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1.
PLoS One ; 15(8): e0237922, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845924

RESUMO

BACKGROUND: Levels of cortisol, melatonin, ghrelin, and leptin are highly correlated with circadian rhythmicity. The levels of these hormones are affected by sleep, feeding, and general behaviors, and fluctuate with light and dark cycles. During the fasting month of Ramadan, a shift to nighttime eating is expected to affect circadian rhythm hormones and, subsequently, the levels of melatonin, cortisol, ghrelin, and leptin. The present study aimed to examine the effect of diurnal intermittent fasting (DIF) during Ramadan on daytime levels of ghrelin, leptin, melatonin, and cortisol hormones in a group of overweight and obese subjects, and to determine how anthropometric, dietary, and lifestyle changes during the month of Ramadan correlate with these hormonal changes. METHODS: Fifty-seven overweight and obese male (40) and female (17) subjects were enrolled in this study. Anthropometric measurements, dietary intake, sleep duration, and hormonal levels of serum ghrelin, leptin, melatonin, and salivary cortisol were assessed one week before the start of Ramadan fasting and after 28 days of fasting at fixed times of the day (11:00 am-1:00 pm). RESULTS: At the end of Ramadan, serum levels of ghrelin, melatonin, and leptin significantly (P<0.001) decreased, while salivary cortisol did not change compared to the levels assessed in the pre-fasting state. CONCLUSIONS: DIF during Ramadan significantly altered serum levels of ghrelin, melatonin, and serum leptin. Further, male sex and anthropometric variables were the most impacting factors on the tested four hormones. Further studies are needed to assess DIF's impact on the circadian rhythmicity of overweight and obese fasting people.


Assuntos
Ritmo Circadiano/fisiologia , Jejum/sangue , Grelina/sangue , Hidrocortisona/sangue , Melatonina/sangue , Obesidade/sangue , Obesidade/fisiopatologia , Adulto , Dieta , Ingestão de Energia , Feminino , Hemodinâmica , Humanos , Leptina/sangue , Lipídeos/sangue , Masculino , Estudos Prospectivos , Sono/fisiologia
2.
PLoS One ; 15(8): e0237708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817646

RESUMO

Parental high-fat diet (HFD) programs for obesity and hypertension in female offspring in rats, but it is unknown how the pregnancies of these offspring are impacted. Therefore, the hypothesis was tested that parental HFD exaggerates obesity and hypertension during pregnancy of the offspring. Wistar Hannover rat dams (the parental, P generation) were maintained on normal-fat diet (NFD) or HFD from weaning and were kept on respective diets through pregnancy and lactation. Their offspring (the first filial, F1 generation) were weaned onto the same diet as the P generation, or they were changed to the other diet to determine if combined HFD in the P and F1 generations exaggerates body weight and blood pressure levels during pregnancy in these offspring. This diet paradigm resulted in the following groups of pregnant F1 offspring: P-NFD/F1-NFD, P-HFD/F1-NFD, P-NFD/F1-HFD, and P-HFD/F1-HFD. Maternal body and adipose tissue weights were greatest in the P-HFD/F1-HFD group compared to the other 3 groups by the end of pregnancy. Plasma leptin and conscious mean arterial blood pressure were not significantly different between any group, although there was a main effect for increased blood pressure in the F1-HFD groups. Circulating levels of the antihypertensive pregnancy factor, placental growth factor (PlGF), were assessed. Although average PlGF levels were similar among all groups, correlative studies revealed that lower levels of PlGF were associated with higher blood pressure only in the P-HFD/F1-HFD group. In summary, HFD feeding from the P generation exaggerated HFD-induced body and adipose tissue weights in the pregnant offspring.


Assuntos
Hipertensão/sangue , Leptina/sangue , Obesidade/sangue , Fator de Crescimento Placentário/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Adiposidade/genética , Animais , Pressão Sanguínea/genética , Peso Corporal/genética , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Herança Materna/genética , Obesidade/genética , Obesidade/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Desmame
3.
Toxicol Lett ; 332: 42-55, 2020 Oct 10.
Artigo em Inglês | MEDLINE | ID: mdl-32629074

