Short sleep duration is associated with high energy and total lipid intake in obese women: a pilot study / A curta duração do sono está associada ao elevado consumo energético e de lipídios totais em mulheres com obesidade: um estudo piloto

ABSTRACT Objective To evaluate the influence of self-reported sleep duration on ghrelin secretion and nutritional indicators in obese women. Methods This is an observational study, including 36 adult women with obesity. Sleep duration was reported while completing the general questionnaire. Dietary, laboratory, anthropometric, and body composition indicators, and resting metabolic rate, were evaluated. For statistical analysis, sleep duration data were grouped into tertiles: less than six (first tertile); equal to or above six; and less than eight (second tertile); equal to or greater than eight hours of sleep per day (third tertile). The indicators were compared for the different ranges of the sleep duration. Results There was no significant difference when comparing anthropometric, laboratory, and energy expenditure indicators between sleep tertiles. However, women with shorter sleep duration (less than 6 hours per day) had a higher mean caloric intake, compared with the tertile of eight hours or more of sleep per day. For total lipid intake, the mean consumption was higher in the first tertile (up to six hours a day). Conclusion Sleeping less than six hours a day led to an increase in energy and lipid intake in obese women. However, it did not change the plasma ghrelin concentration.

RESUMO Objetivo Avaliar a influência da duração de sono autorrelatada na secreção de grelina e indicadores nutricionais na obesidade. Métodos Trata-se de um estudo observacional, incluindo 36 mulheres adultas com obesidade. A duração do sono foi relatada durante o preenchimento do questionário de dados gerais. Foram avaliados indicadores dietéticos, laboratoriais, antropométricos e de composição corporal, além da taxa metabólica de repouso. Para análise estatística, os dados de duração de sono foram agrupados em tercis, sendo menor do que seis (primeiro tercil), igual ou acima seis e menor do que oito (segundo tercil), igual ou maior do que oito horas de sono por dia (terceiro tercil). Os indicadores supracitados foram comparados entre as diferentes faixas dos tercis de duração de sono. Resultados Não houve diferença significativa ao comparar os indicadores antropométricos, laboratoriais e do gasto de energia, entre os tercis de sono. Porém, mulheres com menor tempo de duração do sono (menos de 6 horas por dia) apresentaram maior média da ingestão calórica, comparado com o tercil de oito horas ou mais de sono por dia. Para a ingestão de lipídios totais, a média de consumo foi maior no primeiro tercil (até seis horas por dia). Conclusão Dormir menos do que seis horas por dia levou ao aumento na ingestão energética e de lipídios em mulheres com obesidade, porém, não alterou a concentração de grelina plasmática.

A single session of low-volume high-intensity interval and moderate-intensity continuous exercise elicits a transient reduction in ghrelin levels, but not in post-exercise energy intake in obese men

ABSTRACT Objective: This study investigated the acute effects of high-intensity interval (HIIE) and moderate-intensity continuous (MICE) exercise on ghrelin levels in obese men. Subjects and methods: A total of 10 obese men (age 27.6 ± 1.8 years, body mass index 35.4 ± 4.5 kg/m², body fat 39.9 ± 2.1%) performed two exercise sessions in a randomized order: HIIE (10 × 1 min intervals at 90% of the maximal heart rate [HRmax] interspersed by 1 min of active recovery) and MICE (20 min at 70% of the HRmax). Ghrelin levels were assessed pre-, post- and 1h post-exercise, and energy intake was assessed 1h post-exercise through an ad libitum meal. Results: HIIE and MICE showed a trend to decrease ghrelin levels immediately post-exercise (-14.1 ± 21.6% and −9.6 ± 23.8%, respectively, p = 0.07) and decreased 1h post-exercise (-12.7 ± 31.8% and −13.8 ± 21.7%, respectively, p < 0.05). No changes were observed for post-exercise energy intake (p > 0.05). There was a positive correlation between the change in ghrelin levels and post-exercise energy intake only for HIIE (r = 0.63, p = 0.05). Conclusion: In summary, a single session of HIIE and MICE elicits a reduction on ghrelin levels without changing post-exercise energy intake in obese men.

Serum ghrelin levels in papillary thyroid carcinoma

ABSTRACT Objective Ghrelin plays a role in several processes of cancer progression, and numerous cancer types express ghrelin and its receptor. We aimed to investigate serum levels of ghrelin in patients with papillary thyroid carcinoma (PTC) and its association with the prognostic factors in PTC. Materials and methods We enrolled 54 patients with thyroid cancer (7 male, 47 female) and 24 healthy controls (6 male, 18 female) in the study. We compared demographic, anthropometric, and biochemical data, and serum ghrelin levels between the groups. Serum ghrelin levels were measured using as enzyme-linked immunosorbent assay. Results Ghrelin levels were similar between the groups, but plasma ghrelin levels were significantly higher in tumors larger than 1 cm diameter compared with papillary microcarcinomas. Serum ghrelin levels also correlated with tumor size (r = 0.499; p < 0.001). Body mass index, thyroid-stimulating hormone, and HOMA-IR levels were similar between the groups. There were no statistically significant differences regarding average age and other prognostic parameters including lymph node invasion, capsule invasion, multifocality and surgical border invasion between patients with microcarcinoma and tumors larger than 1 cm. Conclusion In our study, no significant difference in serum ghrelin levels was determined between patients with papillary thyroid cancer and healthy controls however, serum ghrelin levels were higher in tumors larger than 1 cm compared to in those with thyroid papillary microcarcinoma.

