Leptin regulates glucose homeostasis via the canonical Wnt pathway in the zebrafish.

Leptin is best known for its role in adipostasis, but it also regulates blood glucose levels. The molecular mechanism by which leptin controls glucose homeostasis remains largely unknown. Here, we use a zebrafish model to show that Wnt signaling mediates the glucoregulatory effects of leptin. Under normal feeding conditions, leptin regulates glucose homeostasis but not adipostasis in zebrafish. In times of nutrient excess, however, we found that leptin also regulates body weight and size. Using a Wnt signaling reporter fish, we show that leptin activates the canonical Wnt pathway in vivo. Utilizing two paradigms for hyperglycemia, it is revealed that leptin regulates glucose homeostasis via the Wnt pathway, as pharmacological inhibition of this pathway impairs the glucoregulatory actions of leptin. Our results may shed new light on the evolution of the physiological function of leptin.

Association of leptin with cardiometabolic factors in schoolchildren and adolescents with congenital adrenal hyperplasia. / Asociación de leptina con factores cardiometabólicos en escolares y adolescentes con hiperplasia suprarrenal congénita.

Introduction: In congenital adrenal hyperplasia (CAH), obesity, hyperinsulinemia and leptin levels are increased. Objective: To identify the frequency of cardiometabolic risk factors (CRF) in children and adolescents with CAH and to explore the relationship with leptin levels. Method: Cross-sectional study of 40 patients who underwent anthropometric measurements and had fasting glucose, insulin, triglycerides, 17-hidroxyprogesterone, leptin, HDL and LDL-cholesterol assessed. The patients were classified according to the number of CRFs, and leptin levels were analyzed with the Kruskal-Wallis test. Pearson's correlation was applied between leptin, body mass index (BMI) z-score and body fat percentage. Results: Fifty percent of the patients had obesity and overweight, 59% had hypertriglyceridemia, 40%, hypoalphalipoproteinemia, 27.5%, high LDL-cholesterol and 22.5% insulin resistance. There was positive correlation between leptin and body fat percentage (r = 0.64), BMI z-score (r = 0.55) and the number of CRFs (r = 0.65). In the obesity-adjusted multivariate analysis, leptin levels were associated with the number of CRFs. Conclusion: CAH had a high frequency of CRFs and leptin appeared to be associated with a more adverse cardiometabolic profile in subjects with obesity and overweight.

Introducción: En la hiperplasia suprarrenal congénita (HSC), la obesidad, la hiperinsulinemia y los niveles de leptina se encuentran incrementados. Objetivo: Identificar la frecuencia de los factores de riesgo cardiometabólico (FRC) en niños y adolescentes con HSC y explorar la relación con los niveles de leptina. Método: Estudio transversal de 40 pacientes a quienes se realizó somatometría y evaluación de glucosa, insulina, triglicéridos, 17-hidroxiprogesterona, leptina, colesterol HDL y LDL en ayuno. Los pacientes fueron clasificados por el número de FRC y se analizaron los niveles de leptina con Kruskal-Wallis. Se aplicó correlación de Pearson entre la leptina, puntuación Z del índice de masa corporal (zIMC) y porcentaje de grasa corporal. Resultados: 50 % de los pacientes presentó obesidad y sobrepeso, 59 % hipertrigliceridemia, 40 % hipoalfalipoproteinemia, 27.5 % colesterol LDL alto y 22.5 % resistencia a la insulina. Hubo correlación positiva entre leptina y porcentaje de grasa corporal (r = 0.64), el zIMC (r = 0.55) y el número de FRC (r = 0.65). En el análisis multivariado ajustado por obesidad, los niveles de leptina se asociaron con el número de FRC. Conclusión: La HSC tuvo alta frecuencia de FRC y al parecer la leptina se asoció con perfil cardiometabólico más adverso en sujetos con obesidad y sobrepeso.

Circulating leptin levels in the assessment of Crohn's disease activity and its relation to nutritional status.

Introduction: Objective: to evaluate leptin levels and its relation to nutritional status in Crohn's disease (CD). Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessed using the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included body mass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs. Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,481,222 ng/ml). Significant differences were seen in NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGA scores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showed association between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD. Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional tool for evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improve nutritional status.

Introducción: Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC). Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricional se evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Los indicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, el grosor del pliegue cutáneo del tríceps y la circunferencia de las piernas. Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.481.222 ng/ml). Se observaron diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativas entre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales. La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml como umbral para EC. Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC.La leptina puede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.

Leptin and prolactin reduce cryodamage in normozoospermic human semen samples during cryopreservation.

OBJECTIVES: Cryopreservation has destructive effects on the function and structure of spermatozoa. It is known that leptin and prolactin play an active role in decreasing the rates of reactive oxygen species and DNA fragmentation, as well as enhancing sperm motility. Hence, this experiment aimed to investigate the effects of leptin and prolactin as pro-survival factors on the normozoospermic human semen samples during cryopreservation. MATERIAL AND METHODS: Semen samples were collected from 15 healthy, fertile men ranging from 25 to 40 years. Cryopreservation of the samples was performed in liquid nitrogen over a period of two weeks, using five varying concentrations of leptin/prolactin, 0, 10, 100, 500, and 1000ng/ml respectively. Sperm motility, total caspase activity, and mitochondrial and cytosolic ROS were measured by flowcytometry, TUNEL, and other appropriate tests after thawing of the samples. RESULTS: Both hormones were observed to have positive effects on the motility of the samples post-cryopreservation, the highest improvement being in the 100ng/ml concentration leptin and prolactin in comparison to the control group (P=0.01 and P=0.041, respectively). A significant reduction of mitochondrial ROS was also observed in 100 and 1000ng/ml of leptin (P=0.042), and there was a considerable decrease in the cytosolic ROS in the 100ng/ml of prolactin in comparison to the control group (P=0.048). Total caspase activity was also highly reduced in the 100, 500, and 1000ng/ml of leptin compared to the control group (P=0.039). Interestingly, both hormones also significantly decreased DNA fragmentation in 1000ng/ml compared to the control group (P=0.042). CONCLUSION: It can be concluded that leptin and prolactin act as protective agents against cryodamage to spermatozoa during cryopreservation.

