Molecular and Cellular Mechanisms Underlying the Cardiac Hypertrophic and Pro-Remodelling Effects of Leptin.

Since its initial discovery in 1994, the adipokine leptin has received extensive interest as an important satiety factor and regulator of energy expenditure. Although produced primarily by white adipocytes, leptin can be synthesized by numerous tissues including those comprising the cardiovascular system. Cardiovascular function can thus be affected by locally produced leptin via an autocrine or paracrine manner but also by circulating leptin. Leptin exerts its effects by binding to and activating specific receptors, termed ObRs or LepRs, belonging to the Class I cytokine family of receptors of which six isoforms have been identified. Although all ObRs have identical intracellular domains, they differ substantially in length in terms of their extracellular domains, which determine their ability to activate cell signalling pathways. The most important of these receptors in terms of biological effects of leptin is the so-called long form (ObRb), which possesses the complete intracellular domain linked to full cell signalling processes. The heart has been shown to express ObRb as well as to produce leptin. Leptin exerts numerous cardiac effects including the development of hypertrophy likely through a number of cell signaling processes as well as mitochondrial dynamics, thus demonstrating substantial complex underlying mechanisms. Here, we discuss mechanisms that potentially mediate leptin-induced cardiac pathological hypertrophy, which may contribute to the development of heart failure.

Leptin promotes proliferation of human undifferentiated spermatogonia by activating the PI3K/AKT/mTOR pathway.

BACKGROUND: Male infertility is a common disease affecting male reproductive health. Leptin is an important hormone that regulates various physiological processes, including reproductive function. However, few experimental studies have been carried out to elucidate the mechanism of leptin's effects on male reproductive function. OBJECTIVE: The purpose of this study was to investigate the effects of leptin on testicular spermatogenesis and its mechanism, so as to provide potential targets for the treatment of patients with spermatogenic dysfunction. METHODS: Testicular tissues were collected from eight prostate cancer patients undergoing surgical castration. GPR125-positive spermatogonia were isolated by two consecutive magnetic activated cell sorting (MACS), followed by incubation with conditioned medium. To identify the signaling pathway(s) involved in the effects of leptin, undifferentiated spermatogonia were treated with different concentrations of leptin and antagonists of leptin-related pathways. The proliferative effect of leptin was evaluated by cell counting using a hemocytometer. Expressions of p-AKT, p-ERK, p-STAT, and p-S6K were determined by western blotting analysis. RESULTS: Leptin promoted the growth of human GPR125-positive spermatogonia in a concentration-dependent manner. The most significant proliferative effect was observed using 100 ng/mL leptin after 6 days of culture. Leptin significantly increased the phosphorylation of STAT3, AKT, and ERK in undifferentiated spermatogonia. Phosphatidylinositol 3-kinase (PI3K) inhibitor LY294002 inhibited the leptin-induced activation of AKT, ERK, and downstream S6K. Treatment with the mammalian target of rapamycin (mTOR) inhibitor rapamycin also inhibited S6K phosphorylation. Moreover, both LY294002 and rapamycin were found to inhibit the leptin-induced proliferation of undifferentiated spermatogonia. These results suggested that the leptin-induced proliferation of GPR125-positive spermatogonia was dependent on the PI3K/AKT/mTOR pathway. Further exploration of proliferation and apoptotic markers suggested that leptin may alleviate cell apoptosis by regulating the expression of Bax and FasL. CONCLUSIONS: A certain concentration of leptin (25∼100 ng/mL) could promote proliferation of undifferentiated spermatogonia, which was mediated by PI3K/AKT/mTOR pathway.

