A Neural Circuit Mechanism Controlling Breathing by Leptin in the Nucleus Tractus Solitarii / 神经科学通报·英文版

Leptin, an adipocyte-derived peptide hormone, has been shown to facilitate breathing. However, the central sites and circuit mechanisms underlying the respiratory effects of leptin remain incompletely understood. The present study aimed to address whether neurons expressing leptin receptor b (LepRb) in the nucleus tractus solitarii (NTS) contribute to respiratory control. Both chemogenetic and optogenetic stimulation of LepRb-expressing NTS (NTSLepRb) neurons notably activated breathing. Moreover, stimulation of NTSLepRb neurons projecting to the lateral parabrachial nucleus (LPBN) not only remarkably increased basal ventilation to a level similar to that of the stimulation of all NTSLepRb neurons, but also activated LPBN neurons projecting to the preBötzinger complex (preBötC). By contrast, ablation of NTSLepRb neurons projecting to the LPBN notably eliminated the enhanced respiratory effect induced by NTSLepRb neuron stimulation. In brainstem slices, bath application of leptin rapidly depolarized the membrane potential, increased the spontaneous firing rate, and accelerated the Ca2+ transients in most NTSLepRb neurons. Therefore, leptin potentiates breathing in the NTS most likely via an NTS-LPBN-preBötC circuit.

Leptin relieves ischemia/reperfusion induced acute kidney injury through inhibiting apoptosis and autophagy / 中南大学学报(医学版)

OBJECTIVES@#Acute kidney injury (AKI) can be caused by ischemia/reperfusion (I/R), nephrotoxin, and sepsis, with poor prognosis and high mortality. Leptin is a protein molecule that regulates the body's energy metabolism and reproductive activities via binding to its specific receptor. Leptin can inhibit cardiomyocyte apoptosis caused by I/R, but its effect on I/R kidney injury and the underlying mechanisms are still unclear. This study aims to investigate the effect and mechanisms of leptin on renal function, renal histopathology, apoptosis, and autophagy during acute I/R kidney injury.@*METHODS@#Healthy adult male mice were randomly divided into 4 groups: a sham+wild-type mice (ob/+) group, a sham+leptin gene-deficient mice (ob/ob) group, an I/R+ob/+ group, and an I/R+ob/ob group (n=8 per group). For sham operation, a longitudinal incision was made on the back of the mice to expose and separate the bilateral kidneys and renal arteries, and no subsequent treatment was performed. I/R treatment was ischemia for 30 min and reperfusion for 48 h. The levels of BUN and SCr were detected to evaluate renal function; HE staining was used to observe the pathological changes of renal tissue; TUNEL staining was used to observe cell apoptosis, and apoptosis-positive cells were counted; Western blotting was used to detect levels of apoptosis-related proteins (caspase 3, caspase 9), autophagy-related proteins [mammalian target of rapamycin (mTOR), phosphorylated mTOR (p-mTOR), LC3 I, LC3 II], mTOR-dependent signaling pathway proteins [phosphate and tension homology (PTEN), adenosine monophosphate-activated protein kinase (AMPK), protein kinase B (AKT), extracellular regulated protein kinase (ERK), phosphorylated PTEN (p-PTEN), phosphorylated AMPK (p-AMPK), phosphorylated AKT (p-AKT), phosphorylated ERK (p-ERK)].@*RESULTS@#There was no significant difference in the levels of BUN and SCr between the sham+ob/+ group and the sham+ob/ob group (both P>0.05). The levels of BUN and SCr in the I/R+ob/+ group were significantly higher than those in the sham+ob/+ group (both P<0.05). Compared with the mice in the sham+ob/ob group or the I/R+ob/+ group, the levels of BUN and SCr in the I/R+ob/ob group were significantly increased (all P<0.05). There was no obvious damage to the renal tubules in the sham+ob/+ group and the sham+ob/ob group. Compared with sham+ob/+ group and sham+ob/ob group, both the I/R+ob/+ group and the I/R+ob/ob group had cell damage such as brush border shedding, vacuolar degeneration, and cast formation. Compared with the I/R+ob/+ group, the renal tubules of the mice in the I/R+ob/ob group were more severely damaged. The pathological score of renal tubular injury showed that the renal tubular injury was the most serious in the I/R+ob/ob group (P<0.05). Compared with the sham+ob/+ group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, the ratio of LC3 II to LC3 I was significantly increased, and the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/+ group (all P<0.05). Compared with the sham+ob/ob group, the protein levels of caspase 3, caspase 9, PTEN, and LC3 II were significantly up-regulated, and the ratio of LC3 II to LC3 I was significantly increased, while the protein levels of p-mTOR, p-PTEN, p-AMPK, p-AKT, and p-ERK were significantly down-regulated in the I/R+ob/ob group (all P<0.05). Compared with the I/R+ob/+ group, the levels of p-mTOR, p-PTEN, p-AMPK, p-AKT were more significantly down-regulated, while the levels of caspase 3, caspase 9, PTEN, and LC3 II were more significantly up-regulated, and the ratio of LC3 II to LC3 I was more significantly increase in the I/R+ob/ob group (all P<0.05).@*CONCLUSIONS@#Renal function and tubular damage, and elevated levels of apoptosis and autophagy are observed in mice kidneys after acute I/R. Leptin might relieve I/R induced AKI by inhibiting apoptosis and autophagy that through a complex network of interactions between mTOR-dependent signaling pathways.