RESUMO

Obesity is associated with several female reproductive complications, such as polycystic ovary syndrome (PCOS). The exact mechanism of this relationship remains unclear. Few previous studies using diet containing refined carbohydrate (HCD) leading to obesity have been performed and it is unclear if HCD is linked with reproductive dysfunctions. In this investigation, we assessed whether subchronic HCD exposure results in reproductive and other irregularities. Female rats were fed with HCD for 15 days and metabolic outcomes and reproductive tract morphophysiology were assessed. We further assessed reproductive tract inflammation, oxidative stress (OS) and fibrosis. HCD rats displayed metabolic impairments, such as an increase in body weight/adiposity, adipocyte hypertrophic, abnormal lipid profile, glucose tolerance and insulin resistance (IR) and hyperleptinemia. Improper functioning of the HCD reproductive tract was observed. Specifically, irregular estrous cyclicity, high LH levels and abnormal ovarian morphology coupled with reduction in primordial and primary follicle numbers was observed, suggesting ovarian reserve depletion. Improper follicular development and a reduction in antral follicles, corpora lutea and granulosa layer area together with an increase in cystic follicles were apparent. Uterine atrophy and reduction in endometrial gland (GE) number was observed in HCD rats. Reproductive tract inflammation, OS and fibrosis were seen in HCD rats. Further, strong positive correlations were observed between body weight/adiposity and IR with estrous cycle length, cystic follicles, ovarian reserve, GE and other abnormalities. Thus, these data suggest that the subchronic HCD exposure led to PCOS-like features, impaired ovarian reserve, GE number, and other reproductive abnormalities in female rats.


Assuntos
Carboidratos da Dieta/toxicidade , Reserva Ovariana/efeitos dos fármacos , Ovário/metabolismo , Síndrome do Ovário Policístico/induzido quimicamente , Adiposidade/efeitos dos fármacos , Animais , Peso Corporal , Dieta , Ciclo Estral/efeitos dos fármacos , Feminino , Fibrose , Intolerância à Glucose/sangue , Intolerância à Glucose/induzido quimicamente , Resistência à Insulina , Leptina/sangue , Metabolismo dos Lipídeos , Folículo Ovariano/efeitos dos fármacos , Ovário/patologia , Estresse Oxidativo , Síndrome do Ovário Policístico/metabolismo , Síndrome do Ovário Policístico/patologia , Ratos , Ratos Wistar
4.
Int J Obes (Lond) ; 44(9): 1810-1817, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32647360

RESUMO

Overweight and obesity are major risk factors for diabetes, cardiovascular disease, and lung disease. These diseases are the most commonly reported health conditions that predispose individuals with SARS-CoV-2 infection to require hospitalization including intensive care unit admissions. The innate immune response is the host's first line of defense against a human coronavirus infection. However, most coronaviruses are armed with one strategy or another to overcome host antiviral defense, and the pathogenicity of the virus is related to its capacity to suppress host immunity. The multifaceted nature of obesity including its effects on immunity can fundamentally alter the pathogenesis of acute respiratory distress syndrome and pneumonia, which are the major causes of death due to SARS-CoV-2 infection. Elevated circulating leptin concentrations are a hallmark of obesity, which is associated with a leptin-resistant state. Leptin is secreted by adipocytes in proportion to body fat and regulates appetite and metabolism through signaling in the hypothalamus. However, leptin also signals through the Jak/STAT and Akt pathways, among others, to modulate T cell number and function. Thus, leptin connects metabolism with the immune response. Therefore, it seems appropriate that its dysregulation would have serious consequences during an infection. We propose that leptin may be the link between obesity and its high prevalence as a comorbidity of the SARS-CoV-2 infection. In this article, we present a synthesis of the mechanisms underpinning susceptibility to respiratory viral infections and the contribution of the immunomodulatory effects of obesity to the outcome.


Assuntos
Infecções por Coronavirus , Leptina , Obesidade , Pandemias , Pneumonia Viral , Betacoronavirus , Comorbidade , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Interações Hospedeiro-Patógeno/imunologia , Humanos , Leptina/sangue , Leptina/imunologia , Leptina/metabolismo , Obesidade/epidemiologia , Obesidade/imunologia , Obesidade/metabolismo , Pneumonia Viral/epidemiologia , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Transdução de Sinais/imunologia
5.
Nature ; 583(7817): 620-624, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32669709

RESUMO

Approximately 75% of all breast cancers express the oestrogen and/or progesterone receptors. Endocrine therapy is usually effective in these hormone-receptor-positive tumours, but primary and acquired resistance limits its long-term benefit1,2. Here we show that in mouse models of hormone-receptor-positive breast cancer, periodic fasting or a fasting-mimicking diet3-5 enhances the activity of the endocrine therapeutics tamoxifen and fulvestrant by lowering circulating IGF1, insulin and leptin and by inhibiting AKT-mTOR signalling via upregulation of EGR1 and PTEN. When fulvestrant is combined with palbociclib (a cyclin-dependent kinase 4/6 inhibitor), adding periodic cycles of a fasting-mimicking diet promotes long-lasting tumour regression and reverts acquired resistance to drug treatment. Moreover, both fasting and a fasting-mimicking diet prevent tamoxifen-induced endometrial hyperplasia. In patients with hormone-receptor-positive breast cancer receiving oestrogen therapy, cycles of a fasting-mimicking diet cause metabolic changes analogous to those observed in mice, including reduced levels of insulin, leptin and IGF1, with the last two remaining low for extended periods. In mice, these long-lasting effects are associated with long-term anti-cancer activity. These results support further clinical studies of a fasting-mimicking diet as an adjuvant to oestrogen therapy in hormone-receptor-positive breast cancer.