Ghrelin plasma levels, gastric ghrelin cell density and bone mineral density in women with rheumatoid arthritis

Generalized bone loss can be considered an extra-articular manifestation of rheumatoid arthritis (RA) that may lead to the occurrence of fractures, resulting in decreased quality of life and increased healthcare costs. The peptide ghrelin has demonstrated to positively affect osteoblasts in vitro and has anti-inflammatory actions, but the studies that correlate ghrelin plasma levels and RA have contradictory results. We aimed to evaluate the correlation between total ghrelin plasma levels, density of ghrelin-immunoreactive cells in the gastric mucosa, and bone mineral density (BMD) in twenty adult women with established RA with 6 months or more of symptoms (mean age of 52.70±11.40 years). Patients with RA presented higher ghrelin-immunoreactive cells density in gastric mucosa (P=0.008) compared with healthy females. There was a positive relationship between femoral neck BMD and gastric ghrelin cell density (P=0.007). However, these same patients presented a negative correlation between plasma ghrelin levels and total femoral BMD (P=0.03). The present results indicate that ghrelin may be involved in bone metabolism of patients with RA. However, the higher density of ghrelin-producing cells in the gastric mucosa of these patients does not seem to induce a corresponding elevation in the plasma levels of this peptide.

Efecto de la gastrectomía tubular vertical en los niveles de ghrelina plasmática en pacientes obesos / Plasma ghrelin levels in the late postoperative period of vertical sleeve gastrectomy

Background: Plasma ghrelin levels may decrease after vertical sleeve gastrectomy, probably due to the excision of a large portion of the gastric fundus. It is worth exploring the long term effects of this surgical procedure on ghrelin levels and their associations with changes in body weight. Aim: To assess ghrelin levels and changes in body weight, one and five years after a vertical sleeve gastrectomy. Material and Methods: Plasma ghrelin was measured prior to gastric sleeve gastrectomy, immediately after surgery and BMI was controlled at one and five years of the postoperative period in 16 and 10 obese patients, respectively. Mean baseline body mass index was 40.4 ± 6 kg/m². Results: Ghrelin decreased in 10 patients and increased in six during the long term postoperative period. At one year, mean body mass index decreased to 25.1 ± 1.6 kg/m². Changes in weight and ghrelin levels had no relationship whatsoever. At five years of follow up, body mass index had increased to 29.9 ± 2.5 kg/m², again without any association with ghrelin levels. Conclusions: Ghrelin levels may decrease or increase after vertical sleeve gastrectomy and have no association with changes in body weight.

Fasting ghrelin but not PYY(3-36) is associated with insulin-resistance independently of body weight in Wistar rats / A grelina, mas não PYY(3-36), está associada com a resistência à insulina independente do peso corporal em ratos Wistar

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. .

Objetivo: O objetivo deste estudo foi avaliar a associação entre a resistência à insulina e os níveis de grelina e PYY em jejum em ratos Wistar. Materiais e métodos: Um total de 25 ratos Wistar machos, pesando 200-300 g, foi usado neste estudo. Os animais foram mantidos em gaiolas com um ciclo de luz escuro de 12/12h e alimentados com ração padrão e água ad libitum. Depois de um jejum de 12h, os valores de grelina, PYY, insulina e glicose foram determinados. A resistência à insulina foi avaliada pelo HOMA-IR que foi ordenado e a mediana utilizada como valor de corte para categorizar a resistência à insulina. Os valores de HOMA-IR iguais ou acima de 2,62 foram considerados resistentes à insulina (RI), enquanto valores abaixo de 2,62 foram considerados sensíveis (SI). As diferenças entre as médias foram determinadas usando-se o teste t de Student. A análise de regressões múltiplas e o teste de correlação de Pearson foram usados para se avaliar a associação entre as variáveis. Resultados: A mediana e a variação IQ do HOMA-IR para os grupos RI e SI foram, respectivamente, 1,56 (0,89 – 2,16) contra [4,06 (3,50 – 4,61); p < 0,001]. O grupo RI apresentou níveis aumentados de grelina, PYY e insulina em jejum, respectivamente, [50,35 (25,99 – 74,71) pg/mL contra 12,33 (8,77 – 15,89) pg/mL; p = 0,001]; [54,38 (37,50 – 71,26) pg/mL contra 33,17 (22,34 – 43,99) pg/mL; p = 0,016]; [18,04 (14,48 – 21,60) uU/mL contra 7,09 (4,83 – 9,35) uU/mL; p = 0.001]. A grelina, mas não PYY, se correlacionou de forma linear e positiva com o HOMA-IR: a grelina contra HOMA-IR (r = 0,52; p = 0,008), e PYY contra HOMA-IR (r = 0,22; p = 0,200). Essa correlação foi independente do peso corporal. Conclusão: Os níveis séricos de jejum de grelina ...