Legume consumption increase adiponectin concentrations among type 2 diabetic patients: A randomized crossover clinical trial / El consumo de legumbres aumenta las concentraciones de adiponectina en pacientes con diabetes tipo 2: un ensayo clínico aleatorizado cruzado

Background and objective: This randomized crossover clinical trial investigated the effects of substituting legumes for meat consumption in the therapeutic lifestyle change (TLC) diet on leptin and adiponectin concentrations among type 2 diabetic patients. Material and methods: Thirty-one type 2 diabetic patients (24 women, age: 58.1±6.0 years) were randomly assigned to groups designated to consume a legume-free TLC diet or a legume-based TLC diet for 8 weeks. Both diets were similar except for the replacement of two servings of red meat with legumes 3 days per week in the legume-based TLC group. Leptin and adiponectin concentrations were measured at baseline and after the 8-week intervention. Results: The legume-based TLC diet significantly increased adiponectin concentrations in comparison with the legume-free TLC diet. There was no significant change in leptin concentrations after both intervention diets. Conclusions: Legumes increased serum adiponectin concentrations in type 2 diabetic patients. Registration number: IRCT201202251640N7

Antecedentes y objetivo: Este ensayo clínico cruzado aleatorizado investigó los efectos de la sustitución de legumbres por el consumo de carne en la dieta de Cambio Terapéutico en el Estilo de Vida (CTEV) sobre las concentraciones de leptina y adiponectina en pacientes con diabetes tipo 2. Material y métodos: Treinta y un pacientes diabéticos tipo 2 (24 mujeres, edad: 58,1±6,0 años) fueron asignados aleatoriamente a grupos designados para consumir una dieta CTEV libre de legumbres o una dieta CTEV basada en legumbres durante 8 semanas. Ambas dietas fueron similares, excepto por el reemplazo de 2 porciones de carne roja por legumbres 3 días por semana en el grupo de CTEV basado en leguminosas. Las concentraciones de leptina y adiponectina se midieron al inicio y después de la intervención de 8 semanas. Resultados: La dieta de CTEV basada en legumbres aumentó significativamente los niveles de adiponectina en comparación con la dieta de CTEV sin legumbres. No hubo cambios significativos en las concentraciones de leptina después de ambas dietas de intervención. Conclusiones: Las leguminosas aumentaron las concentraciones séricas de adiponectina en pacientes diabéticos tipo 2. Número de registro: IRCT201202251640N7

Leptin and its actions on reproduction in males / 亚洲男科学杂志(英文版)

Leptin, an adipocyte-derived hormone, serves numerous physiological functions in the body, particularly during puberty and reproduction. The exact mechanism by which leptin activates the gonadotropin-releasing hormone (GnRH) neurons to trigger puberty and reproduction remains unclear. Given the widespread distribution of leptin receptors in the body, both central and peripheral mechanisms involving the hypothalamic-pituitary-gonadal axis have been hypothesized. Leptin is necessary for normal reproductive function, but when present in excess, it can have detrimental effects on the male reproductive system. Human and animal studies point to leptin as a link between infertility and obesity, a suggestion that is corroborated by findings of low sperm count, increased sperm abnormalities, oxidative stress, and increased leptin levels in obese men. In addition, daily leptin administration to normal-weight rats has been shown to result in similar abnormalities in sperm parameters. The major pathways causing these abnormalities remain unidentified; however, these adverse effects have been attributed to leptin-induced increased oxidative stress because they are prevented by concurrently administering melatonin. Studies on leptin and its impact on sperm function are highly relevant in understanding and managing male infertility, particularly in overweight and obese men.

Papel de la leptina como señal aferente en la regulación de la homeostasis energética / Role of leptin as afferent signal of energy homeostasis regulation

La obesidad es una enfermedad crónica caracterizada por un aumento patológico de grasa corporal generado por un desbalance entre los ingresos y los egresos energéticos; este exceso de energía se almacena en el tejido adiposo, el cual no solo almacena lípidos, sino que secreta numerosas hormonas, por lo que constituye el órgano endocrino de mayor tamaño del organismo. A diferencia de otras glándulas endocrinas, su masa es variable y puede aumentar o disminuir progresivamente de tamaño dependiendo de la edad, la ingesta alimentaria, la actividad física, la programación perinatal y la predisposición genética; se destaca dentro de los factores secretados la leptina, la cual participa en la regulación del balance energético y la secreción de gonadotropinas.El objetivo de la presente revisión bibliográfica es describir el papel de la leptina como señal aferente en la regulación de la homeostasis energética, y se destaca su importancia como uno de los mecanismos implicados en la patogénesis de la obesidad.

