

Liver-expressed antimicrobial peptide-2 (LEAP-2) has mutual antagonism with ghrelin, which evokes food intake under a freely fed state. Nevertheless, the impact of LEAP-2 on ghrelin under time-restricted feeding (TRF), which has benefits in the context of metabolic disease, is still unknown. This study aims to explore the impact of central administration of LEAP-2 on the ingestion behavior of rats, which was evaluated using their cumulative food intake in the TRF state. Before intracerebroventricular (ICV) administration of O-n-octanoylated ghrelin (0.1 nmol/rat), as a food-stimulatory model, the rats received various doses of LEAP-2 (0.3, 1, 3 nmol/rat, ICV). Cumulative food intake was recorded at 1, 2, 4, 8, 12, and 24 h after ICV injection under 12 h freely fed and TRF states in a light phase. In 12 h freely fed and TRF states, central administration of ghrelin alone induced feeding behavior. Pre-treatment with LEAP-2 (1 and 3 nmol/rat, ICV) suppressed ghrelin-induced food intake in a dose-dependent manner in a 12 h freely fed state instead of a TRF state, which may have disturbed the balance of ghrelin and LEAP-2. This study provides neuroendocrine-based evidence that may explain why TRF sometimes fails in fighting obesity/metabolic dysfunction-associated steatotic liver disease in clinics.


Assuntos
Ingestão de Alimentos , Comportamento Alimentar , Grelina , Animais , Grelina/farmacologia , Grelina/administração & dosagem , Masculino , Ratos , Ingestão de Alimentos/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Comportamento Alimentar/efeitos dos fármacos , Injeções Intraventriculares , Peptídeos Catiônicos Antimicrobianos/administração & dosagem , Peptídeos Catiônicos Antimicrobianos/farmacologia , Ratos Sprague-Dawley , Estado de Consciência , Proteínas Sanguíneas
12.
PLoS One ; 19(5): e0292997, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38728264

RESUMO

BACKGROUND: Current research suggests that energy transfer through human milk influences infant nutritional development and initiates metabolic programming, influencing eating patterns into adulthood. To date, this research has predominantly been conducted among women in high income settings and/or among undernourished women. We will investigate the relationship between maternal body composition, metabolic hormones in human milk, and infant satiety to explore mechanisms of developmental satiety programming and implications for early infant growth and body composition in Samoans; a population at high risk and prevalence for overweight and obesity. Our aims are (1) to examine how maternal body composition influences metabolic hormone transfer from mother to infant through human milk, and (2) to examine the influences of maternal metabolic hormone transfer and infant feeding patterns on early infant growth and satiety. METHODS: We will examine temporal changes in hormone transfers to infants through human milk in a prospective longitudinal cohort of n = 80 Samoan mother-infant dyads. Data will be collected at three time points (1, 3, & 4 months postpartum). At each study visit we will collect human milk and fingerpick blood samples from breastfeeding mother-infant dyads to measure the hormones leptin, ghrelin, and adiponectin. Additionally, we will obtain body composition measurements from the dyad, observe breastfeeding behavior, conduct semi-structured interviews, and use questionnaires to document infant hunger and feeding cues and satiety responsiveness. Descriptive statistics, univariate and multivariate analyses will be conducted to address each aim. DISCUSSION: This research is designed to advance our understanding of variation in the developmental programming of satiety and implications for early infant growth and body composition. The use of a prospective longitudinal cohort alongside data collection that utilizes a mixed methods approach will allow us to capture a more accurate representation on both biological and cultural variables at play in a population at high risk of overweight and obesity.


