Leptin plays a role in the multiplication of and inflammation in ovarian granulosa cells in polycystic ovary syndrome through the JAK1/STAT3 pathway.

OBJECTIVES: The authors determined the level of Expression of Leptin (LEP) in Polycystic Ovary Syndrome (PCOS) patients with or without obesity and in GCs treated with insulin. METHODS: LEP expression was first assessed in ovary cortex specimens collected from women with PCOS with or without obesity as well as from healthy controls. Ovarian Granulosa Cells (OGCs) induced by insulin extracted from a mouse model were used in further functional research. RESULTS: Real-time PCR and western blotting indicated that LEP expression was upregulated in GCs induced by insulin, in comparison with that in GCs not induced by insulin. Furthermore, the knockdown of LEP resulted in a reduction in growth and multiplication and an increase in apoptosis and inflammation in GCs induced by insulin. Next, the authors evaluated the effect of LEP on three key pathways of inflammation (MAPK, NF-kB, and JAK1/STAT3); results showed that the JAK1/STAT3 pathway was induced by LEP knockdown, as evidenced by the upregulation of phosphor-JAK1, phosphor-STAT3, and nuclear STAT3 expression. Administration of curcumin, a specific inhibitor of STAT3, counteracted the effect of LEP knockdown on cell inflammation and apoptosis. CONCLUSION: The present data suggest that upregulation of LEP expression in the PCOS granulosa cell model is essential for reducing apoptosis and inflammation by modulating the JAK1/STAT3 pathway axis.

Leptin impairs the therapeutic effect of ionizing radiation in oral squamous cell carcinoma cells.

PURPOSE: Leptin, an important hormone controlling energy homeostasis, has been linked to the pathogenesis of oral squamous cell carcinoma (OSCC). Evidence indicates that head and neck cancer patients undergoing radiotherapy show decreased leptin levels after radiotherapy treatment. Thus, we investigated, through phenotypic and molecular analyses, whether leptin can compromise the therapeutic effect of ionizing radiation and neoplastic behavior of OSCC cells. METHODS: The human OSCC-derived cell lines SCC9 and SCC4 were treated with human recombinant leptin and exposed to 6 Gy of irradiation. We performed the in vitro assays of cell migration, death, proliferation, and colony-forming ability. The reactive oxygen species (ROS) levels and proteome analysis by mass spectrometry were also conducted. RESULTS: Leptin was able to increase cell proliferation, migration, and colony-forming ability, despite the suppressive effect induced by irradiation. Furthermore, the leptin promoted a significant reduction of ROS intracellular accumulation, and increased expression of the cancer-related proteins, as ACTC1, KRT6A, and EEF2 in irradiated OSCC cells. CONCLUSIONS: Our findings suggest that leptin impairs responsivity of OSCC cells to the ionizing radiation, reducing the suppressive effects of irradiation on the neoplastic phenotype, and increasing protein expression critical to carcinogenesis.

Disfunção cardíaca induzida por obesidade genética e dietética: modulação pelo trânsito de cálcio / Cardiac dysfunction induced by genetic and dietetic obesity: modulation by calcium handling

Introdução: A obesidade é considerada importante problema de saúde pública e fator de risco para o desenvolvimento de doenças cardiovasculares. Estudos apontam que o trânsito de cálcio (Ca+2) intracelular e extracelular, mecanismo essencial no acoplamento excitação-contração-relaxamento cardíaco, está envolvido nesse processo patológico. Enquanto o influxo de Ca+2 promove aumento da concentração de Ca+2 livre no citosol na fase de contração, a recaptura e a extrusão do Ca+2 são importantes para a diminuição do Ca+2 intracelular durante o relaxamento. Objetivo: Identificar, baseado na literatura científica, a modulação da disfunção cardíaca pelo trânsito de cálcio em modelos de obesidade genética e dietética. Métodos: A busca de artigos em bases de dados eletrônicas foi realizada com palavras-chaves e seus correspondentes em inglês. Resultados: Inicialmente os artigos que apresentassem uma das palavras-chaves no título foram selecionados. Após processo de triagem, foram identificados 23 artigos para leitura na íntegra. Foram selecionados ao debate na seção "Discussão" apenas 18 artigos, visto que apresentaram conteúdo satisfatório sobre o tema abordado. Conclusão: A literatura mostra que a obesidade, genética ou dietética, promove disfunções cardíacas moduladas por diversas alterações no trânsito de Ca+2 intracelular e em suas proteínas regulatórias.