Possible role for growth hormone in suppressing acylated ghrelin and hunger ratings during and after intermittent exercise of different intensities in obese individuals

Body weight is influenced by both food intake and energy expenditure. Acylated ghrelin enhances appetite, and its circulating level is suppressed by Growth Hormone. Data on the acylated ghrelin responses to exercise of different intensities in obese individuals are currently not available. This study examined the effects of an intermittent exercise protocol on acylated ghrelin levels and hunger ratings in obese people. Nine inactive male ran on the treadmill at 0900 with progressive intensities of 50, 60, 70, and 80% of VO[2]max for 10, 10, 5, and 2 min respectively. Blood samples were collected before the exercise at 0845 [-15 min as the resting values], after each workload [10, 23, 31, and 36 min during exercise], and at 30, 60, and 120 min thereafter. The control trial was conducted under identical conditions with the exception of exercise. Compared to the baseline, both acylated ghrelin levels and hunger ratings were suppressed at 70% of VO[2]max during exercise [17.74 vs. 9.80 pmol/L and 4.84 vs. 2.96 unit respectively] and remained significantly lower than the control trial 2 h after the cessation of exercise [13.95 vs. 20.32 pmol/L and 3.33 vs. 6.04 unit, respectively]. Growth Hormone increased during the exercise period and peaked at 80% of VO[2]max. These findings indicate that acylated ghrelin concentrations and hunger ratings are suppressed during exercise and two hours thereafter in obese individuals, and it is possible that Growth Hormone caused the suppression of acylated ghrelin

Há associação entre acyl-grelina e inflamação em pacientes em hemodiálise? / Is there association between acyl-ghrelin and inflammation in hemodialysis patients?

INTRODUÇÃO E OBJETIVOS: Pacientes com doença renal crônica (DRC) apresentam um quadro de anorexia que pode estar relacionado com o processo inflamatório crônico, característico desta população. Assim, o presente estudo teve como objetivo avaliar se há associação entre inflamação e o hormônio orexígeno, acyl-grelina, em pacientes com DRC em hemodiálise (HD). MÉTODOS: Foram estudados 36 pacientes (61,1% homens; 46,7 ± 14,9 anos; IMC 22,9 ± 3,9 kg/m²) em programa regular de HD (65,0 ± 46,8 meses em HD). Os níveis plasmáticos de acyl-grelina e dos marcadores inflamatórios (TNF-α, IL-6 e PCR) foram medidos com o uso do método imunoenzimático (ELISA, Enzyme Linked Immunosorbent Assay). Dados antropométricos foram coletados para avaliação do estado nutricional e a ingestão alimentar foi analisada por meio de recordatório alimentar de 24h de 2 dias. RESULTADOS: Os pacientes apresentaram elevados níveis de IL-6 (83 ± 10 pg/mL), TNF-α (21,06 pg/mL [20,6-40,0]) e PCR (2,7 pg/mL [1,7-3,4]) quando comparados a valores normais. Os níveis plasmáticos de acyl-grelina (18,0 pg/mL [1,3-77,7 pg/mL]) foram baixos comparados com valores de indivíduos saudáveis. Porém, pacientes com elevado IMC (> 25 kg/m²) apresentaram menores concentrações plasmáticas de acyl-grelina (13,6 [1,3-30,5] pg/mL) em relação aos pacientes com IMC < 25 kg/m² (21,7 [7,4-77,7] pg/mL (p < 0,05). Houve correlação negativa entre o IMC e acyl-grelina (r = -0,38; p = 0,02), porém, não houve correlação significativa entre acyl-grelina e os marcadores inflamatórios. CONCLUSÃO: Apesar dos pacientes em HD apresentarem baixas concentrações de acyl-grelina e uma provável resistência a este hormônio, não houve associação entre inflamação e acyl-grelina.