Obesity is a chronic disease characterized by a pathological rise of body fat generated by an imbalance between energy input and output. This energy excess is stored in the adipose tissue which not only stores lipids but also secretes numerous hormones and represents the biggest endocrine organ of the human body. Unlike other endocrine glands, it has a variable mass and may gradually increase or decrease its size depending on age, food intake, physical activity, perinatal scheduling and genetic predisposition. Among the secreted factors are leptin which participates in the regulation of energy balance and the gonadotropin secretions. The objective of this literature review was to describe the role of leptin as afferent signal in the regulation of energy homeostasis; its importance as one of the mechanisms involved in obesity pathogenesis was underlined.

Papel de la leptina como señal aferente en la regulación de la homeostasis energética / Role of leptin as afferent signal of energy homeostasis regulation

La obesidad es una enfermedad crónica caracterizada por un aumento patológico de grasa corporal generado por un desbalance entre los ingresos y los egresos energéticos; este exceso de energía se almacena en el tejido adiposo, el cual no solo almacena lípidos, sino que secreta numerosas hormonas, por lo que constituye el órgano endocrino de mayor tamaño del organismo. A diferencia de otras glándulas endocrinas, su masa es variable y puede aumentar o disminuir progresivamente de tamaño dependiendo de la edad, la ingesta alimentaria, la actividad física, la programación perinatal y la predisposición genética; se destaca dentro de los factores secretados la leptina, la cual participa en la regulación del balance energético y la secreción de gonadotropinas. El objetivo de la presente revisión bibliográfica es describir el papel de la leptina como señal aferente en la regulación de la homeostasis energética, y se destaca su importancia como uno de los mecanismos implicados en la patogénesis de la obesidad(AU)

Obesity is a chronic disease characterized by a pathological rise of body fat generated by an imbalance between energy input and output. This energy excess is stored in the adipose tissue which not only stores lipids but also secretes numerous hormones and represents the biggest endocrine organ of the human body. Unlike other endocrine glands, it has a variable mass and may gradually increase or decrease its size depending on age, food intake, physical activity, perinatal scheduling and genetic predisposition. Among the secreted factors are leptin which participates in the regulation of energy balance and the gonadotropin secretions. The objective of this literature review was to describe the role of leptin as afferent signal in the regulation of energy homeostasis; its importance as one of the mechanisms involved in obesity pathogenesis was underlined(AU)

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.

Papel de la leptina en la fisiología y fisiopatología oral / Leptin’s role in oral physiology and physiopathology

Hace 20 años se caracterizó por primera vez a la leptina, como un péptido anorexigénico que actúa a nivel del hipotálamo y desde entonces se le ha descrito un papel clave en el funcionamiento de una gran diversidad de tejidos, siendo la boca un sitio blanco para muchas funciones mediadas por este péptido, tales como la inducción del crecimiento y diferenciación de diversos tejidos dentales y periodontales, la modulación de la percepción del sabor dulce en las papilas gustativas, la regulación de la deglución y la activación de la respuesta inmunológica. Por otra parte, la leptina juega un papel importante en la mediación de la respuesta ante diferentes agentes agresores en la boca, como las bacterias periodontopatógenas y el alcohol, además participa en ciertos tipos de cáncer en esta cavidad. Este resumen pretende dar una visión general de los diferentes roles que cumple la leptina a nivel bucal descritos hasta la fecha, comenzando por su función en la boca sana, hasta llegar a su participación en la fisiopatología bucal.

Leptin was characterized for the first time 20 years ago as an anorexigenic peptide that acts on the hypothalamus and has since been described as having a key role in the functioning of a great number of tissues. The mouth is one of the areas of the body where this peptide influences processes, such as growth induction and differentiation of various dental and periodontal tissues, modulation of sweet tastes’ perception in the taste buds, swallowing regulation and immune response activation. Moreover, leptin also plays an important role in mediating the response to different oral aggressors, such as periodontopathic bacteria and alcohol, as well as its involvement in certain types of mouth cancer. This review aims to provide an overview of leptin’s known roles on the oral cavity to date, ranging from its function in a healthy mouth to its involvement in oral physiopathology.