Dietary inflammatory index and its association with leptin and adiponectin in Uygur overweight/obese adults.

Introduction: Introduction: chronic inflammation contributes to a wide range of metabolic disorders through the influence of diet. The dietary inflammatory index (DII) was developed to measure the inflammation potential of diet. Objectives: Uygur adults have a high prevalence of obesity, but the causes of this condition remain unclear. In this study we investigated the association between DII and adipocytokines among overweight and obese Uygur adults. Methods: a total of 283 obese and overweight Uygur adults were included. Sociodemographic characteristics, anthropometric measurements, dietary surveys and biochemical indicators were collected by standardized protocols. The DII score was calculated using a valid and reliable 93-item food frequency questionnaire (FFQ). Linear regression was used to estimate the relationship between DII and adipocytokines. Results: the DII score was 1.35 ± 1.08, ranging from -2.14 to +3.11. There was a significant inverse correlation between DII and high-density lipoprotein cholesterol (HDL-C) in the unadjusted model (ß = -0.12, SE = 0.05, p = 0.02), and this remained after adjustment for age, gender, body mass index (BMI). DII was negatively associated with adiponectin (ADPN) ( = -203.15, p = 0.04) and positively associated with leptin (LEP) concentration ( = 1.64, p = 0.002) after adjustment for age, gender and BMI. Conclusion: a pro-inflammatory diet, as indicated by a higher DII score, is associated with adipose tissue inflammation in Uygur adults and supports the hypothesis that diet may play a role in the development of obesity through inflammatory modulation mechanisms. A healthy anti-inflammatory diet is feasible for obesity intervention in the future.

Introducción: Introducción: la inflamación crónica causa múltiples trastornos metabólicos a través de la influencia de la dieta. El índice de inflamación dietética (DII) se estableció para medir el potencial inflamatorio de la dieta. Objetivo: los adultos uigur presentan una alta prevalencia de obesidad, pero las causas de esta condición aún no están claras. En el presente estudio se investigó la relación entre DII y adipocitocinas en adultos uigur con sobrepeso y obesidad. Métodos: se incluyeron 283 adultos uigur obesos y con sobrepeso. Las características sociodemográficas, antropométricas, dietéticas y bioquímicas se recogieron mediante un protocolo estandarizado. El índice DII se calculó utilizando un cuestionario de frecuencia alimentaria (FFQ) válido y fiable de 93 elementos. Se realizó una regresión lineal para estimar la relación entre DII y adipocitocinas. Resultados: la puntuación DII fue de 1,35 ± 1,08 y osciló entre -2,14 y +3,11. En el modelo no ajustado hubo una correlación negativa significativa entre DII y colesterol lipoproteínico de alta densidad (HDL-C) (ß = -0,12, p = 0,02) que permaneció después de ajustar la edad, el sexo y el índice de masa corporal (IMC). Después de ajustar la edad, el sexo y el IMC, el DII se correlacionó negativamente con la concentración de adiponectina (ß = - 203,15, p = 0,04) y positivamente con la concentración de leptina (ß = 1,64, p = 0002). Conclusión: las puntuaciones más altas de DII sugieren que la dieta proinflamatoria está relacionada con la inflamación del tejido adiposo en los adultos uigur, y apoyan la hipótesis de que la dieta puede desempeñar un papel en el desarrollo de la obesidad a través del mecanismo de regulación de la inflamación. La dieta antiinflamatoria saludable es factible para futuras intervenciones de obesidad.

Body composition and nutritional status changes in adolescents with anorexia nervosa.

INTRODUCTION: Nutritional status assessment in anorexia nervosa (AN) includes the evaluation and monitoring of body composition throughout the treatment period. The gold standard for the study of body composition is dual-energy X-ray absorptiometry (DEXA), although electrical bioimpedance (BIA) is a more accessible, cheaper and faster method that does not involve exposure to radiation. MATERIAL AND METHODS: We recruited 33 female adolescents with AN (age, 11.7-16.3 years) by consecutive sampling. We collected data on clinical, anthropometric and laboratory variables. Patients were assessed with BIA and DEXA at inclusion in the study and at the end of the study, with a mean duration of follow-up of 1 year, during the nutritional rehabilitation phase. RESULTS: There was significant improvement in nutritional status, reflected by the body composition obtained by anthropometric measurements and BIA. The phase angle increased significantly during the follow-up. Greater weight loss was associated with the presence of secondary amenorrhoea and decreased bone mineral density in the spine. CONCLUSIONS: Electrical BIA is a useful tool for assessment and monitoring of nutritional status in paediatric patients with AN. Dual-energy X-ray absorptiometry continues to be essential to assess bone mineral density. The role of hormones such as leptin remains to be elucidated.

The leptin/adiponectin ratio as prognostic marker for dyslipidemia during 1 year of follow-up in pediatric patients receiving kidney replacement therapy.