Assuntos
Composição Corporal , Leite Humano , Humanos , Leite Humano/metabolismo , Leite Humano/química , Feminino , Lactente , Estudos Prospectivos , Estudos Longitudinais , Leptina/sangue , Leptina/metabolismo , Adiponectina/sangue , Adiponectina/metabolismo , Adulto , Grelina/sangue , Grelina/metabolismo , Desenvolvimento Infantil/fisiologia , Masculino , Aleitamento Materno , Fenômenos Fisiológicos da Nutrição do Lactente , Saciação/fisiologia , Mães
13.
Curr Oncol Rep ; 26(7): 762-772, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38771469

RESUMO

PURPOSE OF REVIEW: The following review will highlight the development of anamorelin to treat cancer anorexia-cachexia syndrome (CACS) including the potential benefits, limitations, and future directions. RECENT FINDINGS: Ghrelin, a 28-amino acid peptide hormone, is secreted by the stomach mucosa and regulates appetite, promotes lipogenesis, increases body weight, improves gastric motility, reduces catabolic wasting and inflammation. Several randomized, double-blind, placebo-controlled clinical trials evaluating anamorelin, a ghrelin agonist, for the treatment of CACS have reported improvement in appetite and body composition including both lean body and fat mass; however, most studies noted no improvement in physical function as assessed by measuring non-dominant hand-grip strength. Common adverse effects of anamorelin include the development of diabetes mellitus, hyperglycemia, and less frequently, hepatic abnormalities and cardiovascular events including conduction abnormalities, hypertension, and ischemic cardiomyopathy. Anamorelin has the potential to stimulate appetite, improve gastric movement, and may have anti-inflammatory effects on patients with CACS. In patients with cancer, studies involving anamorelin combined with other multimodal treatments including nutrition counseling (branched chain amino acids, omega 3 fatty acids, and other nutrients), exercise, treatment of hormonal abnormalities including hypogonadism and hypovitaminosis D, and anti-inflammatory agents are needed. Compliance with multimodality treatment has been a barrier and future studies may need to incorporate motivational counseling to promote adherence.


Assuntos
Anorexia , Caquexia , Neoplasias , Humanos , Caquexia/tratamento farmacológico , Caquexia/etiologia , Neoplasias/complicações , Neoplasias/tratamento farmacológico , Anorexia/tratamento farmacológico , Anorexia/etiologia , Oligopeptídeos/uso terapêutico , Glicina/uso terapêutico , Glicina/análogos & derivados , Grelina/uso terapêutico , Aminoácidos de Cadeia Ramificada/uso terapêutico , Hidrazinas
14.
Endocrinology ; 165(7)2024 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-38815068

RESUMO

The growth hormone secretagogue receptor (GHSR), primarily known as the receptor for the hunger hormone ghrelin, potently controls food intake, yet the specific Ghsr-expressing cells mediating the orexigenic effects of this receptor remain incompletely characterized. Since Ghsr is expressed in gamma-aminobutyric acid (GABA)-producing neurons, we sought to investigate whether the selective expression of Ghsr in a subset of GABA neurons is sufficient to mediate GHSR's effects on feeding. First, we crossed mice that express a tamoxifen-dependent Cre recombinase in the subset of GABA neurons that express glutamic acid decarboxylase 2 (Gad2) enzyme (Gad2-CreER mice) with reporter mice, and found that ghrelin mainly targets a subset of Gad2-expressing neurons located in the hypothalamic arcuate nucleus (ARH) and that is predominantly segregated from Agouti-related protein (AgRP)-expressing neurons. Analysis of various single-cell RNA-sequencing datasets further corroborated that the primary subset of cells coexpressing Gad2 and Ghsr in the mouse brain are non-AgRP ARH neurons. Next, we crossed Gad2-CreER mice with reactivable GHSR-deficient mice to generate mice expressing Ghsr only in Gad2-expressing neurons (Gad2-GHSR mice). We found that ghrelin treatment induced the expression of the marker of transcriptional activation c-Fos in the ARH of Gad2-GHSR mice, yet failed to induce food intake. In contrast, food deprivation-induced refeeding was higher in Gad2-GHSR mice than in GHSR-deficient mice and similar to wild-type mice, suggesting that ghrelin-independent roles of GHSR in a subset of GABA neurons is sufficient for eliciting full compensatory hyperphagia in mice.