Assuntos
Neoplasias da Mama/dietoterapia , Neoplasias da Mama/tratamento farmacológico , Dietoterapia/métodos , Jejum/fisiologia , Fulvestranto/uso terapêutico , Animais , Fatores Biológicos/sangue , Neoplasias da Mama/patologia , Dieta Saudável/métodos , Modelos Animais de Doenças , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Proteína 1 de Resposta de Crescimento Precoce/metabolismo , Feminino , Fulvestranto/administração & dosagem , Humanos , Insulina/sangue , Fator de Crescimento Insulin-Like I/metabolismo , Leptina/sangue , Células MCF-7 , Camundongos Endogâmicos NOD , Camundongos SCID , PTEN Fosfo-Hidrolase/metabolismo , Piperazinas/administração & dosagem , Piperazinas/uso terapêutico , Piridinas/administração & dosagem , Piridinas/uso terapêutico , Receptores Estrogênicos , Receptores de Progesterona , Tamoxifeno/efeitos adversos , Tamoxifeno/uso terapêutico , Ensaios Antitumorais Modelo de Xenoenxerto
6.
High Blood Press Cardiovasc Prev ; 27(5): 379-388, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32705504

RESUMO

INTRODUCTION: Structural and functional properties of the left ventricle (LV) wall have been reported to be altered in hypertension, even at early stages of the disease. Abnormal adipokine levels affect blood pressure regulation. Hypo-adiponectinaemia and hyper-leptinaemia were reported in hypertension. AIM: To evaluate the effects of valsartan versus amlodipine on LV deformation also, on plasma adiponectin and leptin levels in hypertensive individuals. METHODS: LV strain was measured by two-dimensional speckle tracking echocardiography, plasma levels of adiponectin and leptin was determined in 30 healthy individuals served as control group and in 200 hypertensive patients before and after treatment for 6 months with either valsartan 160 mg or amlodipine 10 mg. RESULTS: Compared to control group longitudinal strain was significantly affected in hypertensive patients, adiponectin was significantly lower while TNF-α, hs-CRP and leptin levels were significantly higher in hypertensive group. A significant improvement in LV functions, along with a decrease in leptin and increase in adiponectin levels in valsartan group compared to amlodipine group. CONCLUSIONS: Our results indicate that valsartan is superior to amlodipine when it comes to affecting the hormonal function of human adipose tissue. Valsartan has a beneficial effect on LV deformation and function presented in GLS.


Assuntos
Adipocinas/sangue , Anlodipino/uso terapêutico , Bloqueadores do Receptor Tipo 1 de Angiotensina II/uso terapêutico , Anti-Hipertensivos/uso terapêutico , Bloqueadores dos Canais de Cálcio/uso terapêutico , Ecocardiografia , Hipertensão/terapia , Valsartana/uso terapêutico , Função Ventricular Esquerda/efeitos dos fármacos , Remodelação Ventricular/efeitos dos fármacos , Adiponectina/sangue , Adulto , Anlodipino/efeitos adversos , Bloqueadores do Receptor Tipo 1 de Angiotensina II/efeitos adversos , Anti-Hipertensivos/efeitos adversos , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Bloqueadores dos Canais de Cálcio/efeitos adversos , Egito , Feminino , Humanos , Hipertensão/sangue , Hipertensão/diagnóstico por imagem , Hipertensão/fisiopatologia , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Fatores de Tempo , Resultado do Tratamento , Fator de Necrose Tumoral alfa/sangue , Valsartana/efeitos adversos
7.
PLoS One ; 15(6): e0234465, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32544194