Effects of leptin on proliferation and differentiation of hypoxic rat retinal progenitor cells in vitro / 南方医科大学学报

OBJECTIVE@#To investigate the the effects of leptin on the proliferation, differentiation and PTEN expression of rat retinal progenitor cells (RPCs) cultured under hypoxic condition.@*METHODS@#SD rat RPCs were cultured in normoxic conditions or exposed to hypoxia in the presence of 0, 0.3, 1.0, 3.0, 10, and 30 nmol/L leptin for 12, 48 and 72 h, and the cell viability was assessed using cell counting kit 8 (CCK 8) assay. The RPCs in primary culture were divided into control group, hypoxia group, and hypoxia+leptin group, and after 48 h of culture, the cell medium was replaced with differentiation medium and the cells were further cultured for 6 days. Immunofluorescence staining was employed to detect the cells positive for β-tubulin III and GFAP, and Western blotting was used to examine the expression of PTEN at 48 h of cell culture.@*RESULTS@#The first generation of RPCs showed suspended growth in the medium with abundant and bright cellular plasma and formed mulberry like cell spheres after 2 days of culture. Treatment with low-dose leptin (below 3.0 nmol/L) for 48 h obviously improved the viability of RPCs cultured in hypoxia, while at high concentrations (above 10 nmol/L), leptin significantly suppressed the cell viability (P < 0.05). The cells treated with 3.0 nmol/L leptin for 48 h showed the highest viability (P < 0.05). After treatment with 3.0 nmol/L leptin for 48 h, the cells with hypoxic exposure showed similar GFAP and β-tubulin Ⅲ positivity with the control cells (P>0.05), but exhibited an obvious down-regulation of PTEN protein expression compared with the control cells (P < 0.05).@*CONCLUSION@#In rat RPCs with hypoxic exposure, treatment with low dose leptin can promote the cell proliferation and suppress cellular PTEN protein expression without causing significant effects on cell differentiation.