Assuntos
Núcleo Arqueado do Hipotálamo , Privação de Alimentos , Neurônios GABAérgicos , Grelina , Glutamato Descarboxilase , Hiperfagia , Receptores de Grelina , Animais , Masculino , Camundongos , Neurônios GABAérgicos/metabolismo , Receptores de Grelina/genética , Receptores de Grelina/metabolismo , Hiperfagia/metabolismo , Grelina/metabolismo , Grelina/farmacologia , Núcleo Arqueado do Hipotálamo/metabolismo , Privação de Alimentos/fisiologia , Glutamato Descarboxilase/metabolismo , Glutamato Descarboxilase/genética , Camundongos Transgênicos , Proteína Relacionada com Agouti/metabolismo , Proteína Relacionada com Agouti/genética , Camundongos Endogâmicos C57BL
15.
Food Funct ; 15(12): 6523-6535, 2024 Jun 17.
Artigo em Inglês | MEDLINE | ID: mdl-38805370

RESUMO

Muscle damage can occur due to excessive, high-intensity, or inappropriate exercise. It is crucial for athletes and sports enthusiasts to have access to ways that expedite their recovery and alleviate discomfort. Our previous clinical trial demonstrated the anti-inflammatory and muscle damage-ameliorating properties of Lacticaseibacillus paracasei PS23 (PS23), prompting us to further explore the role of this probiotic in muscle damage recovery. This post-hoc analysis of a randomized controlled study investigated potential mediators between the intake of PS23 and the prevention of strength loss after muscle damage. We recruited 105 students from a sports university who had participated in the previously published clinical trial. These participants were randomly allocated to three groups, receiving capsuled live PS23 (L-PS23), heat-treated PS23 (HT-PS23), or a placebo over a period of six weeks. Baseline and endpoint measurements were taken for the levels of circulating ghrelin and other blood markers, stress, mood, quality of life, and the fecal microbiota. A significant increase in ghrelin levels was recorded in the L-PS23 group compared to the other groups. Additionally, both L-PS23 and HT-PS23 interventions led to positive shifts in the gut microbiota composition, particularly in elevated Lacticaseibacillus, Blautia, and Lactobacillus populations. The abundance of these bacteria was positively correlated with exercise performance and inversely correlated with inflammatory markers. In conclusion, dietary supplementation with PS23 may enhance exercise performance and influence muscle damage by increasing ghrelin levels and modulating the gut microbiota composition. Further clarification of the possible mechanisms and clinical implications is required.


Assuntos
Microbioma Gastrointestinal , Grelina , Lacticaseibacillus paracasei , Probióticos , Humanos , Grelina/sangue , Grelina/metabolismo , Masculino , Adulto Jovem , Feminino , Adulto , Fezes/microbiologia , Método Duplo-Cego
16.
Appetite ; 200: 107509, 2024 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-38795943

RESUMO

Glycomacropeptide (GMP) has a unique amino acid profile which may make less satiating than other dietary proteins. This study assessed the feasibility and likely acceptability of a leucine-enriched GMP drink and determined appetite response in older adults (OA). Thirteen OA (11f; 70 ± 4 years) were recruited for sensory assessments of a leucine-enriched GMP drink when mixed with water and with fruit smoothie, compared with whey protein isolate (WHEY). Participants also partook in a single focus group exploring acceptability to protein and supplementation. Separately, a counterbalanced, double-blind study with twelve OA (8f; 69 ± 3 years) was conducted to determine appetite and gut hormone responses. Fasting subjective appetite was recorded using visual analogue scales and a fasted venous blood sample was collected (to measures acyl-ghrelin, PYY, GLP-1, and CCK) before participants consumed either: GMP protein (27g + 3g leucine, 350 mL water), WHEY (30g, 350 mL water), or water. Participants rested for 240 min, with appetite measures and blood sampling throughout. An ad libitum pasta-based meal was then consumed. Sensory testing revealed low pleasantness rating for GMP in water vs. WHEY (16 ± 14 vs 31 ± 24, p = 0.016). GMP addition to smoothie reduced pleasantness (26 ± 21 vs. 61 ± 29, p = 0.009) and worsened the aroma (46 ± 15 vs. 69 ± 28, p = 0.014). The focus group revealed uncertainty of protein needs and a scepticism of supplements, with preference for food. Gut hormone response did not differ between GMP and WHEY (nAUC for all gut hormones p > 0.05). There was no difference between conditions for lunch ad libitum intake (549 ± 171 kcal, 512 ± 238 kcal, 460 ± 199 kcal for GMP, WHEY, and water, p = 0.175), or for subjective appetite response. Leucine-enriched GMP was not less satiating than WHEY, and low palatability and scepticism of supplements question the likely acceptability of GMP supplementation. Providing trusted nutritional advice and food enrichment/fortification may be preferred strategies for increasing protein intake in OA.