INTRODUCTION AND OBJECTIVES: Patients with chronic kidney disease (CKD) present anorexia, which may be related with the chronic inflammatory process. Thus the objective of this study was to evaluate if there is association between inflammation and the orexigenic hormone, acyl-ghrelin, in CKD patients undergoing hemodialysis (HD). METHODS: Thirty-six patients were studied (61.1% men, 46.7 ± 14.9 years, BMI 22.9 ± 3.9 kg/m²) in regular HD program (65.0 ± 46.8 months). Plasma levels of acyl-ghrelin and inflammatory markers TNF-α, IL-6 and CRP were measured by enzyme immunoassay (ELI-SA, Enzyme Linked Immunosorbent Assay). Anthropometric parameters were collected for assessment of nutritional status and dietary intake was assessed by food recall. RESULTS: The patients presented elevated plasma levels of IL-6 (83 ± 10 pg/mL), TNF-α (21.06 pg/mL [20.6-40.0]) and CRP (2.7 pg/mL [1.73.4]) compared to normal values. Acylghrelin plasma levels were (18.0 [1.3 to 77.7 pg/mL]) low when compared to healthy individuals. However, patients with high BMI (> 25 kg/m²) presented lower acyl-ghrelin plasma levels (13.6 [1.3 to 30.5] pg/mL) when compared to patients with BMI < 25 kg/m² (21.7 [7.4 to 77.7] pg/mL) (p < 0.05). Acylghrelin and BMI were negatively correlated (r = -0.38, p = 0.02) and there was no significant correlation between acyl-ghrelin and inflammatory markers. CONCLUSIONS: Hemodialysis patients showed low acyl-ghrelin levels and seem to present an acyl-ghrelin resistance and there was no correlation between inflammation and this orexigenic hormone.

[Effect of surgery stress and immobilization stress on ghrelin hormone level, body weight and food intake in female rats]

Animal models of stress are a good for studying the stress induced disorders. The present study investigated the effect of immobilization and surgery stress on plasma ghrelin concentration, food intake and body weight. This was an experimental study. 40 adult female rats were divided into 4 groups. Control group: no stress. In sham Group anesthetic and antibiotic drugs were administered. Surgery group rats were subjected surgery stress. Immobilization group rats were subjected to immobilization stress for 7 days. On the seventh day, blood samples were obtained directly from the animal's heart. Serum Ghrelin concentrations were measured by ELISA. The changes in body weight during 7 days were recorded. Food intake was measured daily. Surgical stress had no significant effect on serum ghrelin concentrations but immobilization stress caused a significant increase in blood levels of ghrelin. Surgery and immobilization stress had no significant effect on body weight. Immobilization stress caused a significant increase in food intake. The effect of Stress on serum ghrelin level and food intake depends on the kind of stress

Comparação dos níveis plasmáticos de grelina nos períodos pré e pós-operatório em pacientes submetidos à plicatura gástrica associada à fundoplicatura / Comparison of ghrelin plasma levels between pre and postoperative period in patients submitted to gastric plication associated with fundoplication

RACIONAL: A doença do refluxo gastroesofágico e sua recidiva podem estar relacionadas ao ganho de peso tardio após a cirurgia bariátrica, aumentando a incidência de metaplasia colunar e neoplasia. A plicatura gástrica associada à fundoplicatura pode ser empregada com o objetivo de se tratar a doença do refluxo e o sobrepeso. OBJETIVOS: Avaliar o hormônio grelina no pré e pós-operatório, bem como a perda de peso e o controle da doença do refluxo em pacientes submetidos à gastroplicatura com fundoplicatura. MÉTODOS: Foi realizada gastroplicatura com fundoplicatura videolaparoscópica em oito pacientes. Os exames endoscópicos foram realizados no pré e no pós-operatório, bem como a coleta de sangue para a dosagem do hormônio grelina. RESULTADOS: Houve melhora dos sintomas do refluxo e das alterações na mucosa em todos os pacientes. A perda de peso foi significativa. Não houve significância na redução dos níveis plasmáticos de grelina. CONCLUSÕES: Com a plicatura gástrica e fundoplicatura: 1) não houve redução significativa no hormônio grelina, apesar do relato de diminuição da fome e aumento da saciedade pelos pacientes; 2) o procedimento foi eficaz no tratamento da doença do refluxo; 3) obteve-se perda de peso significativa.

BACKGROUND: The recurrence of the gastroesophageal reflux disease may be related to later postoperative weight gain, therefore increasing the chances of developing columnar metaplasia and cancer. The gastric plication associated with fundoplication can be employed in order to be treating the two issues. AIM: To evaluate the serum ghrelin hormone in preand postoperatively as well as weight loss and control of reflux disease in patients undergoing gastroplication associated with fundoplication. METHODS: Was performed laparoscopic gastric plication with fundoplication in eight patients; endoscopic examinations were performed pre and postoperatively as well as blood collection for ghrelin hormonal dosage. RESULTS: There was control of reflux symptoms and mucosal lesions. Weight loss was significant. Since the change of the hormone ghrelin was not of great significance. CONCLUSIONS: Gastric plication associated with fundoplication was effective in treating reflux disease with surgical indication and for weight loss in obese patients. Appetite control occurs, but not due to ghrelin, because no significant decrease of its plasmatic levels was observed.