La leptina promueve la expresión de Hic-5 y la formación de puntos de actina por la vía dependiente de FAK-Src en células epiteliales mamarias MCF10A / Leptin induced Hic-5 expression and actin puncta formation by the FAK/Src-dependent pathway in MCF10A mammary epithelial cells

Resumen Introducción. La leptina es una hormona secretada por los adipocitos que se ha relacionado con el proceso de la transición de epitelio a mesénquima (Epithelial- Mesenchymal Transition, EMT). Promueve la migración e invasión de las células del epitelio mamario mediante la activación de las cinasas FAK y Src, un complejo regulador de vías de señalización que favorecen la expresión de las proteínas relacionadas con la formación de estructuras proteolíticas implicadas en la invasión y progresión del cáncer. Recientemente, se ha descrito que la sobreexpresión y activación de la proteína Hic-5 durante el mencionado proceso de transición, favorece la formación de los puntos de actina (indicativa de la formación y funcionalidad de los invadopodios), lo cual promueve la degradación local de los componentes de la matriz extracelular y la metástasis del cáncer. Objetivos. Evaluar el papel de las cinasas FAK y Src sobre la expresión y localización subcelular de Hic-5 y la formación de puntos de actina inducida por la leptina en la línea celular MCF10A de epitelio mamario no tumoral. Materiales y métodos. Se utilizaron los inhibidores específicos de la FAK (PF-573228) y la Src (PP2) para evaluar el papel de ambas cinasas en los niveles de expresión y localización subcelular de la proteína Hic-5 mediante Western blot e inmunofluorescencia, así como la formación de puntos de actina mediante la tinción con faloidina-TRITC en células MCF10A estimuladas con leptina. Resultados. La leptina indujo el incremento en la expresión de Hic-5 y la formación de puntos de actina. El tratamiento previo con los inhibidores de las cinasas FAK (PF-573228) y Src (PP2), promovió la disminución en la expresión de Hic-5 y de los puntos de actina en la línea celular MCF10A de epitelio mamario no tumoral. Conclusión. La leptina indujo la expresión y la localización perinuclear de Hic-5 y la formación de puntos de actina mediante un mecanismo dependiente de la actividad de las cinasas FAK y Src en las células MCF10A.

Abstract Introduction: Leptin is a hormone secreted by adipocytes that has been associated with the epithelial-mesenchymal transition (EMT). Additionally, leptin promotes the migration and invasion of mammary epithelial cells through the activation of FAK and Src kinases, which are part of a regulatory complex of signaling pathways that promotes the expression of proteins related to the formation of proteolytic structures involved in the invasion and progression of cancer. Recently, overexpression and activation of Hic-5 during the EMT have been shown to induce the formation of actin puncta; these structures are indicative of the formation and functionality of invadopodia, which promote the local degradation of extracellular matrix components and cancer metastasis. Objective: To evaluate the role of FAK and Src kinases in the expression of Hic-5 during the epithelial-mesenchymal transition induced by leptin in MCF10A cells. Materials and methods: We used specific inhibitors of FAK (PF-573228) and Src (PP2) to evaluate Hic-5 expression and subcellular localization by Western blot and immunofluorescence assays and to investigate the formation of actin puncta by epifluorescence in MCF10A cells stimulated with leptin. Results: Leptin induced an increase in Hic-5 expression and the formation of actin puncta. Pretreatment with inhibitors of FAK (PF-573228) and Src (PP2) promoted a decrease in Hic-5 expression and actin puncta formation in the non-tumorigenic mammary epithelial cell line MCF10A. Conclusion: In MCF10A cells, leptin-induced Hic-5 expression and perinuclear localization, as well as the formation of actin puncta through a mechanism dependent on the kinase activity of FAK and Src.

Effect of leptin on in vitro nuclear maturation and apoptosis of buffalo [bubalus bubalis] oocyte