Assuntos
Apetite , Caseínas , Estudos de Viabilidade , Hormônios Gastrointestinais , Fragmentos de Peptídeos , Proteínas do Soro do Leite , Humanos , Feminino , Masculino , Apetite/efeitos dos fármacos , Idoso , Projetos Piloto , Hormônios Gastrointestinais/sangue , Método Duplo-Cego , Caseínas/administração & dosagem , Caseínas/farmacologia , Proteínas do Soro do Leite/administração & dosagem , Proteínas do Soro do Leite/farmacologia , Fragmentos de Peptídeos/sangue , Leucina/administração & dosagem , Leucina/farmacologia , Grelina/sangue , Saciação/efeitos dos fármacos , Ingestão de Alimentos , Suplementos Nutricionais , Pessoa de Meia-Idade , Peptídeo YY/sangue , Peptídeo 1 Semelhante ao Glucagon/sangue , Proteínas Alimentares/administração & dosagem
17.
Zhongguo Zhong Yao Za Zhi ; 49(10): 2699-2709, 2024 May.
Artigo em Chinês | MEDLINE | ID: mdl-38812170

RESUMO

A systematic evaluation of the differences in the chemical composition and efficacy of the different forms of Galli Gigerii Endothelium Corneum(GGEC) was conducted based on modern analytical techniques and a functional dyspepsia(FD) rat model, which clarifies the material basis of the digestive efficacy of GGEC. Proteins, enzymes, polysaccharides, amino acids, and flavonoids in GGEC powder and decoction were determined respectively. The total protein of the powder and decoction was 0.06% and 0.65%, respectively, and the pepsin and amylase potency of the powder was 27.03 and 44.05 U·mg~(-1) respectively. The polysaccharide of the decoction was 0.03%, and there was no polysaccharide detected in the powder. The total L-type amino acids in the powder and decoction were 279.81 and 8.27 mg·g~(-1) respectively, and the total flavonoid content was 59.51 µg·g~(-1). Enzymes and flavonoids were not detected in the decoction. The powder significantly reduced nutrient paste viscosity, while the decoction and control group showed no significant reduction in nutrient paste viscosity. FD rat models were prepared by iodoacetamide gavage and irregular diet. The results showed that both powder and decoction significantly increased the gastric emptying effect, small intestinal propulsion rate, digestive enzymes activity, gastrin(GAS), motilin(MTL), ghrelin(GHRL) and reduced vasoactive intestinal peptide(VIP), 3-(2-ammo-nioethyl)-5-hydroxy-1H-indolium maleate(5-HT), and somatostatin(SST) content in rats(P<0.05, P<0.01). Comparison of GGEC decoction and powder administration between groups of the same dosage level showed that gastrointestinal propulsion and serum levels of GAS, GHRL, VIP, and SST in the powder group were significantly superior to those in the decoction and that the gastrointestinal propulsion, as well as serum levels of MTL, GAS, and GHRL were slightly higher than those of the decoction with two times its raw dose, and the serum levels of SST, 5-HT, and VIP in the powder group were slightly lower than those of the decoction with two times its raw dose. In conclusion, both decoction and powder have therapeutic effects on FD, but there is a significant difference between the two effects. Under the same dosage, the digestive efficacy of the powder is significantly better than that of the decoction, and the decoction needs to increase the dosage to compensate for the efficacy. It is hypothesized that the digestive efficacy of the GGEC has a duality, and the digestive active ingredients of the powder may include enzymes and L-type amino acids, while the decoction mainly relies on L-type amino acids to exert its efficacy. This study provides new evidence to investigate the digestive active substances of the GGEC and to improve the effectiveness of the drug in the clinic.