Introduction: Background: leptin and adiponectin are associated with cardiovascular disease in chronic kidney disease (CKD) patients and could be useful prognostic factors. Objectives. to explore the usefulness of the leptin/adiponectin ratio (LAR) to predict the presence or worsening of dyslipidemia during 1 year of follow-up in children receiving kidney replacement therapy (KRT). Material and methods: a prospective cohort study was performed. Pediatric KRT patients aged between 8 and 17 years who were undergoing hemodialysis or peritoneal dialysis were included. At enrollment, the lipid profile, adiponectin and leptin levels, and somatometric measurements, including body fat percentage, were determined. At the one-year follow-up, the lipid profile was reassessed. Results: of the 70 patients included, the median age was 13 years, and there was no sex predominance (52.8 % males). At the end of follow-up, the patients were divided into three groups: those without dyslipidemia (WOD), those who developed or experienced worsening of their dyslipidemia (DWD) and those with persistent dyslipidemia (PD). A LAR > 0.85 (OR, 16.7) and body fat percentage (OR, 1.46) were associated with an increased risk of PD and DWD at 12 months, independently of urea level, BMI Z-score, benzafibrate treatment, CKD progression time, and replacement treatment. Conclusions: a LAR > 0.85 and fat body percentage at the beginning of follow-up were strongly associated with the presence, persistence or worsening of dyslipidemia at the 12-month follow-up in children with KRT.

Introducción: Antecedentes: la leptina y la adiponectina se asocian con enfermedad cardiovascular en los pacientes con enfermedad renal crónica (ERC) y podrían ser factores pronósticos útiles. Objetivos: explorar la utilidad del cociente leptina/adiponectina (LAR) para predecir la presencia o empeoramiento de la dislipidemia durante 1 año de seguimiento en niños que reciben terapia de reemplazo renal (TRR). Material y métodos: se realizó un estudio de cohortes prospectivo. Se incluyeron pacientes pediátricos con TRR de entre 8 y 17 años que estaban en hemodiálisis o diálisis peritoneal. Al inicio del estudio se determinaron el perfil lipídico, los niveles de adiponectina y leptina, y las mediciones somatométricas, incluido el porcentaje de grasa corporal. En el seguimiento de un año, se reevaluó el perfil de lípidos. Resultados: de los 70 pacientes incluidos, la mediana de edad fue de 13 años y no hubo predominio de sexo (52,8 % de varones). Al final del seguimiento, los pacientes se dividieron en tres grupos: aquellos sin dislipidemia (SD), aquellos que desarrollaron o experimentaron un empeoramiento de su dislipidemia (ED) y aquellos con dislipidemia persistente (PD). Un LAR > 0,85 (OR: 16,7) y el porcentaje de grasa corporal (OR: 1,46) se asociaron con un mayor riesgo de ED y PD a los 12 meses, independientemente del nivel de urea, la puntuación Z del IMC, el tratamiento con benzafibrato, el tiempo de progresión de la ERC y el tratamiento de reemplazo. Conclusiones: un LAR > 0,85 y el porcentaje de grasa corporal al inicio del seguimiento se asociaron fuertemente con la presencia, persistencia o empeoramiento de la dislipidemia a los 12 meses de seguimiento en niños con TRR.

Distribution of leptin receptors in the brain stem: possible route in the pathophysiology of neuromuscular control of airway resistance during sleep.

INTRODUCTION: Leptin, a hormone related to satiety, has been studied because of its association with obesity and sleep apnea. The distribution of leptin receptors in the brain stem, and in the hypoglossal nucleus, has not yet been described. The stimulation of these muscles has been studied in the treatment of sleep apnea. OBJECTIVE: to detail the presence of leptin receptors in the nuclei of these nerves to enable studies of stimulation of this region through leptin. METHODS: the brains of five cadavers, removed during necropsy, collected at the Death Verification Service were included. An informed consent was signed by a family member (wife, mother or son/daughter) who answered specific questionnaire concerning comorbities. Anthropometric measurements were recorded. The medulla oblongata and pons fragments were identified. Immunohistochemical staining analysis was performed to identify the location of the leptin receptors. RESULTS: In the immunohistochemical analysis an intense staining signal of the brownish coloration of neurons was evidenced in the hypoglossal nerve nucleus, moderate in the olivary nucleus and mild in the dorsal nucleus of the vagus and trigeminal nucleus. In motor neurons, more intense brown pigmentation can be observed in the nucleus and cytoplasm when compared to sensory neurons. CONCLUSION: The immunoexpression of leptin receptor was demonstrated in the motor neurons of the human hypoglossal nucleus. These results may contribute to unravel details of the pathophysiology of neuromuscular control of airway collapse during sleep and to the development of new drugs capable of improving the neuromuscular tone of upper airway in apneic individuals.

[Cardiovascular risk and insulin resistance in childhood leukemia survivors]. / Riesgo cardiovascular y resistencia insulínica en supervivientes de leucemia infantil.

Introduction: Material and methods: a retrospective study of childhood acute leukemia survivors. Survivors with a diagnosis of leukemia before 16 years of age in a tertiary hospital, during the period of 1998-2018, were selected, who had completed their treatment at least two years earlier. We examined: blood adipokine levels and carbohydrate metabolism, body composition by bioimpedance, and carotid status by ultrasound. Somatometric measures were also taken. Results: the registry showed 82 children diagnosed with acute leukemia, aged between 6 and 16 years. Only 22 met the criteria to be included in the study. Results reveled that 32 % of the sample met the criteria for overweight-obesity, and 36 % had high insulin resistance indexes (IR). Leptin levels were higher in women (15.45 vs. 3.25; p = 0.044) and in obese and overweight subjects, as was the leptin/adiponectin ratio, which rises in the presence of IR (2.52 vs. 0.45; p = 0.037). We observed an increase in carotid intima-media thickness in relation to BMI (0.008; CI, -0.002 to 0.013; p = 0.007) without any association with an increase in fat mass in these patients (0.204; CI, -0.043 to 0.451; p = 0.101). Conclusions: childhood leukemia survivors have a high cardiovascular risk, characterized by an increase in IR, not associated with an increase in fat mass. This risk could justify the implementation of preventive actions in these long-lived patients.