Leptin, as a 16 kDa adipokine, is a pleiotropic cytokine-like hormone that primarily secreted from adipose tissue. It also involves in the regulation of energy homeostasis, neuroendocrine function, immunity, lipid and glucose homeostasis, fatty acid oxidation, angiogenesis, puberty and reproduction. The aim of this study was to investigate the effects of in vitro addition of leptin to in vitro maturation [IVM] medium on buffalo oocyte maturation and apoptosis. In this experimental study, Ovaries from apparently normal reproductive organs of slaughtered adult buffaloes [Bubalus bubalis] with unknown breeding history were collected from Urmia Abattoir, Urmia, Iran, and were transported immediately to the laboratory in a thermos flask containing sterile normal saline with added antibiotics. Oocytes were aspirated from 2-8 mm visible follicles of the ovaries using an 18-G needle attached to a 10 ml syringe. IVM medium included tissue culture medium-199 [TCM-199], 10% fetal bovine serum [FBS], 22 microg/ml sodium pyruvate, 0.5 IU/ml ovine follicle-stimulating hormone [oFSH], 0.5 IU/ml ovine luteinizing hormone [oLH], 1 microg/ml oestradiol, 50 microg/ml gentamycin, and leptin [0 [control], 10, 50, and 100 ng/ml]. The good quality buffalo oocytes [batches of 10 oocytes] were placed in a culture plate containing six 50 microl droplets of maturation medium, covered with sterilized mineral oil, and then incubated at 38.5?C with 5% CO2 in air for 24 hours. The maturation of oocytes was evaluated under a stereomicroscope by detecting the first polar body extrusion of oocytes. FITC-Annexin V - propidium iodide [PI] staining method was used to detect oocyte apoptosis. From a total of 115 collected ovaries, 1100 oocytes were recovered among which 283 oocyte were suitable for IVM. In the groups of leptin treated with 0 [control], 10, 50 and 100 ng/ml, the percentage of oocytes maturation was 74.65, 83.81, 77.85, and 75.40%, while the percentage of oocytes apoptosis was 9.83, 9.54, 9.93, and 10.42%, respectively. Our results showed that addition of 10 ng/ml leptin to buffalo IVM medium increased oocyte maturation, significantly, as compared with that in control group. However, addition of leptin to IVM medium had no significant influence on buffalo oocyte apoptosis. Our findings suggested that addition of 10 ng/ml leptin to IVM medium of buffalo oocyte can improve oocyte nuclear maturation. Furthermore, we showed that there is no relation between in vitro addition of leptin to buffalo oocyte IVM medium and oocyte apoptosis

Human Leptin Protein Induces Proliferation of A549 Cells via Inhibition of PKR-Like ER Kinase and Activating Transcription Factor-6 Mediated Apoptosis

PURPOSE: To investigate the anti-apoptotic mechanism of leptin in non-small cell lung cancer. MATERIALS AND METHODS: The influences of leptin on apoptosis were investigated, analyzing the mechanism that triggers growth of A549 cells. The effects of leptin on cell proliferation were examined by XTT analysis. Leptin, C/EBP homologous protein (CHOP), phosphorylated-PKR-like ER kinase (p-Perk), inositol requiring proteins-1, spliced X-box transcription factor-1 (XBP1), cleaved activating transcription factor-6 (ATF6), eukaryotic translation initiation factor-2alpha, caspase-12 and CHOP protein were detected in four groups by western blot, and endoplasmic reticulum (ER) stress related mRNA were detected by reverse transcription PCR. RESULTS: The expression of leptin in A549 and leptin transfected cells inhibited cisplatin activated ER stress-associated mRNA transcription and protein activation. Two ER stress unfolded protein response pathways, PERK and ATF6, were involved, and XBP1 and tumor necrosis factor receptor-associated factor 2 (TRAF2) were increased significantly when treated with cisplatin in A549-siRNA against leptin cells. Furthermore, CHOP expression was inhibited upon leptin expression in A549, LPT-PeP and LPT-EX cells. CONCLUSION: Leptin serves as an important factor that promotes the growth of A549 cells through blocking ER stress-mediated pathways. This blocking is triggered by p-Perk and ATF6 via inhibition of CHOP expression.

