RESUMO
The ovine choroid plexus (ChP) expresses the long isoform of the leptin receptor, which makes this structure a potential target for leptin action. In sheep, leptin concentration in plasma is higher during long days (LD) than short days (SD). This study evaluates the influence a of photoperiod on leptin impact on the gene expression of Toll-like receptor 4 (TLR4), proinflammatory cytokines (IL1B, IL6), their receptors (IL1R1, IL1R2, ILRN, IL6R, IL6ST) and inflammasome components necessary for pro-IL-1ß activation (NLRP3, PYCARD, CASP1), chemokine (CCL2), leptin receptor isoforms (LEPRa, LEPRb) and a suppressor of cytokine signalling (SOCS3) in the ChP of ewes treated or not with lipopolysaccharide (LPS). Studies were conducted on adult female sheep divided into four groups (n = 6 in each): control, leptin (20 µg/kg), LPS (400 ng/kg), and LPS and leptin injected under SD and LD photoperiods. The leptin alone did not affect the gene expression but in co-treatment with LPS increased (p < 0.05) IL1B but only during SD, and SOCS3, IL1R2, IL1RN, IL6ST and CCL2 only during LD, and decreased (p < 0.05) the IL1R1 expression only during SD photoperiod. This indicates that the immunomodulatory action of leptin on the ChP is manifested only under the LPS challenge and is photoperiodically dependent.
Assuntos
Plexo Corióideo/metabolismo , Inflamassomos/metabolismo , Leptina/sangue , Fotoperíodo , Animais , Quimiocina CCL2/genética , Quimiocina CCL2/metabolismo , Plexo Corióideo/efeitos dos fármacos , Feminino , Inflamassomos/genética , Interleucina-1beta/genética , Interleucina-1beta/metabolismo , Interleucina-6/genética , Interleucina-6/metabolismo , Lipopolissacarídeos/toxicidade , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Receptores de Interleucina/genética , Receptores de Interleucina/metabolismo , Receptores para Leptina/genética , Receptores para Leptina/metabolismo , Ovinos , Receptor 4 Toll-Like/genética , Receptor 4 Toll-Like/metabolismoRESUMO
Alterations in birth weight impact postnatal outcome and adult metabolic health. Therefore, fetal growth regulation is crucial for preventing chronic metabolic diseases. Leptin has been suggested to play an important role in placental and fetal growth, albeit its specific mechanisms of action have not been elucidated. The aim of this study was to analyze leptin concentrations in placenta, cord blood, and maternal blood of SGA, AGA, and LGA (small, adequate and large for gestational age, respectively) newborns, as well as placental leptin receptor (LEPRa and LEPRb) protein expression. We performed a cross-sectional comparative study in 3 groups of healthy mothers and their term newborns at delivery (SGA, AGA, and LGA, n=20 per group). Placental, maternal blood, and cord blood leptin content were measured by ELISA. Placental LEPRa and LEPRb protein expression were determined by Western Blot. Maternal leptin concentrations correlated positively with maternal weight before and at the end of gestation, without differences between groups. Cord leptin is higher in LGA and lower in SGA, whereas placental leptin is higher in SGA. Placental leptin was inversely correlated with placental weight, independently from maternal weight and gestational age. Both LEPRa and LEPRb expression are lower in SGA, while LEPRa positively correlated with placental weight and birthweight. The current findings indicate that placental leptin and its receptors are differentially expressed in SGA, AGA, and LGA newborns. We suggest that placental leptin and LEPR protein expression may influence placental growth and thus, birth weight.