Nuevas proyecciones fisiológicas, patológicas y terapéuticas de la leptina / Novel physiological and therapeutic implications of leptin

The adipose tissue is an endocrine organ that produces a variety of protein hormones. One of them is leptin, which regulates several critical functions at the central nervous system such as caloric intake, basal energy expenditure, reproduction, glucose and lipid metabolism and osteogenesis. Acting at a local level, leptin modulates the immune system and promotes liver fibrogenesis. The most promising therapeutic implications of leptin will possibly be in type 1 diabetes mellitus (DM1). Its supplementation in animal models of DM1 prevents hyperglycemia and ketoacidosis. These actions depend on the activation of leptin receptors in the central nervous system and the suppression of glucagon signaling in the liver.

Relação entre leptina, obesidade e exercício físico / Relationship between leptin, obesity and physical exercise

A obesidade é uma doença complexa, com etiologia multifatorial, que afeta todas as idades e classes sociais. No Brasil, o crescimento da obesidade e sobrepeso é preocupante, sendo o Rio Grande do Sul (RS) o estado com os maiores índices. O tecido adiposo é responsável pela síntese de leptina, um hormônio participante da inibição da fome via hipotálamo. O excesso de peso na obesidade eleva a síntese hormonal dos adipócitos e, consequentemente, os níveis plasmáticos de leptina. Contudo, a demasiada estimulação da leptina em seus receptores centrais origina uma resistência à sua ação no organismo. Assim, este excesso acarreta um desequilíbrio entre a ingestão de alimentos e o gasto energético, além de efeitos pró-inflamatórios. A perda de peso é capaz de reestabelecer este equilíbrio, melhorando a qualidade de vida dos indivíduos. O treinamento físico vem sendo estudado como uma alternativa não farmacológica para essa modulação, entretanto muitos resultados controversos são encontrados. O objetivo deste artigo é mostrar a relação da leptina com a obesidade e sua modulação pelo exercício, por meio de uma revisão em torno de artigos científicos sobre este tema (AU)

Obesity is a complex disease with multifactorial etiology which affects people of all ages and classes. In Brazil, the growth in overweight and obesity rates is alarming, and Rio Grande do Sul (RS) presents the highest rates among states. The adipose tissue is responsible for the synthesis of leptin, a hormone which acts in the hypothalamus to inhibit appetite. In overweight people, leptin synthesis is increased, leading to high plasma leptin levels. However, excessive stimulus of leptin central receptors results in resistance to the effects of leptin. This leads to an imbalance between food intake and energetic expenditure, in addition to proinflammatory effects. Weight loss is enough to restore balance and improve quality of life. Physical training is one of the most studied nonpharmacological alternatives to this modulation, although many controversial results have been found. This paper aimed to conduct a review of articles on the relationship between leptin and obesity and its modulation through exercise (AU)

Leptin: molecular mechanisms, systemic pro-inflammatory effects, and clinical implications / Leptina: mecanismos moleculares, efeitos pró-inflamatórios sistêmicos e implicações clínicas

Leptin, the adipokine produced mainly by the white adipose tissue, plays important roles not only in the regulation of food intake, but also in controlling immunity and inflammation. It has been widely demonstrated that the absence of leptin leads to immune defects in animal and human models, ultimately increasing mortality. Leptin also regulates inflammation by means of actions on its receptor, that is widely spread across different immune cell populations. The molecular mechanisms by which leptin determines its biological actions have also been recently elucidated, and three intracellular pathways have been implicated in leptin actions: JAK-STAT, PI3K, and ERK 1/2. These pathways are closely regulated by intracellular proteins that decrease leptin biological activity. In this review, we discuss the molecular mechanisms by which leptin regulates immunity and inflammation, and associate those mechanisms with chronic inflammatory disorders. Arq Bras Endocrinol Metab. 2012;56(9):597-607.