[Effect of insulin and leptin on ram sperm capacitation for in vitro embryo production]

Improvement of sperm quality as a research field in reproductive biotechnology of domestic animal can be considered as a key element for in vitro fertilization. The aim of the present study was to investigate the effects of insulin and leptin on ovine sperm capacitation / acrosomal reaction, viability and fertilization. The semen samples of 10 Bakhtiari rams were collected by artificial vagina. Using dose response study, the most efficient doses of insulin and leptin were chosen. Each sample was assigned to four experimental groups including insulin [1nM], leptin [100nM], mixed of leptin-insulin and control [without hormone]. Sperm capacitation/acrosomal reaction, viability and fertilization were evaluated by chlortetracycline staining, eosin-negrosin and in-vitro fertilization methods, respectively. values were compared among groups by 1-way ANOVA. Values of capacitation/ acrosomal reaction rate showed significant increase in response to insulin and leptin at 30, 60 and 120 min time points. The sperm viability was significantly [p<0.05] increased in response to insulin when compared with the control group at 30 min time point, without any effect in the other time points. On the other hand, insulin and leptin did not show significant effect [p>0.05] on sperm fertilization. This study indicated that insulin and leptin improved ram sperm capacitation / acrosomal reaction and viability while their effects on in vitro embryo production were inconsiderable

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

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

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

Leptina e o controle neuroendócrino do peso corporal / Leptin and the neuroendocrine control body weight

A obesidade nos últimos anos vem sendo tratada como um problema de saúde pública, despertando grande interesse nos profissionais da saúde. Compreender o papel da leptina no controle neuroendócrino da ingestão de nutrientes, do gasto energético, depósito de gorduras e do peso corporal é objetivo de um número crescente de pesquisadores, visto que este é um hormônio com papel relevante na interação entre os adipócitos e os neurônios.Nesta revisão atualizamos aspectos como a estrutura da leptina, local e fatores que influenciam na sua síntese, tecidos que expressam receptores e mecanismos de ação. Enfatizamos a ação da leptina no hipotálamo, sítio em que ocorre o controle da ingestão alimentar, com foco em novas perspectivas de intervenção farmacológica no sentido de favorecer maior equilíbrio entre o metabolismo e a ingestão alimentar.

Burn wound angiogenesis is increased by exogenously administered recombinant leptin in rats

BACKGROUND: Leptin is a potent direct angiogenic factor that stimulates endothelial cell migration and activation in vitro and angiogenesis in vivo. In addition, leptin has been discussed to play an important role in angiogenesis, as it promotes the formation of new blood vessels. PURPOSE: The effect of exogenously administered leptin on the healing process of a full tissue burn wound model. METHODS: Sixty-three Sprague-Dawley male rats were used. Full tissue burn wound was created by electrocautery. The width of the pin was 0.3 cm; its length was 2 cm and was used at the "cut" modulation. Rats were divided into seven groups of nine animals each. Burn wounds were injected with murine recombinant leptin and the rats were sacrificed 3, 7 and 9 days after surgery. Every group had obtained three animals for the three different days of sacrifice. Three different leptin doses of 250 pg/ml, 500 pg/ml and 1000 pg/ml were used in different animal groups (A, B and C). For every one of the three leptin doses used, another animal group was evaluated by using the combined injection of leptin and antileptin (A1, B1, and C1), in order to study the inhibitory effect to the leptin factor. Nine rats were served as controls. These were injected with 0.3 ml water for injection solution and sacrificed at the same time intervals. After sacrifice of the animals, the skin was grossly determined by its appearance, colour and texture. Full thickness burn wounds were dissected for histological examination. A qualitative analysis of angiogenesis in the burn wound was conducted following a standard hematoxylin and eosin stain. The wound tissue samples from each experimental group underwent immunohistochemical evaluation of microvessel density by endothelial cell staining with mouse anti-rat CD 34 monoclonal antibody. RESULTS: The most impressive growth of new blood vessels appeared seven and nine days after treatment with the highest leptin doses. There were no significant...