Assuntos
Recém-Nascido Pequeno para a Idade Gestacional/sangue , Leptina/sangue , Placenta/metabolismo , Receptores para Leptina/sangue , Adulto , Antropometria , Feminino , Sangue Fetal/metabolismo , Humanos , Recém-Nascido , Tamanho do Órgão , Gravidez , Receptores para Leptina/metabolismoRESUMO
Leptin availability in perinatal life critically affects metabolic programming. We tested the hypothesis that uteroplacental insufficiency and intrauterine stress affect perinatal leptin availability in rat offspring. Pregnant rats underwent bilateral uterine vessel ligation (LIG; n = 14), sham operation (SOP; n = 12), or no operation (controls, n = 14). Fetal livers (n = 180), placentas (n = 180), and maternal blood were obtained 4 hours (gestational day [E] 19), 24 hours (E20), and 72 hours (E22) after surgery. In the offspring, we took blood samples on E22 (n = 44), postnatal day (P) 1 (n = 29), P2 (n = 16), P7 (n = 30), and P12 (n = 30). Circulating leptin (ELISA) was significantly reduced in LIG (E22, P1, P2) and SOP offspring (E22). Postnatal leptin surge was delayed in LIG but was accelerated in SOP offspring. Placental leptin gene expression (quantitative RT-PCR) was reduced in LIG (E19, E20, E22) and SOP (E20, E22). Hepatic leptin receptor (Lepr-a, mediating leptin degradation) gene expression was increased in LIG fetuses (E20, E22) only. Surprisingly, hypoxia-inducible factors (Hif; Western blot) were unaltered in placentas and were reduced in the livers of LIG (Hif1a, E20; Hif2a, E19, E22) and SOP (Hif2a, E19) fetuses. Gene expression of prolyl hydroxylase 3, a factor expressed under hypoxic conditions contributing to Hif degradation, was increased in livers of LIG (E19, E20, E22) and SOP (E19) fetuses and in placentas of LIG and SOP (E19). In summary, reduced placental leptin production, increased fetal leptin degradation, and persistent perinatal hypoleptinemia are present in intrauterine growth restriction offspring, especially after uteroplacental insufficiency, and may contribute to perinatal programming of leptin resistance and adiposity in later life.
Assuntos
Leptina/metabolismo , Placenta/metabolismo , Insuficiência Placentária/metabolismo , Receptores para Leptina/metabolismo , Animais , Fatores de Transcrição Hélice-Alça-Hélice Básicos/metabolismo , Feminino , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Leptina/sangue , Leptina/genética , Fígado/metabolismo , Insuficiência Placentária/sangue , Insuficiência Placentária/genética , Gravidez , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Ratos , Ratos Wistar , Receptores para Leptina/genéticaRESUMO
BACKGROUND: Skin tags (STs), are papillomas commonly found in the neck and in the axillae of middle-aged and elderly people. Metabolic syndrome (MS) is a complex of interrelated risk factors for cardiovascular disease and diabetes. Epidemiologic studies of different ethnic populations have indicated that hyperleptinaemia and leptin resistance are strongly associated with MS. AIM: To study the possible relation of skin tags and leptin levels to MS guided by the International Diabetes Federation (IDF) diagnostic criteria. METHODS: This study included 80 participants, 40 ST patients and 40 apparently healthy controls. Age, sex, waist circumference (WC), body mass index (BMI), smoking status, fasting glucose level, insulin level and insulin resistance were estimated as well as cholesterol, triglycerides, HDL, criteria of MS, and leptin levels. RESULTS: The univariate analysis showed that WC, BMI, fasting glucose, insulin levels, insulin resistance, cholesterol, triglycerides, HDL, and leptin levels were significantly higher in ST patients compared to controls (P<0.001). The multivariate analysis between MS components and ST showed that only high triglyceride levels (OR 1.205/95% CI 1.044-1.391/P=0.011) and low HDL levels (OR 0.554/95% CI 0.384-0.800/P=0.002) were significantly associated with ST. Multivariate linear regression analysis of the predictors of high plasma leptin levels, showed that high triglyceride levels (OR 0.287/95% CI 0.410-3.56/P=0.014), and low HDL levels (OR -0.404/95% CI -8.7 to -2.08/P=0.002) were significant predictors. CONCLUSION: The results of this study suggested that the presence of both ST and hyperleptinaemia in patients with STs may be associated with high levels of triglycerides and low levels of HDL and this could suggest that changing the life style of patients with ST may have a beneficial role.