RESUMO

Obesity leads a crucial importance in metabolic disorders, as well as type 2 diabetes mellitus. Our present study was designed to assess the potential role of irisin, adiponectin, leptin and gene polymorphism of PNPLA3, leptin and adiponectin as predictive markers of diabetes associated with obesity. One hundred eighty subjects were distributed to three groups including; healthy non-diabetic non obese volunteers as a control group, diabetic non obese group, and diabetic obese group (n = 60 for each group). Fasting blood samples of all groups were collected to determine fasting blood glucose, insulin levels, insulin resistance, total cholesterol, high density lipoprotein cholesterol (HDL-C), low density lipoprotein cholesterol (LDL-C), triacylglycerol, irisin, adiponectin, leptin; as well as, polymorphism of PNPLA3, adiponectin and leptin. The results showed that glucose, insulin resistance, total cholesterol, irisin, leptin, LDL-C, triacylglycerol concentrations were significantly increased, however, insulin, HDL-C, adiponectin were significantly decreased in diabetic obese patients in relation to diabetic non-obese patients as well as in healthy volunteers. The polymorphism of PNPLA3 rs738409 was linearly related to irisin and leptin but was not related with circulating concentrations of adiponectin. We concluded that increased irisin and leptin levels can predict the insulin resistance in obese patients. Moreover, patients who have mutant genotype of PNPLA3 I148 gene (rs738409) C>G, ADIPOQ gene (rs266729) G>C and LEP gene (rs2167270) G>A showed a significant higher susceptibility rate for DM in obese people than those with wild type. This could be considered as an adjustable retort to counter the impact of obesity on glucose homeostasis.


Assuntos
Adiponectina/genética , Diabetes Mellitus Tipo 2/etiologia , Predisposição Genética para Doença , Resistência à Insulina/genética , Leptina/genética , Lipase/genética , Proteínas de Membrana/genética , Obesidade/complicações , Obesidade/genética , Adiponectina/sangue , Adulto , Feminino , Fibronectinas/sangue , Fibronectinas/genética , Marcadores Genéticos , Humanos , Leptina/sangue , Lipase/sangue , Masculino , Proteínas de Membrana/sangue , Polimorfismo Genético , Adulto Jovem
8.
Arch Endocrinol Metab ; 64(3): 276-281, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32555994

RESUMO

OBJECTIVE: Climacterium is associated with elevated leptin levels and increased risk of cardiovascular disorders. Conflicting data diverge on whether high leptin levels in climacterium reflect increasing adipose mass or, at least partially, age-related hormonal changes. This study addresses this issue in women from a Brazilian state with a low human development index. SUBJECTS AND METHODS: A case-control study was conducted, enrolling 136 women from the state of Maranhão, 52 (38.2%) climacteric and 84 (61.8%) non-climacteric. Biometric, biochemical, hormonal and immunological parameters were analyzed. RESULTS: Climacteric women showed a moderately increased waist/hip ratio (0.894 versus 0.834, p < 0.05), sustained body mass index (27.46 versus 28.68, p > 0.05) increased leptin levels (9.59 versus 7.13, p < 0.05) and no evidence of metabolic syndrome. No other parameters were altered. The climacteric cohort didn't show significant body fat gains but displayed a typical age-related redistribution of adipose tissue. Even so, leptin levels were significantly elevated compared with non-climacteric women. CONCLUSIONS: Altogether, these data support the hypothesis that leptin is elevated, at least partially, as a function of age and climacterium and is not necessarily correlated with metabolic dysfunction and systemic inflammation. Further studies are needed to evaluate the impact of higher leptin levels on postmenopausal women. Arch Endocrinol Metab. 2020;64(3):276-81.


Assuntos
Adiposidade/fisiologia , Climatério/sangue , Leptina/sangue , Adulto , Fatores Etários , Idoso , Biomarcadores/sangue , Estudos de Casos e Controles , Climatério/fisiologia , Estudos de Coortes , Feminino , Humanos , Pessoa de Meia-Idade , Fatores Socioeconômicos
9.
Diabetes Res Clin Pract ; 165: 108226, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32446800

RESUMO

AIM: Studies on the effect of Ramadan diurnal intermittent fasting (RDIF) on glucometabolic markers have yielded conflicting results. We conducted ameta-analysis to estimate the effect size for changes in glucometabolic markers in healthy, non-athletic Muslims during Ramadan, and to assess the effect of variable covariates using meta-regression. METHODS: CINAHL, Cochrane, EBSCOhost, EMBASE, Google Scholar, ProQuest Medical, PubMed/MEDLINE, ScienceDirect, Scopus, and Web of Science databases were searched from date of inceptionto January 2020. The glucometabolic markers analyzed were: fasting glucose (FG), insulin, insulin resistance (HOMA-IR), leptin, and adiponectin. RESULTS: We identified seventy-two studies (3134 participants in total) that were conducted in 22 countries between 1982 and 2020. RDIF-induced effect sizes for the glucometabolic markers were: FG (no. of studies K = 61, number of subjects N = 2743, Hedges'g = -0.102, 95% CI: -0.194, -0.01); serum insulin (K = 16, N = 648, Hedges'g = 0.030 95% CI: -0.165, 0.226); HOMA-IR (K = 10, N = 349, Hedges'g = -0.012, 95% CI: -0.274, 0.250); leptin (K = 13, N = 442, Hedges'g = -0.010, 95% CI: -0.243, 0.223); and adiponectin (K = 11, N = 511, Hedges'g = 0.034, 95% CI: -0.227, 0.296). CONCLUSION: RDIF imposes no adverse metabolic impacts, and might help in improving some glucometabolic markers in healthy subjects.