Leptina e grelina na regulação do comportamento alimentar da tartaruga Eretmochelys imbricata (Linnaeus 1766) / Leptin and ghrelin regulates the feeding behavior of the sea turtle Eretmochelys imbricata (Linnaeus, 1766)

Durante a temporada de nidação, fêmeas de tartarugas marinhas costumam reduzir ou cessar por completo a ingestão de alimentos. Este fato sugere que o armazenamento de energia e nutrientes para a reprodução ocorra durante o período que antecede a migração para os sítios reprodutivos, enquanto estes animais ainda se encontram nas áreas de alimentação. Do ponto de vista fisiológico, tartarugas em atividade reprodutiva são capazes de permanecer longos períodos em jejum. Fatores neuroendócrinos vêm sendo recentemente apontados como os mais relevantes para a manutenção da homeostase energética de todos os vertebrados; entre eles, a leptina (hormônio anorexígeno) e a grelina (peptídeo orexígeno). Com o objetivo de compreender o mecanismo de fome e saciedade nas tartarugas marinhas, investigamos os níveis séricos destes hormônios e de outros indicadores nutricionais em fêmeas de Eretmochelys imbricata desovando no litoral do Rio Grande do Norte, Brasil. Foram coletadas amostras de sangue de 41 tartarugas durante as temporadas reprodutivas de 2010/2011 e 2011/2012. Os níveis séricos de leptina diminuíram significativamente ao longo do período de nidação, de modo a explicar a busca por alimentos ao término da temporada. Ao mesmo tempo, registramos uma tendência crescente nos níveis séricos de grelina, fator este que também justifica a remigração para as áreas de alimentação no fim do período. Não foram observadas tendências lineares para alguns dos parâmetros avaliados, entre eles: hematócrito, alanina aminotransferase (ALT), aspartato aminotransferase (AST), fosfatase alcalina (FA), gama glutamil transferase (GGT), lipoproteínas de baixa densidade (LDL) e lipoproteínas de alta densidade (HDL). É possível que a maior parte dos indicadores nutricionais tenha apresentado redução gradativa devido ao estresse fisiológico decorrente da vitelogênese e de repetidas oviposições. No entanto, é valido ressaltar que o quadro de restrição calórica por tempo prolongado ...

Reproductive female sea turtles rarely have been observed foraging during the nesting season. This suggests that prior to their reproductive migration to nesting beaches, the adult females must store sufficient energy and nutrients at their foraging grounds, and must be physiologically capable of undergoing months without feeding. Leptin (an appetite-suppressing protein) and ghrelin (a hunger-stimulating peptide) affect body weight by influencing energy intake in all vertebrates. We investigated the levels of these hormones and other physiological and nutritional parameters in nesting female hawksbill sea turtles in Rio Grande do Norte State, Brazil, by collecting consecutive blood samples from 41 turtles during the 2010/2011 and 2011/2012 reproductive seasons. We found that levels of serum leptin decreased over the nesting season, which potentially relaxed appetite suppression and led females to begin foraging either during or after the post-nesting migration. Concurrently, we recorded an increasing trend in ghrelin, which stimulated appetite towards the end of the nesting season. Both findings are consistent with the prediction that post-nesting females will begin to forage, either during or just after their post-nesting migration. We observed no seasonal trend for other physiological parameters: PCV values, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (ALP), gamma glutamyl transferase (GGT) low-density lipoprotein (LDL) and high-density lipoprotein (HDL) serum levels. The observed downward trends in general serum biochemistry levels were likely due to the physiological stress of vitellogenesis and nesting in addition to limited energy resources and probable fasting

Sinalização da grelina no coração de camundongos obesos após hipernutrição durante a lactação / Ghrelin signaling in the heart of obese mice after overnutrition during lactation

A grelina é um ligante endógeno do receptor secretagogo do hormônio do crescimento (GHSR), potente estimulador da liberação do hormônio de crescimento (GH), ingestão alimentar, e adiposidade. Além disso, sua ação hormonal inclui regulação do metabolismo energético cardíaco. Entretanto, a hipernutrição no início da vida leva ao desenvolvimento da obesidade, induz hipertrofia cardíaca, compromete a função cardíaca, e gera insuficiência cardíaca na vida adulta. Avaliar proteínas chaves no processo de sinalização da grelina no remodelamento cardíaco no coração de camundongos obesos após a hipernutrição na lactação. A obesidade foi induzida por redução de ninhada e camundongos adultos (180 dias) foram divididos em: grupo hiperalimentado, GH com obesidade decorrente de hipernutrição na lactação e controle, GC. Cardiomiócitos (cmi) do ventrículo esquerdo foram analisados por microscopia de luz e estereologia, o conteúdo e fosforilação de proteínas cardíacas: receptor de grelina (hormônio do crescimento secretagogo receptor 1a, GHSR-1a), proteína quinase-B (AKT e pAKT), phosphatidil inositol 3-quinase (PI3K), proteína quinase ativada por AMP (AMPK e pAMPK), m-TOR, pmTOR, Bax, Bcl2 e actina foram analizados por western blotting. A expressão gênica do GHSR-1a foi analisada por PCR em tempo real. A respirometria de alta resolução dos cardiomiócitos foi analisada por oxígrafo OROBOROS®. Significância estatística (P< 0,05) determinada por teste t-Student não-pareado. Nossos dados demonstram que a hipernutrição na lactação induz aumento no peso corporal, iniciado aos 10 dias de idade, persistindo até os 180 dias de idade. A glicemia, peso do fígado, e da gordura visceral foram maiores no grupo GH. Além disso, o grupo GH também apresentou aumento no peso do coração e razão peso do coração/CT (comprimento da tíbia), indicando hipertrofia e remodelamento cardíaco, aumento na expressão e conteúdo de GHSR-1a no coração, associado ao maior conteúdo de PI3K e maior conteúdo...