Introduction: Obesity is considered an important public that presents increasing prevalence on a global scene. Obese individuals have greater susceptibility to the development of cardiac disease. Studies show that calcium (Ca2+) handling, essential mechanism in the process contraction-relaxation of the cardiac muscle, is associated with cardiac dysfunction in obesity models. While Ca2+ influx promotes elevation of free Ca2 + concentration in the cytosol in the contraction period, the recapture and extrusion Ca2 + are important to Ca2+ reduction during the relaxation. Objective: To identify, based on scientific literature, modulation of cardiac function by calcium handling impairments in models of genetic and dietetic obesity. Methods: The search for articles in electronic databases was performed with key words. Results: Initially studies that showed in title one of the key words were selected for analysis. 23 articles were obtained for reading in full. Then, 18 relevant articles were identified on cardiac dysfunction in obesity, both genetic and dietary and participation of the intracellular calcium handling. Conclusion: The literature presents that both genetic and dietetic obesity promotes cardiac dysfunction modulated by various changes in traffic intracellular Ca2+ and its regulators protein.

Leptin and leptin receptor expressions in prostate tumors may predict disease aggressiveness?

The aim of this study was to evaluate the expression of leptin and its receptor in histological sections of prostate tumors, and their association with prognostic factors. A total of 532 surgical specimens from prostate cancer were studied. After histopathological diagnosis, the samples were included in tissue microarrays containing cores from tumor and non-tumor (benign prostatic hyperplasia) areas. These were immunostained with anti-leptin and anti-leptin-receptor antibodies. Objective and subjective analyses were performed. Student's-t-test and ANOVA were used to compare mean values, and linear regression was used to evaluate the correlation between histological results and prognostic indicators. Leptin receptor expression was reduced in tumors with a positive surgical margin, urethral margin involvement, and seminal vesicles invasion. Further, there was a negative correlation between the expression of leptin receptor in tumor areas and the sum of prognostic factors, suggesting that leptin receptor may predict the aggressiveness of disease. Our findings suggest that leptin receptor expression is a potential prognostic factor for PCa. Further investigation is needed to support the use of leptin receptor as a novel biomarker, although leptin itself does not seem to predict the aggressiveness of prostate cancer.(AU)

Metabolic programming of lipid profile and reproductive organs weight by leptin treatment on early life / Programação metabólica do perfil lipídico e peso dos órgãos do sistema reprodutor pelo tratamento com leptina nos primeiros dias de vida

PURPOSE: To evaluate whether the neonatal leptin treatment during the first days of life can program the male reproductive organs weight and the lipid profile. METHODS: At birth 6 dams were divided into 2 groups: Leptin - each pup was injected with 50μL of recombinant rat leptin (80ng/g BW, sc), for the first 10 d of lactation; Control - each pup received the same volume of saline. After weaning, all pups received unlimited access to food until 190 days of age when they were killed. Values are given as mean ± SEM of 6 animals and Test t Student was used to analyze the results. RESULTS: The leptin treatment resulted in a significant increase in body weight (Control= 411.8±16.31; Leptin= 481.8±11.29, p=0.005) and food consumption (Control= 25.32±0.09; Leptin= 32.42±0.15, p=0.0001) and a significant reduction in triglycerides levels (Control= 540.0±117.9; Leptin= 93.25±15.21, p=0.006) and in the weight of hypothalamus (Control= 0.234±0.016; Leptin= 0.154±0.015, p=0.007), pituitary (Control= 0.104±0.0120; Leptin= 0.033±0.012, p=0.003), testis (Control= 3.75±0.055; Leptin= 3.19±0.10, p=0.002) and prostate (Control=1.641±0.1389; Leptin= 0.91±0.07, p=0.001). CONCLUSION: Leptin treatment on the first days of life can program the reproductive organs weight and the lipid profile of the progeny.(AU)