Assuntos
Glicemia , Ritmo Circadiano , Jejum/sangue , Islamismo , Adiponectina/sangue , Adolescente , Adulto , Biomarcadores/sangue , Feminino , Voluntários Saudáveis , Férias e Feriados , Humanos , Insulina/sangue , Resistência à Insulina , Leptina/sangue , Masculino , Pessoa de Meia-Idade , Adulto Jovem
10.
Angiology ; 71(8): 754-761, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32431166

RESUMO

The study aimed to assess the role and the relationship of adipokines as well as parameters of arterial stiffness in newly diagnosed hypertension. Forty-nine newly diagnosed hypertensive cases (median age 47 ± 6 years) and 48 normotensive patients (median age 47 ± 6 years) were enrolled to this study. Patients underwent echocardiography, noninvasive assessment of hemodynamic parameters using SphygmoCor tonometer (Atcor Med). The levels of the adipokines-leptin, adiponectin, and resistin-were investigated. The augmentation pressure, augmentation index, and pulse wave velocity (PWV) were higher in patients with hypertension compared with controls (Ps < .05). Patients with hypertension had higher E/E' ratio, higher diameter of left atrium, and lower tricuspid annular plane systolic excursion compared with the control group (Ps < .05). Patients with hypertension had significant higher levels of leptin (ng/mL) and lower levels of adiponectin (µg/mL) compared with normotensive patients. The multivariate analysis showed that PWV (odds ratio [OR] 1.95, 95% CI, 1.2-2.9; P = .002) and leptin level (OR 1.01, 95% CI, 1.004-1.031; P = .01) were significantly associated with hypertension. Arterial stiffness as determined by PWV and leptin are associated with newly diagnosed hypertension. Elevated serum leptin level may influence the potential mechanism leading to sympathetic activation.


Assuntos
Pressão Arterial , Hipertensão/sangue , Leptina/sangue , Rigidez Vascular , Adiponectina/sangue , Adulto , Biomarcadores/sangue , Estudos de Casos e Controles , Feminino , Humanos , Hipertensão/diagnóstico , Hipertensão/fisiopatologia , Masculino , Pessoa de Meia-Idade , Análise de Onda de Pulso , Resistina/sangue , Regulação para Cima
11.
Ann Biol Clin (Paris) ; 78(3): 265-268, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32420886

RESUMO

Leptin and adiponectin are two adipokines. Their circulating concentrations, high for leptin and low for adiponectin, are predictive of insulin resistance and of an unfavorable cardiometabolic evolution in patients with obesity, metabolic syndrome or type 2 diabetes. In addition, recently, the adiponectin/leptin ratio has been proposed as an index of adipose tissue dysfunction together with threshold values for cardiometabolic risk for this index. The relevance and potential applications of the adiponectin/leptin and leptin/adiponectin ratios are discussed in the light of recent literature in this brief update.


Assuntos
Adiponectina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Técnicas de Diagnóstico Endócrino , Resistência à Insulina , Leptina/sangue , Adiponectina/análise , Biomarcadores/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Leptina/análise , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/metabolismo , Prognóstico , Fatores de Risco
12.
Ann Biol Clin (Paris) ; 78(3): 261-264, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32420889

RESUMO

Leptin and adiponectin are two adipokines currently used as biomarkers for diagnostic orientation and phenotyping in syndromes of lipodystrophy and severe insulin resistance. The level of these biomarkers also has an impact on the therapeutic management of the patients. These aspects, as well as our experience as a reference center, are described in this brief overview.