Ghrelin, an endogenous ligand of the growth hormone secretagogue receptor (GHS-R), has been suggested to be associated to obesity, insulin secretion, cardiovascular growth and homeostasis. GHS-R has been found in most of the tissues, and among the hormone action it is included the regulation of heart energy metabolism. Therefore, hypernutrition during early life leads to obesity, induces cardiac hypertrophy, compromises myocardial function, inducing heart failure in adulthood. We examined ghrelin signaling process in cardiac remodeling in these obese adult mice. We examined key proteins of cardiomyocyte metabolism in heart left ventricle from overfed (OG) and control (CG) groups from adult mice (180 days) overfed during lactation. Obesity was induced by litter reduction. Therefore, the study was done in adult mice 180 days old (OG, obese group (n=10) and CG, control group (n=10). The cardiomyocytes (cmy) of left ventricle were analyzed by light microscopy and stereology. The content and phosphorylation of cardiac proteins: growth hormone secretagogue receptor 1a (GHSR-1a), protein kinase B (AKT and pAKT), phosphatidil inositol 3 kinase (PI3K), AMP-activated protein kinase (AMPK and pAMPK), mTOR and pmTOR, BAX, Bcl2 and actin was achieved by western blotting. GHSR-1a gene expression was analyzed to RT-PCR. We performed high-resolution respirometry of cardiomyocytes with OROBOROS® Oxygraph-2k. Statistical significance was determined by Student t-test for unpaired. P< 0.05 was considered statistical significant. Body weight, blood glucose, liver weight, and visceral fat weight were higher in OG than CG group. Obese mice had increased heart weight and heart weight/TL (tibia length) indicating cardiac remodeling and hypertrophy, increased GHSR-1a content and expression in the heart, associated to PI3K content, increased AKT content and phosphorylation (P< 0.05), decreased Bcl2 content. In contrast, AMPK and mTOR content and phosphorylation in heart were not...

A study on the short-term effect of cafeteria diet and pioglitazone on insulin resistance and serum levels of adiponectin and ghrelin

The interaction between ghrelin and adiponectin is still controversial. We investigated the effect of cafeteria diet and pioglitazone on body weight, insulin resistance, and adiponectin/ghrelin levels in an experimental study on male Wistar rats. The animals were divided into four groups of 6 rats each, and received balanced chow with saline (CHOW-O) or pioglitazone (CHOW-P), or a cafeteria diet with saline (CAFE-O) or pioglitazone (CAFE-P). The chow/cafeteria diets were administered for 35 days, and saline/pioglitazone (10 mg·kg body weight-1·day-1) was added in the last 14 days prior to euthanasia. CAFE-O animals had a higher mean final weight (372.5 ± 21.01 g) than CHOW-O (317.66 ± 25.11 g, P = 0.017) and CHOW-P (322.66 ± 28.42 g, P = 0.035) animals. Serum adiponectin levels were significantly higher in CHOW-P (55.91 ± 20.62 ng/mL) than in CHOW-O (30.52 ± 6.97 ng/mL, P = 0.014) and CAFE-O (32.54 ± 9.03 ng/mL, P = 0.027) but not in CAFE-P. Higher total serum ghrelin levels were observed in CAFE-P compared to CHOW-P animals (1.65 ± 0.69 vs 0.65 ± 0.36 ng/mL, P = 0.006). Likewise, acylated ghrelin levels were higher in CAFE-P (471.52 ± 195.09 pg/mL) than in CHOW-P (193.01 ± 87.61 pg/mL, P = 0.009) and CAFE-O (259.44 ± 86.36 pg/mL, P = 0.047) animals. In conclusion, a cafeteria diet can lead to a significant weight gain. Although CAFE-P animals exhibited higher ghrelin levels, this was probably related to food deprivation rather than to a direct pharmacological effect, possibly attenuating the increase in adiponectin levels.

Weight homeostasis & its modulators in hyperthyroidism before & after treatment with carbimazole.