Introducción: Material y métodos: estudio retrospectivo de supervivientes de leucemia aguda en edad infantil. Se seleccionaron aquellos supervivientes con diagnóstico de leucemia antes de los 16 años de edad, en un hospital de tercer nivel y durante el período 1998-2018, que hubieran finalizado su tratamiento como mínimo dos años antes. Se analizaron: niveles de adipokinas y metabolismo hidrocarbonado en sangre, composición corporal mediante bioimpedancia y evaluación ecográfica carotídea. Se tomaron además datos somatométricos. Resultados: de 82 niños con diagnóstico de leucemia aguda, con edades comprendidas entre 6 y 16 años, incluidos en el registro, solamente 22 cumplieron los criterios para ser incluídos en el estudio. Entre los resultados destaca que el 32 % de la muestra cumplían los criterios de sobrepeso-obesidad y el 36 % presentaban índices de resistencia insulínica (RI) elevados. Los niveles de leptina fueron más elevados en las mujeres (15,45 vs. 3,25; p = 0,044) y en los individuos con obesidad o sobrepeso, así como la ratio leptina/adiponectina, que se eleva en presencia de RI (2,52 vs. 0,45; p = 0,037). Se observó un incremento del grosor mediointimal carotídeo en relación con el IMC (0,008; IC: -0,002 a 0,013; p = 0,007) sin asociarse a un aumento de masa grasa en estos pacientes (0,204; IC: -0,043 a 0,451; p = 0,101). Conclusiones: los pacientes supervivientes de leucemia en la edad infantil tienen un riesgo cardiovascular elevado, caracterizado por un aumento de la RI no asociado a aumento de la masa grasa. Este riesgo podría justificar la implementación de medidas preventivas en estos pacientes, cada vez más longevos.

Relationship of age at menarche and serum leptin with the metabolically unhealthy phenotype in adolescents.

INTRODUCTION: Objective: to analyze the relationship of age at menarche and leptin with the metabolically healthy (MH) and metabolically unhealthy (MUH) phenotypes in adolescent girls in different body mass index (BMI) categories. Method: an observational and cross-sectional study consisting of 139 female adolescents attended to at the Adolescent Reference Center in Macaé, Rio de Janeiro. Menarche was classified as early (EM) when the first menstruation occurred at or before 11 years of age; normal menarche (NM) was categorized at ages 12 to 14; menarche was considered late (LM) when it occurred at age 15 or older. The factors required to ascertain the subjects' phenotype, as well as their leptin levels, weight, and height, were measured and their BMIs were calculated. The girls were classified as MH or MUH based on the NCEP-ATP III criteria as adapted for children and adolescents. Results: 82 % (n = 114) of the girls were classified as MH and 18 % (n = 25) as MUH. Mean age at menarche was 11.79 ± 1.39 years. There was a higher prevalence of MUH amongst the girls who had EM (p = 0.04). A higher inadequacy of serum leptin concentrations was found in girls who had EM (p = 0.05) and in those classified as MUH (p = 0.01). The adolescents who were severely obese exhibited inadequate leptin levels (p < 0.01) and had gone through EM (p = 0.02). A total of 8.1 % (n = 7) of the normal-weight girls were classified as MUH, and 29.4 % (n = 5) of those who were severely obese were classified as MH (p < 0.01). Conclusion: early menarche and high serum leptin concentrations are related with the MUH phenotype in adolescent girls in different BMI categories.

INTRODUCCIÓN: Objetivo: analizar la relación de la edad de la menarquia y los niveles de leptina con los fenotipos metabólicamente saludables (MS) y metabólicamente no saludables (MNS) en adolescentes de diferentes categorías de índice de masa corporal (IMC). Método: estudio observacional y transversal compuesto por 139 adolescentes de sexo feminino, atendidas en el Centro de Referencia para Adolescentes de Macaé, Río de Janeiro. La menarquia se clasificó como precoz (MP) cuando se produjo la primera menstruación a o antes de los 11 años de edad; la menarquia normal (MN) se clasificó como aquella sucedida a la edad de 12 a 14 años; la menarquia se consideró tardía (MT) cuando ocurrió a los 15 años o más. Se midieron los factores necesarios para determinar el fenotipo de los sujetos, y se midieron sus niveles de leptina, peso y altura, y se calculó su IMC. Las adolescentes se clasificaron como MS y MNS según los criterios de NCEP-ATP III, adaptados para niños y adolescentes. Resultados: el 82 % (n = 114) de las adolescentes se clasificaron como MH y el 18 % (n = 25) como MUH. La edad media de la menarquia fue de 11,79 ± 1,39 años. Hubo una mayor prevalencia de MUH entre las adolescentes que tenían MP (p = 0,04). Se encontró una mayor insuficiencia de las concentraciones séricas de leptina en las adolescentes que tenían MP (p = 0,05) y en aquellas clasificadas como MNS (p = 0,01). Las adolescentes que eran severamente obesas exhibieron niveles inadecuados de leptina (p < 0,01) y habían pasado por una MP (p = 0,02). El 8,1 % (n = 7) de las adolescentes de peso normal se clasificaron como MNS y el 29,4 % (n = 5) de las que eran severamente obesas se clasificaron como MS (p < 0,01). Conclusión: la menarquia temprana y las altas concentraciones séricas de leptina están relacionadas con el fenotipo MNS en las adolescentes de diferentes categorías de IMC.

Leptin Gene Protects Against Cold Stress in Antarctic Toothfish.