INTRODUÇÃO: A leptina é um potente fator angiogênico que estimula a migração e a ativação de células endoteliais in vitro e a angiogênese in vivo. Além disso, a leptina tem sido considerada importante na angiogênese pois ela promove a formação de novos vasos sanguíneos. OBJETIVO: Investigar o efeito da leptina administrada por via exógena no processo de cicatrização em um modelo experimental de queimadura. MÉTODOS: Foram utilizados sessenta e três ratos Sprague-Dawley, machos. A lesão de espessura total da queimadura foi realizada por eletrocautério. O dano tecidual foi de 0.3 cm numa extensão de 2 cm tendo sido empregada o módulo de "corte"do eletrocautéio. Os ratos foram distribuídos em sete grupos de nove animais. As lesões por queimadura receberam leptina recombinante. Os animais foram sacrificados 3, 7 e 9 dias após o ato operatório. Obteve-se três animais de cada grupo nos três períodos estipulados. Três diferentes dosagens de leptina: 250 pg/ml, 500 pg/ml e 1000 pg/ml foram aplicados nos três diferentes grupos (A, B e C). Para cada uma das três dosagens de leptina, outro grupo de animais foi avaliado pelo uso de injeção combinada de leptina e antileptina (A1, B1 e C1) no sentido de investigar o efeito inibitório do fator leptina. Nove ratos serviram de controles. Estes foram submetidos à injeção de 0.3 ml de água e sacrificados nos mesmos intervalos de tempo. Após o sacrifício dos animais, o tegumento foi avaliado por sua aparência, cor e textura. Fragmentos das feridas queimadas foram ressecadas para exame histológico. A análise qualitativa de angiogênese, na ferida queimada, seguia o padrão da coloração de hematoxilina e eosina. Cada fragmento de tecido, de cada grupo experimental, foi submetido à avaliação imunohistoquímica da densidade dos microvasos pela coloração da célula endotelial por anti-rato CD 34 anticorpo monoclonal. RESULTADOS: O desenvolvimento de novos vasos sanguíneos foi mais significativo após sete e nove dias...

Hormonal regulation of leptin secretion from isolated adipose tissue of male rats

Leptin, the product of ob gene expression mainly by the white adipose tissue cells, is a plasma protein hormone appears to act as a key signaling factor for regulating body weight participating in regulation of energy homeostasis. The escalating interest in leptin study is due to its intimate relation to the worldwide prevalent problem of obesity which reached epidemic proportion.Now it's confirmed that one of the main mechanisms of obesity is decreased leptin action. Leptin seems to play dual role in human physiology being subjected to dual control [Caro et al, 1996] under chronic conditions of steady state energy balance, leptin is a static index of the amount of fat stored in the adipocytes, while under non steady state of energy balance situations leptin may be actively regulated by hormonal or nutritional changes

Leptina e exercício físico aeróbio: implicações da adiposidade corporal e insulina / Leptin and endurance exercise: implications of adiposity and insulin

Atualmente, a obesidade pode ser classificada como uma pandemia e suas conseqüências vão desde o diabetes mellitus até a doença cardíaca. Tanto fatores genéticos como ambientais contribuem para isso, porém, em humanos, o componente genético ainda é pouco definido. Com a clonagem do gene ob de ratos e do seu receptor, foi descoberta a leptina, o "hormônio da saciedade". A leptina é secretada, principalmente, pelo tecido adiposo e reflete a quantidade de gordura depositada no tecido adiposo de um indivíduo. Entretanto, diversos fatores influenciam sua expressão e síntese, tais como jejum, atividade simpática, exercício físico e alterações no balanço energético. Os efeitos da atividade física aeróbia sobre esse hormônio ainda não estão muito claros, visto que existem muitas contradições na literatura sobre sua possível ação na regulação da leptina. Estudos transversais sugerem que as concentrações plasmáticas de leptina não são alteradas após uma sessão de exercício aeróbio. Entretanto, se o esforço físico for extremo, como em uma ultramaratona, na qual há um balanço energético negativo, induzido pela atividade física extenuante, ocorre diminuição dessas concentrações. Além disso, exercícios de longa duração (> 60 min) parecem estar associados à diminuição tardia das concentrações de leptina, aproximadamente 48h após a atividade, provavelmente em função de um possível desequilíbrio energético. Em relação aos estudos longitudinais, após o treinamento aeróbio, alguns autores não observam alterações na leptina plasmática, outros encontram alterações em função apenas das alterações da adiposidade e, por fim, alguns estudos observam diminuição da concentração plasmática e/ou expressão de leptina, independentemente de alterações da massa gorda. Tal fato sugere que haja outro, ou outros, fatores, além do conteúdo de gordura corporal, que modulam a diminuição das concentrações plasmáticas de leptina após o treinamento aeróbio, sendo a insulina a ...