Background & objectives: Hyperthyroidism is associated with increased food intake, energy expenditure and altered body composition. This study was aimed to evaluate the role of adipocytokines in weight homeostasis in patients with hyperthyroidism. Methods: Patients (n=27, 11men) with hyperthyroidism (20 Graves’ disease, 7 toxic multinodular goiter) with mean age of 31.3±4.2 yr and 28 healthy age and body mass index (BMI) matched controls were studied. They underwent assessment of lean body mass (LBM) and total body fat (TBF) by dual energy X-ray absorptiometer (DXA) and blood sample was taken in the fasting state for measurement of leptin, adiponectin, ghrelin, insulin, glucose and lipids. Patients were re-evaluated after 3 months of treatment as by that time all of them achieved euthyroid state with carbimazole therapy. Results: The LBM was higher (P<0.001) in healthy controls as compared to hyperthyroid patients even after adjustment for body weight (BW), whereas total body fat was comparable between the two groups. Serum leptin levels were higher in patients with hyperthyroidism than controls (22.3±3.7 and 4.1±0.34 ng/ml, P<0.001), whereas adiponectin levels were comparable. Plasma acylated ghrelin was higher in patients than in controls (209.8±13.3 vs 106.2±8.2 pg/ml, P<0.05). Achievement of euthyroidism was associated with significant weight gain (P<0.001) and significant increase in lean body mass (P<0.001). The total body fat also increased but insignificantly from 18.4±1.8 to 19.9±1.8 kg. There was significant decrease (P<0.05) in serum leptin and acylated ghrelin but adiponectin levels remained unaltered after treatment. Serum leptin positively correlated with TBF and this correlation persisted even after adjustment for BW, BMI, gender and age (r=0.62, P=0.001). However, serum leptin and acylated ghrelin did not correlate with the presence or absence of hyperphagia. Interpretation & conclusion: Patients with hyperthyroidism predominantly had decreased lean body mass which increased after achievement of euthyroidism with carbimazole. The hyperphagia and the alterations in weight homeostasis associated with hyperthyroidism were independent of circulating leptin and ghrelin levels.

Correlations of circulating peptide YY and ghrelin with body weight, rate of weight gain, and time required to achieve the recommended daily intake in preterm infants

The objective was to elucidate the relationships between serum concentrations of the gut hormone peptide YY (PYY) and ghrelin and growth development in infants for potential application to the clinical observation index. Serum concentrations of PYY and ghrelin were measured using radioimmunoassay from samples collected at the clinic. For each patient, gestational age, birth weight, time required to return to birth weight, rate of weight gain, time required to achieve recommended daily intake (RDI) standards, time required for full-gastric feeding, duration of hospitalization, and time of administration of total parenteral nutrition were recorded. Serum PYY and ghrelin concentrations were significantly higher in the preterm group (N = 20) than in the full-term group (N = 20; P < 0.01). Within the preterm infant group, the serum concentrations of PYY and ghrelin on postnatal day (PND) 7 (ghrelin = 1485.38 ± 409.24; PYY = 812.37 ± 153.77 ng/L) were significantly higher than on PND 1 (ghrelin = 956.85 ± 223.09; PYY = 545.27 ± 204.51 ng/L) or PND 3 (ghrelin = 1108.44 ± 351.36; PYY = 628.96 ± 235.63 ng/L; P < 0.01). Both serum PYY and ghrelin concentrations were negatively correlated with body weight, and the degree of correlation varied with age. Serum ghrelin concentration correlated negatively with birth weight and positively with the time required to achieve RDI (P < 0.05). In conclusion, serum PYY and ghrelin concentrations reflect a negative energy balance, predict postnatal growth, and enable compensation. Further studies are required to elucidate the precise concentration and roles of PYY and ghrelin in newborns and to determine the usefulness of measuring these hormones in clinical practice.

Growth hormone response to growth hormone-releasing peptide-2 in growth hormone-deficient Little mice

OBJECTIVE: To investigate a possible direct, growth hormone-releasing, hormone-independent action of a growth hormone secretagogue, GHRP-2, in pituitary somatotroph cells in the presence of inactive growth hormonereleasing hormone receptors. MATERIALS AND METHODS: The responses of serum growth hormone to acutely injected growth hormone-releasing P-2 in lit/litmice, which represent a model of GH deficiency arising frommutated growth hormone-releasing hormonereceptors, were compared to those observed in the heterozygous (lit/+) littermates and wild-type (+/+) C57BL/6J mice. RESULTS: After the administration of 10 mcg of growth hormone-releasing P-2 to lit/lit mice, a growth hormone release of 9.3±1.5 ng/ml was observed compared with 1.04±1.15 ng/ml in controls (p<0.001). In comparison, an intermediate growth hormone release of 34.5±9.7 ng/ml and a higher growth hormone release of 163±46 ng/ml were induced in the lit/+ mice and wild-type mice, respectively. Thus, GHRP-2 stimulated growth hormone in the lit/lit mice, and the release of growth hormone in vivo may be only partially dependent on growth hormone-releasing hormone. Additionally, the plasma leptin and ghrelin levels were evaluated in the lit/lit mice under basal and stimulated conditions. CONCLUSIONS: Here, we have demonstrated that lit/lit mice, which harbor a germline mutation in the Growth hormone-releasing hormone gene, maintain a limited but statistically significant growth hormone elevation after exogenous stimulation with GHRP-2. The present data probably reflect a direct, growth hormone-independent effect on Growth hormone S (ghrelin) stimulation in the remaining pituitary somatotrophs of little mice that is mediated by growth hormone S-R 1a.