Assuntos
Dispepsia , Ratos Sprague-Dawley , Animais , Ratos , Masculino , Dispepsia/tratamento farmacológico , Dispepsia/fisiopatologia , Dispepsia/metabolismo , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/farmacologia , Medicamentos de Ervas Chinesas/química , Humanos , Flavonoides/química , Flavonoides/farmacologia , Motilina , Peptídeo Intestinal Vasoativo/metabolismo , Grelina , Somatostatina
18.
Mol Biol Rep ; 51(1): 663, 2024 May 21.
Artigo em Inglês | MEDLINE | ID: mdl-38771494

RESUMO

BACKGROUND: Alcohol use disorder (AUD) is a relapsing disease described as excessive use of alcohol. Evidence of the role of DNA methylation in addiction is accumulating. Ghrelin is an important peptide known as appetite hormone and its role in addictive behavior has been identified. Here we aimed to determine the methylation levels of two crucial genes (GHRL and GHSR) in ghrelin signaling and further investigate the association between methylation ratios and plasma ghrelin levels. METHODS: Individuals diagnosed with (n = 71) and without (n = 82) AUD were recruited in this study. DNA methylation levels were measured through methylation-sensitive high-resolution melting (MS-HRM). Acylated ghrelin levels were detected by ELISA. The GHRL rs696217 polymorphism was analyzed by the standard PCR-RFLP method. RESULTS: GHRL was significantly hypermethylated (P < 0.0022) in AUD between 25 and 50% methylation than in control subjects but no significant changes of GHSR methylation were observed. Moreover, GHRL showed significant positive correlation of methylation ratio between 25 and 50% with age. A significant positive correlation between GHSR methylation and ghrelin levels in the AUD group was determined (P = 0.037). The level of GHRL methylation and the ghrelin levels showed a significant association in the control subjects (P = 0.042). CONCLUSION: GHSR and GHRL methylation levels did not change significantly between control and AUD groups. However, GHRL and GHSR methylations seemed to have associations with plasma ghrelin levels in two groups. This is the first study investigating the DNA methylation of GHRL and GHSR genes in AUD.


Assuntos
Alcoolismo , Metilação de DNA , Grelina , Receptores de Grelina , Humanos , Grelina/genética , Grelina/sangue , Receptores de Grelina/genética , Masculino , Metilação de DNA/genética , Feminino , Estudos de Casos e Controles , Alcoolismo/genética , Adulto , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único/genética
19.
Mol Metab ; 84: 101950, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38697291

RESUMO

OBJECTIVE: The number of individuals affected by metabolic dysfunction associated fatty liver disease [1] is on the rise, yet hormonal contributors to the condition remain incompletely described and only a single FDA-approved treatment is available. Some studies suggest that the hormones ghrelin and LEAP2, which act as agonist and antagonist/inverse agonist, respectively, for the G protein coupled receptor GHSR, may influence the development of MAFLD. For instance, ghrelin increases hepatic fat whereas synthetic GHSR antagonists do the opposite. Also, hepatic steatosis is less prominent in standard chow-fed ghrelin-KO mice but more prominent in 42% high-fat diet-fed female LEAP2-KO mice. METHODS: Here, we sought to determine the therapeutic potential of a long-acting LEAP2 analog (LA-LEAP2) to treat MAFLD in mice. LEAP2-KO and wild-type littermate mice were fed a Gubra-Amylin-NASH (GAN) diet for 10 or 40 wks, with some randomized to an additional 28 or 10 days of GAN diet, respectively, while treated with LA-LEAP2 vs Vehicle. Various metabolic parameters were followed and biochemical and histological assessments of MAFLD were made. RESULTS: Among the most notable metabolic effects, daily LA-LEAP2 administration to both LEAP2-KO and wild-type littermates during the final 4 wks of a 14 wk-long GAN diet challenge markedly reduced liver weight, hepatic triglycerides, plasma ALT, hepatic microvesicular steatosis, hepatic lobular inflammation, NASH activity scores, and prevalence of higher-grade fibrosis. These changes were accompanied by prominent reductions in body weight, without effects on food intake, and reduced plasma total cholesterol. Daily LA-LEAP2 administration during the final 10 d of a 41.5 wk-long GAN diet challenge also reduced body weight, plasma ALT, and plasma total cholesterol in LEAP2-KO and wild-type littermates and prevalence of higher grade fibrosis in LEAP2-KO mice. CONCLUSIONS: Administration of LA-LEAP2 to mice fed a MAFLD-prone diet markedly improves several facets of MAFLD, including hepatic steatosis, hepatic lobular inflammation, higher-grade hepatic fibrosis, and transaminitis. These changes are accompanied by prominent reductions in body weight and lowered plasma total cholesterol. Taken together, these data suggest that LEAP2 analogs such as LA-LEAP2 hold promise for the treatment of MAFLD and obesity.