Leptin is a cytokine-like peptide, predominantly biosynthesized in adipose tissue, which plays an important role in regulating food intake, energy balance and reproduction in mammals. However, how it may have been modified to enable life in the chronic cold is unclear. Here, we identified a leptin-a gene (lepa) in the cold-adapted and neutrally buoyant Antarctic toothfish Dissostichus mawsoni that encodes a polypeptide carrying four α-helices and two cysteine residues forming in-chain disulfide bonds, structures shared by most vertebrate leptins. Quantitative RT-PCR confirmed that mRNA levels of the leptin-a gene of D. mawsoni (DM-lepa) were highest in muscle, followed by kidney and liver; detection levels were low in the gill, brain, intestine, and ovary tissues. Compared with leptin-a genes of fishes living in warmer waters, DM-lepa underwent rapid evolution and was subjected to positive selection. Over-expression of DM-lepa in the zebrafish cell line ZFL resulted in signal accumulation in the cytoplasm and significantly increased cell proliferation both at the normal culture temperature and under cold treatment. DM-lepa over-expression also reduced apoptosis under low-temperature stress and activated the STAT3 signaling pathway, in turn upregulating the anti-apoptotic proteins bcl2l1, bcl2a, myca and mdm2 while downregulating the pro-apoptotic baxa, p53 and caspase-3. These results demonstrate that DM-lepa, through STAT3 signaling, plays a protective role in cold stress by preventing apoptotic damage. Our study reveals a new role of lepa in polar fish.

The role of ghrelin and leptin in feeding behavior: Genetic and molecular evidence.

Feeding behavior is integrated within a wide variety of eating behaviors, which depend on psychosocial, biological and environmental factors. These types of behavior can cause nutrition-related diseases such as obesity, which affects more than 650 million people worldwide. Ghrelin and leptin are key hormones that regulate appetite, food intake and energy metabolism. Research in genetics suggests that genetic variants of both hormones are associated with complex forms of eating behavior, such as a preference for palatable food, making individuals susceptible to the modern obesogenic environment. This review analyses the scientific evidence around polymorphisms in the ghrelin and leptin genes and their association with eating behavior. The understanding of these mechanisms is relevant since it could impact on the objectives of pharmacological or behavioral interventions for their treatment.

The role of ghrelin and leptin in feeding behavior: Genetic and molecular evidence. / Papel de la grelina y la leptina en el comportamiento alimentario: evidencias genéticas y moleculares.

Feeding behavior is integrated within a wide variety of eating behaviors, which depend on psychosocial, biological and environmental factors. These types of behavior can cause nutrition-related diseases such as obesity, which affects more than 650 million people worldwide. Ghrelin and leptin are key hormones that regulate appetite, food intake and energy metabolism. Research in genetics suggests that genetic variants of both hormones are associated with complex forms of eating behavior, such as a preference for palatable food, making individuals susceptible to the modern obesogenic environment. This review analyses the scientific evidence around polymorphisms in the ghrelin and leptin genes and their association with eating behavior. The understanding of these mechanisms is relevant since it could impact on the objectives of pharmacological or behavioral interventions for their treatment.

Anthropometric measure and adipokine levels of a young undergraduate population with a usual diet.

INTRODUCTION: Background: the aim of this study was to evaluate the intake of nutrients, anthropometric parameters, health indicators, adipokines and insulin levels in a population of young undergraduates. Method: in this study, 378 young undergraduates were invited to participate. Due to the inclusion criteria and their own decision of participating, 90 attended the anthropometric, health indicators: waist circumference (WC), waist to hip ratio (WHR), waist to height ratio (WHtR), and homeostatic model assessment-insulin resistance index (HOMA-IR) studies and completed the questionnaire of frequency of food intake; and 34 participants were selected to perform the determination of biochemical parameters, insulin and adipokines levels: leptin, IL-6, IL-8, tumor necrosis factor alpha (TNF-α), monocyte chemoattractant protein-1 (MCP-1) and hepatocyte growth factor (HGF). Results: according to WC, WHR and WHtR, obese population showed health, cardiovascular and metabolic risk. Overweight population showed cardiometabolic risk. In general, lipid intake was higher than 30%, being animal fat the most consumed. The levels of leptin (women: 17.2 ± 9.2, 28 ± 11.3, 36.8 ± 17.8; men: 4.3 ± 3.6, 9.5 ± 3.1, 24.6 ± 16.4 to lean overweight and obese, respectively) and insulin (women: 408 ± 182, 438 ± 187, 768 ± 167; men: 244 ± 88, 520 ± 256, 853 ± 590) increased along with body mass index (BMI), body fat percentage (BFP), visceral fat area (VFA), WC, WHR and WHtR. Lean (2.4 ± 1.3), overweight (2.2 ± 0.9) and obese (4.3 ± 1.1) women and overweight (2.8 ± 1.2) and obese (5.0 ± 3.1) men showed insulin resistance according to HOMA-IR. Significant correlation between leptin and HOMA-IR was found (p = 0.41). BMI, BFP, VFA, WC, and WHtR positively correlated with leptin (p = 0.67, 0.75, 0.66, 0.60, 0.67, respectively) and insulin (p = 0.37, 0.40, 0.48, 0.49, 0.42, respectively), while WHR only with insulin (p = 0.43). No significant differences were found in the other adipokines. Conclusion: the use of health indicators such VFA, WC, WHR, WHtR and HOMA-IR are useful tools in the determination of health, cardio vascular and metabolic risk and are correlated with levels of leptin and insulin in the studied population.