La reducción del sueño como factor de riesgo para obesidad / Sleep deprivation as a risk factor for obesity

Nocturnal sleep patterns may be a contributing factor for the epidemic of obesity. Epidemiologic ana experimental studies have reported that sleep restriction is an independent risk factor for weight gain and obesity. Moreover, sleep restriction is significantly associated with incidence and prevalence of obesity and several non-transmissible chronic diseases. Experimental sleep restriction is related to altered plasma leptin and ghrelin concentrations. Both hormones are directly related to appetite and satiety mechanisms. Also, a higher activity of the orexin/hypocretin system has been reported, as well as changes in glucose metabolism and autonomic nervous system. Some studies indicate that these endocrine changes could be associated with a higher diurnal food intake and preference for energy- dense foods. All these changes could result in a positive energy balance, leading to weight gain and a higher obesity risk in the long-term. The present article summarizes the epidemiologic and experimental evidence related to sleep deprivation and higher obesity risk. The possible mechanisms are highlighted.

Correlation of ghrelin, adiponectin and leptin to BMI and treatment outcome in breast cancer patients

Body mass index [BMI] is an independent prognostic factor for survival in breast cancer patients. Patients with higher BMI were found to have poorer cancer prognosis and lower survival rates. Many factors as ghrelin, adiponectin and leptin, have been implicated in obesity but their correlation with breast carcinogenesis and treatment outcome is still a debate.To identify the relation of ghrelin, adiponectin and leptin with BMI in breast cancer patients and their possible role in carcinogenesis and treatment outcome. Sera from 80 breast cancer patients were analyzed. Ghrelin, adiponectin and leptin were assayed by commercial RIA kits, and their levels were correlated with BMI, clinicopathological parameters and relapse-free survival. The median duration of patients' follow-up was 32 months.73.7% of the cohort was overweight/obese. Compared to breast cancer patients with normal BMI, overweight/obese patients had a significantly higher tumor size and higher histological grade. Overweight/obese patients had higher leptin and lower ghrelin and adiponectin levels. Adiponectin was lower in patients with higher tumor grade and lymph node involvement, while ghrelin decreased with increasing tumor size and histological grade. Only serum ghrelin levels were significantly correlated to better disease-free survival.Ghrelin, adiponectin and leptin are significant factors in controlling BMI in breast cancer patients but only ghrelin is a significant predictor of better outcome and recurrence-free survival

[ influence of circuit resistance training intensity on ghrelin to obestatin ratio of plasma in healthy young women]

Ghrelin and obestatin are orexigenic and anorexigenic peptides, respectively, which are believed to be important in the regulation of energy homeostasis and body weight control. The purpose of this study was to clarify the possible mechanisms of resistance training in energy homeostasis and weight control. Twenty-seven female college students, age 22 +/- 1.54 yr, and body mass index 20.76 +/- 1.86 kg/m2 [mean +/- SE] were randomly assigned to the experimental and control groups. Subjects performed circuit-resistance training protocol with 40% and 80% 1 RM for 4 weeks. Circulating levels of total ghrelin, obestatin, ghrelin to obestatin ratio and glucose were measured before and after 4 weeks intervention for all subjects. One-way ANOVA revealed a higher and significant [P<0.05] post- training change in circulating levels of ghrelin to obestatin ratio as well as plasma obestatin concentrations significantly decreased [P<0.05] in the 80% IRM group. It seems that resistance training-induced energy deficit in the 80% IRM group resulted that ghrelin precursor goes to the production of ghrelin. Thus, obestatin secretion is reduced and ghrelin to obestatin ratio is increased to stimulate food intake behavior, compensating for lost energy sources and eventually restoring the body's energy balance

role of calprotectin and ghrelin in diagnosis of post ERCP pancreatitis

Acute pancreatitis is a common and dreaded complication of endoscopic retrograde cholangiopancreatography [ERCP] patients. The study identified the incidence of post ERCP pancreatitis and role of serum calprotectin and ghrelin in its diagnosis. One hundred forty two patients underwent ERCP-related procedures were studied. Serum amylase, lipase, calprotectin and ghrelin concentrations were measured 24 hours after the procedure using ELISA, kinetic and colorimetric methods. Thirty two healthy controls were enrolled. In post ERCP group, mean level of amylase was 146.03 +/- 57.40 U/L, lipase 328.37 +/- 133.95 U/L, calprotectin 3.26 +/- 2.99 U/L and gherkin 2.56 +/- 1.76 mg/l. In controls mean level of amylase was 58.13 +/- 15.96U/L, lipase 18 1.63 +/- 5 1.94 U/L, calprotectin 0.49 +/- 0.17UL and ghrelin 2.59 +/- 0.19 mg/1. A statistical significant increase was reported [p<0.001] in levels of amylase, lipase and calprotectin between the two groups without significant in ghrelin level