Assuntos
Adiponectina/fisiologia , Resistência à Insulina , Leptina/fisiologia , Lipodistrofia/diagnóstico , Síndrome Metabólica/diagnóstico , Adiponectina/sangue , Biomarcadores/análise , Biomarcadores/sangue , Humanos , Resistência à Insulina/fisiologia , Leptina/sangue , Lipodistrofia/patologia , Lipodistrofia/terapia , Síndrome Metabólica/terapia , Fenótipo , Índice de Gravidade de Doença
13.
Am J Physiol Regul Integr Comp Physiol ; 318(6): R1103-R1115, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32401626

RESUMO

This study aimed to investigate the effects of a short-term (36 h) fasting period combined with an acute bout of exercise on markers of immune function and inflammation in healthy human subjects. Fourteen moderately trained male subjects (aged 19-39 yr) participated in a 36-h fasting trial (FA-T), followed by an acute bout of moderate exercise (60% V̇o2max). After 1 wk, the same subjects, as their own control, participated in a nonfasting trial (NFA-T) in which they performed an exercise trial of the same duration and intensity. Blood samples were taken before, immediately after, and 1 h after each exercise bout and analyzed for several immunological and metabolic markers. At baseline, fasting subjects showed lower levels of T cell apoptosis, lymphocyte-proliferative responses, IL-6, monocyte chemoattractant protein-1 (MCP-1), insulin, and leptin (P < 0.05) as well as higher levels of neutrophil oxidative burst and thiobarbituric acid reactive substances (TBARS) than those in the NFA-T (P < 0.05). After the exercise protocol, fasted subjects revealed higher T cell apoptosis, neutrophil oxidative burst, TBARS, TNFα, and MCP-1 levels as well as lower levels of lymphocyte-proliferative response, IL-6, insulin, and leptin than those in the NFA-T (P < 0.05). Short-term fasting aggravates perturbations in markers of immune function, and inflammation was induced by an acute moderate-intensity exercise protocol.


Assuntos
Exercício Físico/fisiologia , Jejum/sangue , Inflamação/sangue , Adulto , Apoptose/fisiologia , Biomarcadores/sangue , Quimiocina CCL2/sangue , Voluntários Saudáveis , Humanos , Insulina/sangue , Interleucina-6/sangue , Leptina/sangue , Masculino , Estresse Oxidativo/fisiologia , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
14.
Arterioscler Thromb Vasc Biol ; 40(7): 1787-1800, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32460579

RESUMO

OBJECTIVE: Metabolic dysregulation and inflammation are important consequences of obesity and impact susceptibility to cardiovascular disease. Anti-inflammatory therapy in cardiovascular disease is being developed under the assumption that inflammatory pathways are identical in women and men, but it is not known if this is indeed the case. In this study, we assessed the sex-specific relation between inflammation and metabolic dysregulation in obesity. Approach and Results: Three hundred two individuals were included, half with a BMI 27 to 30 kg/m2 and half with a BMI>30 kg/m2, 45% were women. The presence of metabolic syndrome was assessed according to the National Cholesterol Education Program-ATPIII criteria, and inflammation was studied using circulating markers of inflammation, cell counts, and ex vivo cytokine production capacity of isolated immune cells. Additionally, lipidomic and metabolomic data were gathered, and subcutaneous fat biopsies were histologically assessed. Metabolic syndrome is associated with an increased inflammatory profile that profoundly differs between women and men: women with metabolic syndrome show a lower concentration of the anti-inflammatory adiponectin, whereas men show increased levels of several pro-inflammatory markers such as IL (interleukin)-6 and leptin. Adipose tissue inflammation showed similar sex-specific associations with these markers. Peripheral blood mononuclear cells isolated from men, but not women, with metabolic syndrome display enhanced cytokine production capacity. CONCLUSIONS: We identified sex-specific pathways that influence inflammation in obesity. Excessive production of proinflammatory cytokines was observed in men with metabolic syndrome. In contrast, women typically showed reduced levels of the anti-inflammatory adipokine adiponectin. These different mechanisms of inflammatory dysregulation between women and men with obesity argue for sex-specific therapeutic strategies.


Assuntos
Disparidades nos Níveis de Saúde , Mediadores da Inflamação/sangue , Inflamação/etiologia , Síndrome Metabólica/etiologia , Obesidade/complicações , Adiponectina/sangue , Idoso , Idoso de 80 Anos ou mais , Biomarcadores/sangue , Índice de Massa Corporal , Células Cultivadas , Feminino , Humanos , Inflamação/sangue , Inflamação/diagnóstico , Interleucina-6/sangue , Leptina/sangue , Leucócitos Mononucleares/metabolismo , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Metabolômica , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Fatores de Risco , Fatores Sexuais
15.
Artigo em Inglês | MEDLINE | ID: mdl-32292065