INTRODUCCIÓN: Introducción: el objetivo de este estudio fue evaluar la ingesta de nutrientes, parámetros antropométricos, indicadores de salud, adipocinas y niveles de insulina en una población de jóvenes universitarios con una dieta habitual. Método: en este estudio se invitó a participar a 378 jóvenes universitarios. Debido a los criterios de inclusión y su propia decisión de participar, 90 asistieron a los estudios antropométricos y de indicadores de salud: circunferencia de cintura (WC), índice de cadera cintura (WHR), índice de cintura-talla (WHtR) y modelo homeostático de evaluación-índice de resistencia a la insulina (HOMA-IR) y completaron el cuestionario de frecuencia de ingesta de alimentos. Treinta y cuatro participantes fueron seleccionados para realizar la determinación de los parámetros bioquímicos, niveles de insulina y adipocinas (leptina, IL-6, IL-8, factor de necrosis tumoral alfa [TNF-α], proteína quimioatractante de monocitos-1 [MCP-1] y factor de crecimiento hepático [HGF]). Resultados: de acuerdo con WC, WHR y WHtR, la población obesa mostró riesgo cardiovascular, metabólico y para la salud. La población con sobrepeso mostró riesgo cardiometabólico. En general, la ingesta de lípidos fue superior al 30% y la grasa animal fue la más consumida. Los niveles de leptina (mujeres: 17,2 ± 9,2, 28 ± 11,3, 36,8 ± 17,8; hombres: 4,3 ± 3,6, 9,5 ± 3,1, 24,6 ± 16,4 para delgados, sobrepeso y obesos, respectivamente) e insulina (mujeres: 408 ± 182, 438 ± 187, 768 ± 167; hombres: 244 ± 88, 520 ± 256, 853 ± 590) aumentaron junto con el índice de masa corporal (BMI), porcentaje de grasa corporal (BFP), área de grasa visceral (VFA), WC, WHR y WHtR. Las mujeres delgadas (2,4 ± 1,3), con sobrepeso (2,2 ± 0,9) y obesas (4,3 ± 1,1) y los hombres con sobrepeso (2,8 ± 1,2) y obesos (5,0 ± 3,1) mostraron resistencia a la insulina de acuerdo con HOMA-IR. Se encontró una correlación significativa entre leptina y HOMA-IR (p = 0,41). BMI, BFP, VFA, WC y WHtR correlacionaron positivamente con leptina (p = 0,67, 0,75, 0,66, 0,60 y 0,67, respectivamente) e insulina (p = 0,37, 0,40, 0,48, 0,49 y 0,42, respectivamente), mientras que el WHR solo con insulina (p = 0,43). No se encontraron diferencias significativas en las otras adipocinas. Conclusión: el uso de indicadores de salud como VFA, WC, WHR, WHtR y HOMA-IR es una herramienta útil en la determinación del riesgo metabólico, cardiovascular y de salud, y dichos indicadores correlacionaron con los niveles de leptina e insulina en la población estudiada.

Concentration of ghrelin and leptin in serum and human milk in nursing mothers according to the type of feeding.

INTRODUCTION: Objective: we assessed the relationship between serum and human foremilk and hindmilk concentrations of ghrelin and leptin in nursing mothers according to the type of feeding. Methods: this cohort design was carried out on 131 mother-newborn dyads admitted to a physiological puerperium ward. The independent variables were the type of feeding, full breastfeeding (FBF, 56.5%) and partial breastfeeding (PBF, 43.5%). The dependent variables were the concentration of total ghrelin (pg/ml) and leptin (ng/ml) in serum, foremilk and hindmilk at eight and 16 weeks. Fasting blood samples were obtained from the nursing mothers at four months for serum assays. Unpaired Student's t-test, Mann-Whitney U test, Pearson's correlation tests, coefficient of determination and linear regression were used. Results: the concentration of ghrelin and leptin in hindmilk was higher than that of foremilk in both groups at eight and 16 weeks. The concentration of ghrelin and leptin was higher in serum than in foremilk in both groups. These values showed a direct and significant linear correlation with the exception of ghrelin in the FBF group. The serum concentration of leptin in mothers explained 32% of the variance of its concentration in foremilk in the FBF and 13% in the PBF groups. Conclusion: the hindmilk/foremilk gradient suggests an intake regulating mechanism during the fed. The concentration of ghrelin and leptin was higher in the serum than in foremilk and its correlation and determination coefficients could suggest plasma-milk transfer in addition to synthesis regulation by the mammary gland, adipose tissue or other organs.

INTRODUCCIÓN: Objetivo: evaluar la relación entre la concentración de suero y la leche materna y la concentración de grelina y leptina en leche materna en madres lactantes según el tipo de alimentación. Métodos: diseño de cohorte realizado en 131 diadas madre-lactante que ingresaron en una sala de puerperio fisiológico. Variables independientes: tipo de alimentación, lactancia materna completa (LMC, 56,5%) y lactancia materna parcial (LMP, 43,5%). Variables dependientes: concentración sérica de grelina total (pg/ml) y leptina (ng/ml), leche humana pre-tetada y pos-tetada a las ocho y 16 semanas. Se utilizaron pruebas no pareadas t de Student, U de Mann-Whitney, correlación de Pearson, coeficiente de determinación y regresión linear. Resultados: la concentración de grelina y leptina en leche humana pre-tetada fue mayor que en leche humana pos-tetada en ambos grupos a las ocho y 16 semanas. La concentración de grelina y leptina fue mayor en suero que en leche humana en ambos grupos; estos valores mostraron una correlación lineal directa y significativa con la excepción de la grelina en el grupo de LMC. La concentración sérica de leptina en las madres explicó el 32% de la varianza de su concentración en leche humana en LMC y el 13% en madres en LMP. Conclusión: el gradiente de leche humana pre-tetada/pos-tetada sugiere un mecanismo de regulación e ingestión de leche. La concentración de grelina y leptina fue mayor en suero que en leche humana y los coeficientes de determinación sugieren una transferencia de suero-leche, además de una regulación de la síntesis por la glándula mamaria, el tejido adiposo u otros órganos.