A leptina, uma adipocina produzida principalmente pelo tecido adiposo branco, tem um papel importante não somente na regulação da ingestão alimentar, mas também no controle da imunidade e da inflamação. Já foi amplamente demonstrado que a ausência de leptina causa deficiências imunológicas em modelos animais e em humanos, levando ao aumento da mortalidade. A leptina também regula a inflamação por meio da ação em seu receptor, amplamente distribuído em diversos tipos de células do sistema imunológico. Os mecanismos moleculares pelos quais a leptina determina suas ações biológicas foram recentemente elucidados, e três cascatas intracelulares são ativadas pela leptina: JAK-STAT, PI3K e ERK 1/2. Essas cascatas são reguladas por proteínas intracelulares, reduzindo as ações da leptina. Nesta revisão, são discutidos os mecanismos moleculares pelos quais a leptina regula a imunidade e a inflamação, associando-os a enfermidades inflamatórias crônicas. Arq Bras Endocrinol Metab. 2012;56(9):597-607.

Leptina e aldosterona na atividade simpática na hipertensão resistente, com ou sem Diabetes Tipo 2 / Leptin and aldosterone in sympathetic activity in resistant hypertension with or without type 2 diabetes

FUNDAMENTO: A descoberta da leptina como um estimulador da atividade simpática trouxe uma nova perspectiva para os mecanismos fisiopatológicos da obesidade-hipertensão. OBJETIVO: Avaliamos a relação entre a atividade simpática aumentada e as concentrações plasmáticas de leptina e aldosterona em Hipertensos Resistentes (HR), comparando os grupos com e sem Diabetes Tipo 2 (DT2). MÉTODOS: Vinte e cinco pacientes HR foram avaliados por eletrocardiografia ambulatorial para análise da Variabilidade da Frequência Cardíaca (VFC) nos domínios do tempo e frequência, os quais foram estratificados em dois períodos: 24 horas e período Diurno (D), compreendendo as medidas entre 14 e 18h (domínio do tempo) e uma hora às 15h (domínio da frequência). RESULTADOS: O grupo DT2 (n = 10) apresentou maiores concentrações de aldosterona e leptina que o grupo não DT2 (n = 15) (26,0 ± 11,5 vs. 16,9 ± 7,0 ng/dL - p = 0,021; 81,368.7 ± 47,086.1 vs. 41,228.1 ± 24,523.1 pg/mL - p = 0,048, respectivamente). Houve correlação entre aldosterona e VFC no domínio da frequência em ambos os grupos. Não-DT2 apresentaram a aldosterona correlacionada com D baixa frequência em unidades normalizadas (BFnu) (r = 0,6 [0,12 - 0,85] p = 0,018) e D alta frequência em unidades normalizadas (AFnu) (r = -0,6 [-0,85 - -0,12] p = 0,018). No grupo com diabetes, a aldosterona correlacionou-se com DBFnu (r = 0,72 [0,16 - 0,93] p = 0,019) e DAFnu (r = -0,72 [-0,93 - -0,16] p = 0,019). Apesar da importância da leptina na atividade simpática aumentada na hipertensão, não houve correlação com VFC. CONCLUSÃO: A aldosterona parece estimular a atividade simpática em HR com ou sem DT2. Essa informação combinada com a eficácia clínica dos bloqueadores de receptor mineralocorticoide em HR pode reforçar a aldosterona como alvo terapêutico relevantes em HR. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