OBJETIVO: Avaliar se o tratamento neonatal com leptina durante os primeiros dias de vida poderia programar o peso dos orgãos do sistema reprodutor masculino e o perfil lipídico. MÉTODOS: Ao nascimento seis ratas-mãe foram distribuídas em dois grupos: Leptina - cada filhote recebeu 50μL de leptina recombinante (80ng/gPC, SC) nos primeiros 10 dias de lactação; Controle - cada filhote recebeu o mesmo volume de salina. Após o desmame, todos os filhotes tiveram acesso ilimitado a ração até 190 dias de idade quando foram mortos. Os dados são expressos como média ± erro padrão e foram analisados pelo teste t Student. RESULTADOS: O tratamento com leptina resultou em aumento significativo no peso corporal (Control= 411.8±16.31; Leptin= 481.8±11.29, p=0.005) e consumo alimentar (Control= 25.32±0.09; Leptin= 32.42±0.15, p=0.0001) e redução significativa nos níveis séricos de triglicerídeos (Control= 540.0±117.9; Leptin= 93.25±15.21, p=0.006), no peso do hipotálamo (Control= 0.234±0.016; Leptin= 0.154±0.015, p=0.007), hipófise (Control= 0.104±0.0120; Leptin= 0.033±0.012, p=0.003), testículo (Control= 3.75±0.055; Leptin= 3.19±0.10, p=0.002) e próstata (Control=1.641±0.1389; Leptin= 0.91±0.07, p=0.001). CONCLUSÃO: O tratamento com leptina nos primeiros dias de vida pode programar o peso dos órgãos do sistema reprodutor e o perfil lipídico da prole.(AU)

Obesidade, adipocitocinas e gravidez: uma atualização da literatura / Obesity, adipocytokines and pregnancy: an update of the literature

Atualmente, a obesidade é considerada um dos maiores e mais visíveis, porém mais negligenciados, problemas de saúde pública em todo o mundo. A adiposidade visceral, mais do que a subcutânea, é determinante para o aparecimento de doenças como o diabetes mellitus, a hipertensão arterial e a doença vascular coronariana. Fisiologicamente, as alterações no metabolismo dos carboidratos e dos lipídios ocorrem na gravidez para garantir um fornecimento contínuo de nutrientes para feto em crescimento promovendo um estado de resistência à insulina (RI). Além dos hormônios placentários, citocinas pró-inflamatórias, as adipocitocinas, secretadas por células do tecido adiposo e pela placenta, desempenham um papel significativo na instalação e manutenção desta RI na gravidez. Nesta revisão, procuramos atualizar o conhecimento sobre as alterações promovidas pelas adipocitocinas e pela obesidade central no organismo da gestante, ressaltando o diagnóstico da adiposidade visceral na gravidez e o risco que envolve este tipo de obesidade para a gestante.

Currently, obesity is considered one of the largest and most visible, but most neglected, public health problems worldwide. The visceral adiposity, rather than subcutaneously, is crucial to the emergence of diseases such as diabetes mellitus, hypertension and coronary vascular disease. Physiologically, changes in the metabolism of carbohydrates and lipids occur in pregnancy to ensure a continuous supply of nutrients to the growing fetus by promoting a state of insulin resistance (IR). In addition to the placental hormones, proinflammatory cytokines, the adipocytokines, secreted by fat tissue and the placenta, play a significant role in the installation and maintenance of IR in pregnancy. In this review, we present the knowledge of the changes promoted by adipocytokines and obesity in the central body of the mother, emphasizing the diagnosis of visceral fat in pregnancy and the risks surrounding this type of obesity in pregnant women.