Status de expressão do receptor de leptina e adiponectina no carcinoma colorretal: A cross-estudo prospectivo seccional / Correlation of leptin and adiponectin receptor expression with clinicopathological parameters in colorectal carcinoma - a cross-sectional prospective study

ABSTRACT Background: Colorectal carcinoma (CRC) is one of the common carcinomas with a rising incidence of metastasis due to its advanced stage of presentation. The existing biomarkers such as CEA (Carcinoembryonic antigen) etc., for prognosis, have low sensitivity and specificity. Hence a need for a newer definitive biomarker. Obesity is the leading cause of CRC. Leptin and adiponectin secreted by adipose tissue have been studied as potential biomarkers in the field of CRC. The present study helps to understand the association of leptin and adiponectin receptors with clinicopathological parameters. Objective: To correlate the various clinicopathological parameters with the tissue expression of leptin and adiponectin receptors in CRC. Methods: It is a cross-sectional prospective study conducted at a tertiary care hospital. Formalin fixed paraffin blocks of all radical resection CRC cases were collected and immunohistochemistry (IHC)was carried out on tumor tissue for leptin and adiponectin receptor. Tumor characteristics and clinical parameters were collected from the hospital medical records. Pearson's correlation coefficient test was used. Results: Immunohistochemistry was performed on 60 cases of CRC. Significant positive correlation of leptin was observed with size, lymph node metastasis, advanced stage, and grade of tumor (P<0.05). A significant correlation between adiponectin receptor and CRC was observed concerning age, stage, lymph node metastasis, distant metastasis and grade of tumor. Conclusion: Positive expression of leptin and negative expression of adiponectin receptors in CRC helps to predict the risk of metastasis.

RESUMO Contexto: O carcinoma colorretal (CCR) é um dos carcinomas comuns com incidência crescente de metástases devido ao seu estágio avançado de apresentação. Os biomarcadores existentes como CEA (antígeno carcinoembrionário) etc., para prognóstico, apresentam baixa sensibilidade e especificidade. Daí a necessidade de um biomarcador definitivo mais recente. A obesidade é a principal causa do CCR. A leptina e a adiponectina secretadas pelo tecido adiposo têm sido estudadas como potenciais biomarcadores na área do CCR. O presente estudo ajuda a compreender a associação dos receptores de leptina e adiponectina com parâmetros clinicopatológicos. Objetivo: Correlacionar os diversos parâmetros clinicopatológicos com a expressão tecidual dos receptores de leptina e adiponectina no CCR. Métodos: Trata-se de um estudo transversal, prospectivo, realizado em um hospital terciário. Blocos de parafina fixados em formalina de todos os casos de CCR de ressecção radical foram coletados e a imuno-histoquímica (IHQ) foi realizada no tecido tumoral para receptor de leptina e adiponectina. As características do tumor e os parâmetros clínicos foram coletados dos prontuários médicos do hospital. Foi utilizado o teste do coeficiente de correlação de Pearson. Resultados: A imunohistoquímica foi realizada em 60 casos de CCR. Correlação positiva significativa da leptina foi observada com tamanho e metástase linfonodal, estágio avançado e grau do tumor (P<0,01). Foi observada uma correlação significativa entre o receptor de adiponectina e o CCR em relação à idade, estágio, metástase linfonodal, metástase à distância e grau do tumor. Conclusão: A expressão positiva de leptina e a expressão negativa de receptores de adiponectina no CCR ajudam a prever o risco de metástase.

Legume consumption increase adiponectin concentrations among type 2 diabetic patients: A randomized crossover clinical trial.

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.

Circulating leptin levels in the assessment of Crohn’s disease activity and its relation to nutritional status / Los niveles circulantes de leptina en la evaluación de la actividad de la enfermedad de Crohn y su relación con el estado nutricional

Objective: to evaluate leptin levels and its relation to nutritional status in Crohn’s disease (CD).Methods: the study included 154 CD patients and healthy controls. Leptin level was determined before treatment. Nutrition levels were assessedusing the Nutrition Risk Screening 2002 (NRS-2002) and Patient-Generated Subjective Global Assessment (PG-SGA). Indicators included bodymass index (BMI), mid-arm circumference, the circumference of the upper-arm muscle, triceps skinfold thickness, and circumference of legs.Results: leptin levels differed between CD patients (1,025 ± 874 ng/ml) and controls (18,48 ± 1,222 ng/ml). Significant differences were seenin NRS-2002, PG-SGA scores, BMI and other nutritional indicators. Negative correlations were observed between leptin and NRS-2002, PG-SGAscores, while positive correlations were observed with other nutritional indicators. The receiver operating characteristic (ROC) curve showedassociation between leptin and the diagnosis of CD, suggesting leptin concentration below 803.02 ng/ml as a threshold for CD.Conclusion: dysfunctional leptin regulation may relate to poor nutritional status associated with CD. The leptin level is thus an additional toolfor evaluating CD patients, predicting disease activity and clinical response. Leptin may be a potential target for intervention in CD to improvenutritional status.(AU)

Objetivo: evaluar los niveles de leptina y su relación con el estado nutricional en la enfermedad de Crohn (EC).Métodos: se incluyeron 154 pacientes con EC y controles sanos. El nivel de leptina se determinó antes del tratamiento. La situación nutricionalse evaluó mediante el examen de riesgo nutricional 2002 (NRS-2002) y la Valoración Global Subjetiva Generada por el Paciente (VGS-GP). Losindicadores incluyen el índice de masa corporal (IMC), la circunferencia media del brazo, la circunferencia del músculo superior del brazo, elgrosor del pliegue cutáneo del tríceps y la circunferencia de las piernas.Resultados: los niveles de leptina difirieron entre los pacientes con EC (1.025 ± 874 ng/ml) y los controles (18.48 ± 1.222 ng/ml). Se obser-varon diferencias significativas en NRS-2002, puntajes de VGS-GP, IMC y otros indicadores nutricionales. Se observaron correlaciones negativasentre leptina y NRS-2002, puntuaciones de VGS-GP, mientras que se observaron correlaciones positivas con otros indicadores nutricionales.La curva ROC mostró asociación entre leptina y el diagnóstico de EC, sugiriendo concentraciones de leptina por debajo de 803,02 ng/ml comoumbral para EC.Conclusión: puede relacionarse la alteración en la regulación de la leptina con la peor situación nutricional en enfermos con EC. La leptinapuede ser un objetivo potencial para la intervención en EC a fin de mejorar el estado nutricional.(AU)