Assuntos
Dieta Hiperlipídica , Inflamação , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica , Redução de Peso , Animais , Camundongos , Inflamação/metabolismo , Redução de Peso/efeitos dos fármacos , Feminino , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/patologia , Dieta Hiperlipídica/efeitos adversos , Camundongos Endogâmicos C57BL , Fígado/metabolismo , Fígado/patologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/tratamento farmacológico , Masculino , Grelina/metabolismo
20.
JAMA Neurol ; 81(6): 603-610, 2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38709502

RESUMO

Importance: Out-of-hospital cardiac arrest survival rates have markedly risen in the last decades, but neurological outcome only improved marginally. Despite research on more than 20 neuroprotective strategies involving patients in comas after cardiac arrest, none have demonstrated unequivocal evidence of efficacy; however, treatment with acyl-ghrelin has shown improved functional and histological brain recovery in experimental models of cardiac arrest and was safe in a wide variety of human study populations. Objective: To determine safety and potential efficacy of intravenous acyl-ghrelin to improve neurological outcome in patients in a coma after cardiac arrest. Design, Setting, and Participants: A phase 2, double-blind, placebo-controlled, multicenter, randomized clinical trial, Ghrelin Treatment of Comatose Patients After Cardiac Arrest: A Clinical Trial to Promote Cerebral Recovery (GRECO), was conducted between January 18, 2019, and October 17, 2022. Adult patients 18 years or older who were in a comatose state after cardiac arrest were assessed for eligibility; patients were from 3 intensive care units in the Netherlands. Expected death within 48 hours or unfeasibility of treatment initiation within 12 hours were exclusion criteria. Interventions: Patients were randomized to receive intravenous acyl-ghrelin, 600 µg (intervention group), or placebo (control group) within 12 hours after cardiac arrest, continued for 7 days, twice daily, in addition to standard care. Main Outcomes and Measures: Primary outcome was the score on the Cerebral Performance Categories (CPC) scale at 6 months. Safety outcomes included any serious adverse events. Secondary outcomes were mortality and neuron-specific enolase (NSE) levels on days 1 and 3. Results: A total of 783 adult patients in a coma after cardiac arrest were assessed for eligibility, and 160 patients (median [IQR] age, 68 [57-75] years; 120 male [75%]) were enrolled. A total of 81 patients (51%) were assigned to the intervention group, and 79 (49%) were assigned to the control group. The common odds ratio (OR) for any CPC improvement in the intervention group was 1.78 (95% CI, 0.98-3.22; P = .06). This was consistent over all CPC categories. Mean (SD) NSE levels on day 1 after cardiac arrest were significantly lower in the intervention group (34 [6] µg/L vs 56 [13] µg/L; P = .04) and on day 3 (28 [6] µg/L vs 52 [14] µg/L; P = .08). Serious adverse events were comparable in incidence and type between the groups. Mortality was 37% (30 of 81) in the intervention group vs 51% (40 of 79) in the control group (absolute risk reduction, 14%; 95% CI, -2% to 29%; P = .08). Conclusions and Relevance: In patients in a coma after cardiac arrest, intravenous treatment with acyl-ghrelin was safe and potentially effective to improve neurological outcome. Phase 3 trials are needed for conclusive evidence. Trial Registration: Clinicaltrialsregister.eu: EUCTR2018-000005-23-NL.


Assuntos
Coma , Grelina , Fármacos Neuroprotetores , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Grelina/uso terapêutico , Método Duplo-Cego , Idoso , Coma/etiologia , Fármacos Neuroprotetores/uso terapêutico , Neuroproteção/fisiologia , Parada Cardíaca/complicações , Parada Cardíaca Extra-Hospitalar/complicações
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