BACKGROUND: The finding of adipocyte-derived hormone leptin as an overstimulator of sympathetic activity brought a new perspective to the pathophysiological mechanisms of obesity-hypertension. OBJECTIVES: As aldosterone also increases sympathetic activity, we aimed to assess the relationship between sympathetic overactivity and plasma leptin and aldosterone levels in resistant hypertension (RHTN), comparing the groups with and without T2D. METHODS: Twenty-five RHTN patients underwent ambulatory electrocardiography to analyze heart rate variability (HRV) in time and frequency domains, which were stratified into two periods: 24 hours and daytime (DT), comprising the records between 2:00 p.m to 6:00 p.m (time domain) and one hour at 3:00 p.m (frequency domain). RESULTS: T2D group (n=10) had higher serum aldosterone and plasma leptin levels than the non-T2D (n=15) (26.0±11.5 vs. 16.9±7.0 ng/dL - p=0.021; 81.368.7±47.086.1 vs 41.228.1±24.523.1 pg/mL - p=0.048, respectively). Both groups had aldosterone correlated with HRV in frequency domain. Non-T2D had aldosterone correlated with DT low frequency in normalized units (LF nu) (r=0.6 [0.12-0.85] p=0.018) and DT high frequency in normalized units (HF nu) (r=-0.6 [-0.85- -0.12] p=0.018). Type-2-diabetes group had aldosterone correlated with DT LF nu (r=0.72 [0.16-0.93] p=0.019) and DT HF nu (r=-0.72 [-0.93- -0.16] p=0.019). However, despite of the importance of leptin in sympathetic overactivity in hypertension, leptin did not correlate with HRV. CONCLUSION: Aldosterone seems to overdrive sympathetic activity in RHTN with and without T2D. This information combined with the clinical efficacy of mineralocorticoid receptor blocker in RHTN may reinforce that aldosterone is a major player to be a therapeutic target in RHTN. (Arq Bras Cardiol. 2012; [online].ahead print, PP.0-0).

Complicaciones respiratorias de la obesidad / Respiratory Complications of Obesity

La obesidad, bien conocida como factor de riesgo cardiovascular, puede asimismo comportar una importanteafectación respiratoria. Las alteraciones respiratorias relacionadas con la obesidad abarcan desdela simple alteración de la función ventilatoria, sin consecuencias sobre el intercambio gaseoso, hasta lasituación más grave, la insuficiencia respiratoria hipercápnica característica del síndrome de obesidadhipoventilación. Más recientemente se ha señalado la presencia de un incremento de prevalencia de asmade probable etiología multifactorial pero en el que puede desempeñar un papel importante la inflamación.La hipoventilación en el sujeto obeso es el resultado de complejas interacciones que implican a lasalteraciones de la mecánica ventilatoria y a anomalías del control ventilatorio. Otras dos entidades (enfermedadpulmonar obstructiva crónica y síndrome de apnea hipopnea del sueño [SAHS]), frecuentementepresentes en los pacientes obesos, pueden potenciarla o agravarla. La prevalencia de hipoventilación enel obeso se encuentra subestimada y es frecuente que el diagnóstico sólo se establezca con motivo de unaexacerbación o cuando el paciente es estudiado por sospecha de SAHS. El manejo ventilatorio de estospacientes, mediante CPAP o ventilación no invasiva (VNI) dependerá de la situación clínica subyacente yde la presencia o no de otra comorbilidad. Tanto la VNI como la CPAP han mostrado su eficacia no sóloen el control de las alteraciones gasométricas, sino también en la mejora de la calidad de vida y en lasupervivencia de los pacientes(AU)

Obesity, well known as a cardiovascular risk factor, can also lead to significant respiratory complications.The respiratory changes associated with obesity extend from a simple change in respiratory function,with no effect on gas exchange, to the more serious condition of hypercapnic respiratory failure,characteristic of obesity hypoventilation syndrome. More recently, it has been reported that there is anincreased prevalence of asthma which is probably multifactorial in origin, but in which inflammationmay play an important role. Hypoventilation in the obese subject is the result of complex interactionsthat involve changes in the ventilatory mechanics and anomalies in breathing control. Two other conditions(COPD and sleep apnea-hypopnea syndrome [SAHS], often present in obese patients, can triggeror aggravate it. The prevalence of hypoventilation in the obese is under-estimated and the diagnosisis usually established during an exacerbation, or when the patient is studied due to suspicion of SAHS.Ventilatory management of these patients includes either CPAP or NIV. The choice of one or anotherwill depend on the underlying clinical condition and whether or not there is another comorbidity. BothNIV and CPAP have demonstrated their effectiveness, not only in the control of gas exchange, but alsoin improving the quality of life and survival of these patients(AU)

The PI3K signaling pathway mediates the biological effects of leptin / A via de sinalização intracelular da PI3K medeia os efeitos biológicos da leptina