RESUMO

In rats, overnight fasting reduces the ability of systemic cholecystokinin-8 (CCK) to suppress food intake and to activate cFos in the caudal nucleus of the solitary tract (cNTS), specifically within glucagon-like peptide-1 (GLP-1) and noradrenergic (NA) neurons of the A2 cell group. Systemic CCK increases vagal sensory signaling to the cNTS, an effect that is amplified by leptin and reduced by ghrelin. Since fasting reduces plasma leptin and increases plasma ghrelin levels, we hypothesized that peripheral leptin administration and/or antagonism of ghrelin receptors in fasted rats would rescue the ability of CCK to activate GLP-1 neurons and a caudal subset of A2 neurons that coexpress prolactin-releasing peptide (PrRP). To test this, cFos expression was examined in ad libitum-fed and overnight food-deprived (DEP) rats after intraperitoneal CCK, after coadministration of leptin and CCK, or after intraperitoneal injection of a ghrelin receptor antagonist (GRA) before CCK. In fed rats, CCK activated cFos in ~60% of GLP-1 and PrRP neurons. Few or no GLP-1 or PrRP neurons expressed cFos in DEP rats treated with CCK alone, CCK combined with leptin, or GRA alone. However, GRA pretreatment increased the ability of CCK to activate GLP-1 and PrRP neurons and also enhanced the hypophagic effect of CCK in DEP rats. Considered together, these new findings suggest that reduced behavioral sensitivity to CCK in fasted rats is at least partially due to ghrelin-mediated suppression of hindbrain GLP-1 and PrRP neural responsiveness to CCK.


Assuntos
Regulação do Apetite/efeitos dos fármacos , Colecistocinina/administração & dosagem , Ingestão de Alimentos/efeitos dos fármacos , Jejum/metabolismo , Comportamento Alimentar/efeitos dos fármacos , Grelina/sangue , Neurônios/efeitos dos fármacos , Rombencéfalo/efeitos dos fármacos , Animais , Peptídeo 1 Semelhante ao Glucagon/metabolismo , Leptina/sangue , Masculino , Neurônios/metabolismo , Hormônio Liberador de Prolactina/metabolismo , Proteínas Proto-Oncogênicas c-fos/metabolismo , Ratos Sprague-Dawley , Receptores de Grelina/metabolismo , Rombencéfalo/metabolismo , Transdução de Sinais
16.
Nutr Metab Cardiovasc Dis ; 30(6): 922-924, 2020 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-32249141

RESUMO

Leptin is an adipose tissue-derived hormone primarily involved in the regulation of food intake. Leptine has been shown to have a much broader role than just regulating body weight and appetite in response to food intake: among the others, it has been associated with increased ROS production and inflammation, factors involved in the restoration of an effective myocardial reperfusion after myocardial revascularization. Our study, to our best knowledge, is the first showing a direct relationship between leptin serum levels, inflammatory mediators of the ischemia reperfusion damage and effective myocardial reperfusion in patients with ST elevation myocardial infarction undergoing primary percutaneous coronary intervention. Our findings suggest that leptin serum levels are directly associated with the inflammatory response during an acute myocardial infarction and may have a role in risk stratification in this clinical setting.


Assuntos
Mediadores da Inflamação/sangue , Leptina/sangue , Infarto do Miocárdio com Supradesnível do Segmento ST/sangue , Biomarcadores/sangue , Proteína C-Reativa/metabolismo , Humanos , Interleucina-6/sangue , Masculino , Intervenção Coronária Percutânea/efeitos adversos , Infarto do Miocárdio com Supradesnível do Segmento ST/diagnóstico , Infarto do Miocárdio com Supradesnível do Segmento ST/terapia , Fatores de Tempo , Resultado do Tratamento
17.
Ann Hum Biol ; 47(2): 159-165, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-32338077

RESUMO

Background: Leptin is potentially involved in the correction of early postnatal growth of infants having deviated from their genetic trajectory in utero.Aim: To analyse the potential mediating role of cord blood leptin level in the association between neonatal anthropometry and early postnatal growth in the mother-child EDEN cohort.Subjects and methods: We included term newborns with information on leptin, birth weight and length, and weight and length SD-score changes over the first 2 months. The Baron and Kenny method was used to quantify the mediation contribution of leptin in the association between neonatal anthropometry and postnatal growth, considering several confounders. Analyses were stratified to consider sexual dimorphism.Results: A 1 SD higher birth weight was associated with a lower 2-months weight variation of 0.27 (0.18; 0.36) SD and a 0.16 (0.06; 0.26) SD, in boys and girls, respectively. Leptin explained 20% and 25% of these associations, respectively. Leptin did not mediate the association between birth length and birth-to-2 months length variation.Conclusion: Our results suggest that cord blood leptin may not be involved in the negative association between birth length and postnatal length growth but may play a modest mediating role in early postnatal catch-up or catch-down in weight.