Leptina, obesidad y enfermedades cardiovasculares / Leptin, obesity and cardiovascular diseases

Introducción: la obesidad está asociada con el síndrome metabólico, la hipertensión, la aterosclerosis y las enfermedades del corazón. El tejido adiposo funciona como un órgano endocrino al secretar múltiples proteínas inmunomoduladoras conocidas como adipocinas, que pueden actuar en forma directa sobre órganos cercanos o remotos. Objetivos: la búsqueda de las funciones de las diferentes adipocinas ha permitido establecer la relación entre obesidad y enfermedades cardiovasculares. La primera conduce a mayor expresión de algunas adipocinas proinamatorias y disminución de otras antiinamatorias, dando como resultado el desarrollo de un estado inamatorio crónico de bajo grado. Discusión: algunas adipocinas disminuyen su expresión en sujetos obesos. Sin embargo, la leptina la aumenta en obesidad y promueve complicaciones relacionadas con esta. Conclusiones: estudios clínicos y experimentales indican que la leptina contribuye al desarrollo de cardiopatía isquémica y ejerce acciones perniciosas en las enfermedades cardiovasculares relacionadas con la obesidad.

Introduction: obesity is associated with metabolic syndrome, hypertension, atherosclerosis and heart disease. Adipose tissue functions as an endocrine organ by secreting multiple immune-modulatory proteins known as adipokines, that can directly act on nearby or remote organs. Objetive: research on the various functions of adipokines has shed light on the relationship between obesity and cardiovascular diseases. Obesity leads to increased expression of some pro-inammatory adipokines and diminished expression of other anti-inammatory adipokines, resulting in the development of a chronic low-grade inammatory state. Some adipokines decrease their expression in obese individuals. However, obese subjects have elevated leptin levels which promote obesity-related complications. Conclusions: clinical and experimental studies indicate that leptin contributes to the development of ischemic heart disease and exerts pernicious actions on obesity-linked cardiovascular diseases.

Correlación entre Leptina, indicadores antropométricos y parámetros metabólicos en paciente de 5-15 años con sobrepeso-obesidad

Introducción: la obesidad es un estado patológico caracterizado por una acumulación excesiva de tejido adiposo, la misma secreta adipocinas entre las cuales se encuentra la Leptina que está implicada en importantes funciones metabólicas como el control de apetito y peso corporal. Objetivos: se realizo este estudio de la correlación entre la concentración de Leptina sérica con indicadores antropométricos y parámetros bioquímicos en pacientes entre 5 a 15 años de edad, con sobrepeso u obesidad. Métodos: se efectuó e estudio observacional descriptivo de corte transversal, con 148 pacientes entre 5 y 15 años de edad, se realizaron exámenes bioquímicos para evaluar la concentración de Leptina, Glucosa, Insulina, perfil lipídico e indicadores antropométricos. IMC, %GC y RCE. Resultados Se determinó correlaciones positivas entre las concentraciones de Leptina sérica con el IMC (75,4; p< 0,000), el (% GC) Porcentaje de grasa corporal (70,7: p< 0,000) y el (RCE) Razón Cintura estatura (75,4; p< 0,000), encontramos que no existe correlación entre la concentración de Leptina y Colesterol Total, por otra parte encontramos correlación negativa inversa con la concentración de Colesterol HDL en el sexo masculino, mientras que los Triglicéridos presentaron una correlación estadísticamente significativa. Por otra parte, no encontramos correlación significativa entre la determinación de la Leptina y la glicemia, por el contrario, la insulina presento una correlación alta estadísticamente significativa (p<0,000). Conclusiones: este estudio muestra la existencia de correlación estadísticamente significativa entre la Leptina sérica con indicadores antropométricos y parámetros bioquímicos en pacientes entre 5 a 15 años de edad, que tienen sobrepeso u obesidad.

Introduction: Obesity is a pathological state characterized by an excessive accumulation of adipose tissue, which secretes adipokines where there is Leptin, that is involved in important metabolic functions such as appetite control and body weight. Objectives: a study was carried out on the correlation between the serum Leptin concentration with anthropometric indicators and biochemical parameters in patients between 5 and 15 years old, overweight and obesity. Methods: the cross-sectional descriptive observational study was carried out, with 148 patients between 5 and 15 years of age, biochemical tests were performed to evaluate the concentration of Leptin Glucose, insulin, lipid profile and anthropometric indicators BMI, % BF y WHR. Results: positive correlations were found between serum Leptin concentrations with BMI (75.4; p <0.000), the (% BF) Body fat percentage (70.7: p <0.000) and the (WHR) Waist Ratio height (75,4 p <0.000). A low correlation was observed between the Leptin concentration and Total Cholesterol, with the concentration of HDL Cholesterol an inverse correlation was found in male sex, while Triglycerides presented higher levels in the adolescent group, there was no statistically significant. Also, we did not find a significant between the determination of Leptin and glycemia, on the contrary, insulin presented a statistically significant higher correlation (p <0.000). Conclusion: this study shows the existence of a statistically significant correlation between serum Leptin with anthropometric indicators and biochemical parameters in patients between 5 and 15 years of age, who are overweight or obese.