The activation of the leptin receptor recruits several intracellular signaling pathways, including the phosphatidylinositol 3-kinase (PI3K) pathway. While some of the leptin-induced signaling pathways, such as the JAK2/STAT3 pathway, induce cellular responses primarily through changes in gene expression, the PI3K pathway affects cellular properties more rapidly, through post-translational changes such as protein phosphorylation. Accordingly, several studies have shown that the PI3K pathway is required for the acute effects of leptin, such as a leptin-induced decrease in food intake. Leptin signaling through PI3K also affects the electrophysiological properties of neurons, including changes in their membrane potential and firing rates. In this review, we summarize the recent advances in our understanding of the role played by the PI3K signaling pathway in controlling food intake and energy balance. In particular, we focus on the importance of the PI3K signaling pathway as a mediator of the effects of leptin on hypothalamic neurons.

A ativação do receptor de leptina recruta diversas vias de sinalização intracelular, entre elas a via da fosfatidilinositol 3-quinase (PI3K). Enquanto algumas dessas vias, como a sinalização pelo JAK2/STAT3, induzem respostas celulares por meio de mudanças na transcrição gênica, a via da PI3K altera propriedades celulares de forma rápida, via fosforilação de proteínas. Em concordância, estudos mostraram que a via da PI3K é necessária para que a leptina induza seus efeitos agudos, como redução da ingestão alimentar, após administração de leptina. A ativação da PI3K pela leptina também afeta as propriedades fisiológicas de neurônios, incluindo mudanças no potencial de membrana e no potencial de ação. Nesta revisão, resumimos os recentes avanços na compreen-são do papel desempenhado pela via de sinalização da PI3K no controle da ingestão alimentar e do balanço energético. Discutimos, principalmente, como a via da PI3K é importante para mediar os efeitos da leptina sobre os neurônios hipotalâmicos.

Obesidade e doença arterial coronariana: papel da inflamação vascular / Obesidad y enfermedad arterial coronaria: papel de la inflamación vascular / Obesity and coronary artery disease: role of vascular inflammation

A obesidade vem se tornando uma epidemia global. Cerca de 1,1 bilhões de adultos e 10 por cento das crianças do mundo são atualmente considerados portadores de sobrepeso ou obesos. Classicamente associada a fatores de risco para doença cardiovascular, como diabete melito e hipertensão arterial sistêmica, a obesidade vem sendo cada vez mais encarada como fator de risco independente para doença arterial coronariana (DAC). A aterosclerose coronariana compreende uma série de respostas inflamatórias em nível celular e molecular, cujas reações se encontram mais exacerbadas em pacientes obesos. Antes considerado mero depósito de gordura, o tecido adiposo é visto hoje em dia como órgão endócrino e parácrino ativo, produtor de diversas citocinas inflamatórias, como as adipocinas. Este artigo visa alertar para o grave problema de saúde pública em que a obesidade se tornou nas últimas décadas e correlacionar o processo inflamatório exacerbado nos indivíduos obesos com a maior incidência de DAC nessa população.

Obesity is becoming a global epidemic. Around 1.1 billion adults and 10 percent of the world's children are currently overweight or considered obese. Generally associated with risk factors for cardiovascular disease, such as Diabetes Mellitus and systemic arterial high blood pressure, the obesity has been more and more seen as an independent risk factor for Coronary Artery Disease (CAD). Coronary arteriosclerosis comprises a series of inflammatory responses at cellular and molecular level, whose reactions are stronger in obese patients. In the past, the adipose tissue was regarded as a mere fat deposition. Now it is seen from a totally different standpoint, as an active endocrine and paracrine organ that produces several inflammatory cytokines, such as the adipokines. This article aims to raise awareness about obesity as an increasingly significant public health issue over the past decades, as well as to relate the intense inflammatory process in obese individuals with an increased tendency for this group of individuals to develop CAD.