Obesity currently is qualified as a worldwide health epidemic and its consequences include diabetes mellitus as far as cardiac disease. Genetic and environmental factors contribute to obesity, although the genetic component is still poorly understood in humans. With the cloning of mouse ob gene and its receptor, leptin was discovered, the "satiety hormone". Leptin is expressed and secreted primarily by adipose tissue and is highly correlated to body fat mass. Nevertheless, many factors can regulate leptin synthesis and expression, such as fasting, sympathetic activity, insulin, exercise and changes in energy balance. Aerobic physical activity effects on leptin are still not very clear, seeing that there are contradictory studies about its effects on leptin regulation. Transversal studies suggest that leptin concentrations are not acutely affected after an exercise bout. However, reductions in leptin concentrations are observed following extreme bouts of exercise such as ultramarathons, where the extenuating physical activity induces a deficit in energy balance. Also, long-term (> 60 min) exercise seems to be associated with a delayed reduction in leptin concentrations 48 hr after the exercise bout, possibly due to an energy imbalance. Some longitudinal studies show that aerobic exercise training does not affect leptin levels, others that any changes in leptin levels are due to possible changes in body fat, and, lastly, some studies show a reduction in leptin levels and/or expression independently of any changes in adiposity. That suggests there may be other factors besides adiposity that regulate the reduction in leptin levels after exercise training, being insulin the main candidate for such role. Therefore, this review analyses the main aspects of leptin, its action, function and regulation, its association with insulin, and also the effects of acute and chronic endurance exercise on leptin synthesis and secretion and possible implications ...

Behavioral changes induced by cocaine in mice are modified by a hyperlipidic diet or recombinant leptin

The objective of the present study was to determine if the acute behavioral effects of cocaine acutely administered intraperitoneally (ip) at doses of 5, 10 and 20 mg/kg on white male CF1 mice, 90 days of age, would be influenced by leptin acutely administered ip (at doses of 5, 10 and 20 æg/kg) or by endogenous leptin production enhanced by a high-fat diet. The acute behavioral effects of cocaine were evaluated in open-field, elevated plus-maze and forced swimming tests. Results were compared between a group of 80 mice consuming a balanced diet and a high-fat diet, and a group of 80 mice fed a commercially available rodent chow formula (Ralston Purina) but receiving recombinant leptin (rLeptin) or saline ip. Both the high-fat-fed and rLeptin-treated mice showed decreased locomotion in the open-field test, spent more time in the open arms of the elevated plus-maze and showed less immobility time in the forced swimming test (F(1,68) = 7.834, P = 0.007). There was an interaction between diets and cocaine/saline treatments in locomotion (F(3,34) = 3.751, P = 0.020) and exploration (F(3,34) = 3.581, P = 0.024). These results suggest that anxiolytic effects and increased general activity were induced by leptin in cocaine-treated mice and that low leptin levels are associated with behavioral depression. Chronic changes in diet composition producing high leptin levels or rLeptin treatment may result in an altered response to cocaine in ethologic tests that measure degrees of anxiety and depression, which could be attributed to an antagonistic effect of leptin.