Restrição alimentar e os mecanismos endócrinos associados ao desenvolvimento folicular ovariano em vacas / Feeding restriction and the endocrine mechanisms involved in ovarian follicular development in cows

Em ruminantes, a nutrição afeta as concentrações circulantes e as reservas hipofisárias de gonadotrofinas, as quais são importantes para o desenvolvimento final de folículos dominantes. Assim, qualquer fator que interfira na sua secreção será limitante ao desempenho reprodutivo. A nutrição pode influenciar a função ovariana por modular a secreção dos hormônios luteinizante (LH) e folículo estimulante (FSH) tanto em condições de alta quanto de baixa ingestão alimentar. O desenvolvimento dos folículos ovarianos também está relacionado com as mudanças na concentração dos hormônios metabólicos periféricos, como: insulina, hormônio do crescimento (GH), leptina, fator de crescimento semelhante à insulina (IGF-I) e neuropeptídeo-Y (NPY), cujas concentrações podem ser afetadas pelo estado metabólico do animal.

In ruminants, the nutrition effect on the blood and pituitary gonadotropins which are important to the final maturation of dominant follicles. Thus, any factor that interferes in their secretion will limit animal reproductive performance. Nutrition may influence the ovarian function by modulating luteinizing hormone (LH) secretion and follicle stimulating hormone (FSH) secretion, either in high or low feed intake condition. Development of ovarian follicles is also related to changes in peripheral metabolites hormones concentrations like: insulin, growth hormone (GH), leptin, insulin-like growth factor-I (IGF-I) and neuropeptide-Y (NPY), whose concentrations may be affected by animal metabolic status.

Restrição alimentar e os mecanismos endócrinos associados ao desenvolvimento folicular ovariano em vacas / Feeding restriction and the endocrine mechanisms involved in ovarian follicular development in cows

Em ruminantes, a nutrição afeta as concentrações circulantes e as reservas hipofisárias de gonadotrofinas, as quais são importantes para o desenvolvimento final de folículos dominantes. Assim, qualquer fator que interfira na sua secreção será limitante ao desempenho reprodutivo. A nutrição pode influenciar a função ovariana por modular a secreção dos hormônios luteinizante (LH) e folículo estimulante (FSH) tanto em condições de alta quanto de baixa ingestão alimentar. O desenvolvimento dos folículos ovarianos também está relacionado com as mudanças na concentração dos hormônios metabólicos periféricos, como: insulina, hormônio do crescimento (GH), leptina, fator de crescimento semelhante à insulina (IGF-I) e neuropeptídeo-Y (NPY), cujas concentrações podem ser afetadas pelo estado metabólico do animal.(AU)

In ruminants, the nutrition effect on the blood and pituitary gonadotropins which are important to the final maturation of dominant follicles. Thus, any factor that interferes in their secretion will limit animal reproductive performance. Nutrition may influence the ovarian function by modulating luteinizing hormone (LH) secretion and follicle stimulating hormone (FSH) secretion, either in high or low feed intake condition. Development of ovarian follicles is also related to changes in peripheral metabolites hormones concentrations like: insulin, growth hormone (GH), leptin, insulin-like growth factor-I (IGF-I) and neuropeptide-Y (NPY), whose concentrations may be affected by animal metabolic status.(AU)

O processo puberal normal / Normal puberty

Definido como o período de transição entre a infância e a vida adulta, o processo puberal objetiva a aquisição damaturidade sexual completa. Esse processo caracteriza-se pelo desenvolvimento dos caracteres sexuais secundáriose pelo estirão de crescimento, que ocorrem sob a regulação principal dos esteróides sexuais e do hormônio do crescimento. A ativação do eixo hipotálamo-hipófise-gonadal consiste no principal evento neuroendócrino associado ao desencadeamento da puberdade, porém os mecanismos que levam a essa ativação permanecem desconhecidos. Dentre as teorias propostas, a mais recente delas relaciona o início do processo puberal à ação da leptina, um hormônio secretado pelos adipócitos, que foi recentemente descoberto