La obesidad se está tornando una epidemia global. Cerca de 1,1 billones de adultos y el 10 por ciento de los niños del mundo están considerados actualmente portadores de sobrepeso u obesos. Clásicamente asociada a factores de riesgo para enfermedad cardiovascular, como diabetes melitus e hipertensión arterial sistémica, la obesidad se está considerando cada vez más factor de riesgo independiente para enfermedad arterial coronaria (EAC). La aterosclerosis coronaria comprende una serie de respuestas inflamatorias a nivel celular y molecular, cuyas reacciones se encuentran más exacerbadas en pacientes obesos. Antes considerado mero depósito de grasa, el tejido adiposo está visto hoy en día como órgano endócrino y parácrino activo, productor de diversas citocinas inflamatorias, como las adipocinas. Este artículo apunta a alertar sobre el grave problema de salud pública en que se convirtió la obesidad en las últimas décadas y correlacionar el proceso inflamatorio exacerbado en los individuos obesos con la mayor incidencia de EAC en esta población.

Leptina: acercamiento hacia una hormona / Leptine: an approach to a hormone

INTRODUCCIÓN: la leptina tiene un importante papel en la patogenia de la obesidad, al informar al hipotálamo del contenido de grasa corporal y regular la ingesta alimentaria, no obstante, esta hormona constituye un elemental mediador de varias funciones fisiológicas en nuestro organismo. MÉTODOS: se realizó una revisión bibliográfica que incluyó un total de 32 documentos de la especialidad de Endocrinología, a fin de describir el mecanismo fisiológico de la leptina y su relación con diversos trastornos neuroendocrinos. RESULTADOS: las concentraciones de leptina son inferiores en el sexo masculino, lo que está en relación con el incremento de testosterona, que ejerce un efecto inhibitorio en su producción. Entre otros de sus efectos fisiológicos, interviene también en la regulación del inicio de la pubertad y participa en la respuesta inflamatoria. CONCLUSIONES: actualmente las posibilidades de tratamiento de la obesidad y otros trastornos de fertilidad con el uso de leptina recombinante estßn abiertas...

INTRODUCTION: leptine has a significant role in obesity pathogeny, which informs to hypothalamus of the body fat content and regulates the food consumption; however, this hormone is a elementary mediator of some physiologic functions in our organism. METHODS: a bibliographic review was carried out including a total of 32 data from Endocrinology specialty, to describe the physiologic mechanism of Leptine, and its relation with diverse neuroendocrine disorders. RESULTS: concentrations of Leptine are lower in male sex a feature related to the testosterone increase exerting an inhibitory effect on its production. Among other physiologic effects is the regulation of puberty onset and it is involved in inflammatory response. CONCLUSIONS: nowadays, obesity treatment possibilities and other fertility disorders related to use of Leptine are open...

Leptina: acercamiento hacia una hormona / Leptine: an approach to a hormone

INTRODUCCIÓN: la leptina tiene un importante papel en la patogenia de la obesidad, al informar al hipotálamo del contenido de grasa corporal y regular la ingesta alimentaria, no obstante, esta hormona constituye un elemental mediador de varias funciones fisiológicas en nuestro organismo. MÉTODOS: se realizó una revisión bibliográfica que incluyó un total de 32 documentos de la especialidad de Endocrinología, a fin de describir el mecanismo fisiológico de la leptina y su relación con diversos trastornos neuroendocrinos. RESULTADOS: las concentraciones de leptina son inferiores en el sexo masculino, lo que está en relación con el incremento de testosterona, que ejerce un efecto inhibitorio en su producción. Entre otros de sus efectos fisiológicos, interviene también en la regulación del inicio de la pubertad y participa en la respuesta inflamatoria. CONCLUSIONES: actualmente las posibilidades de tratamiento de la obesidad y otros trastornos de fertilidad con el uso de leptina recombinante estßn abiertas(AU)

INTRODUCTION: leptine has a significant role in obesity pathogeny, which informs to hypothalamus of the body fat content and regulates the food consumption; however, this hormone is a elementary mediator of some physiologic functions in our organism. METHODS: a bibliographic review was carried out including a total of 32 data from Endocrinology specialty, to describe the physiologic mechanism of Leptine, and its relation with diverse neuroendocrine disorders. RESULTS: concentrations of Leptine are lower in male sex a feature related to the testosterone increase exerting an inhibitory effect on its production. Among other physiologic effects is the regulation of puberty onset and it is involved in inflammatory response. CONCLUSIONS: nowadays, obesity treatment possibilities and other fertility disorders related to use of Leptine are open(AU)