Assuntos
Tamanho Corporal , Desenvolvimento Infantil , Sangue Fetal/química , Recém-Nascido/fisiologia , Leptina/sangue , Pré-Escolar , Estudos de Coortes , Feminino , França , Humanos , Lactente , Recém-Nascido/crescimento & desenvolvimento , Masculino
18.
Arch Endocrinol Metab ; 64(1): 4-10, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32187268

RESUMO

Objective The aim of this study was to investigate polycystic ovary syndrome (PCOS) and to explore the relationship between body fat percentage and metabolic markers. Subjects and methods Sedentary women were assigned to PCOS (N = 60) and CONTROL (N = 60) groups. Each group was subdivided into three subgroups according to body fat percentage (22-27%, 27-32% and 32-37%). The protocol consisted of assessments of glucose, insulin, androgens, follicle stimulating hormone (FSH), luteinizing hormone (LH), 17-hydroxyprogesterone (17-OHP), leptin, adiponectin, tumor necrosis factor (TNF-α) and interleukin-6 (IL-6). Results The PCOS subgroups showed higher concentrations of androgens, LH and 17-OHP. Leptin showed direct relationship with increased body fat percentage, whereas adiponectin showed the inverse effect. However, both were unaffected by PCOS. TNF-α and IL-6 were higher in PCOS women and showed a direct relationship with increased body fat percentage. Glucose showed direct relationship with body fat percentage, whereas insulin presented higher values in PCOS women and direct relationship with increased body fat percentage. Conclusions Our findings indicate that PCOS and body fat percentage directly influence concentrations of insulin, TNF-α and IL-6, whereas leptin and adiponectin are influenced only by the increase in body fat percentage in these women. Arch Endocrinol Metab. 2020;64(1):4-10.


Assuntos
Tecido Adiposo/anatomia & histologia , Biomarcadores/sangue , Doenças Metabólicas/sangue , Síndrome do Ovário Policístico/sangue , 17-alfa-Hidroxiprogesterona/sangue , Adiponectina/sangue , Adolescente , Adulto , Androgênios/sangue , Índice de Massa Corporal , Estudos de Casos e Controles , Feminino , Hormônio Foliculoestimulante/sangue , Glucose/análise , Humanos , Insulina/sangue , Resistência à Insulina , Interleucina-6/sangue , Leptina/sangue , Hormônio Luteinizante/sangue , Fatores de Risco , Comportamento Sedentário , Fator de Necrose Tumoral alfa/sangue , Adulto Jovem
19.
Medicine (Baltimore) ; 99(6): e19052, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-32028423

RESUMO

Disturbances in adipocytokine profiles can contribute to peripheral insulin resistance and impairment of insulin production, which are 2 primary pathophysiological mechanisms involved in type 2 diabetes mellitus (T2DM). Previous studies of disturbed adipocytokine profiles have resulted in ambiguous findings; therefore, we conducted the current study comparing leptin, resistin, and adiponectin concentrations in patients with newly diagnosed T2DM who had normal body mass index (BMI) and those who were obese.We studied a population-based cohort of healthy participants and those with newly diagnosed T2DM. A normal BMI group was randomly selected; age- and sex-matched obese participants were recruited. Circulating leptin, resistin, and adiponectin concentrations were measured and compared between groups using analysis of variance; binary logistic regression analysis was then performed to compare the normal BMI and obese groups.In total, 85 healthy participants and 38 patients with diabetes (19 with normal BMI and 17 who were obese) were enrolled. After adjustment for BMI and waist circumference, the median leptin concentration was higher in the obese group (6.77 (3.89-10.73) ng/mL) than in the normal BMI group (1.69 (0.80-3.89) ng/mL) (P = .007), whereas the median adiponectin concentration was lower in the obese group (1.03 (0.75-2.36) µg/mL vs 3.36 (0.59-7.63) µg/mL, P = .03). In addition, the adiponectin/leptin ratio was higher in the normal BMI group (145.6 (41.3-495.9) ng/mL) than in the obese group (20.55 (8.74-36.94) ng/mL, P = .002).Compared with the normal BMI T2DM group, the obese T2DM group exhibited a disturbed adipocytokine profile in the form of a significantly increased leptin concentration and reduced adiponectin level. Further studies are needed to determine the causal relationship for this difference and evaluate its importance for personalized diabetic treatment.


Assuntos
Adiponectina/sangue , Diabetes Mellitus Tipo 2/sangue , Leptina/sangue , Obesidade/sangue , Resistina/sangue , Adulto , Índice de Massa Corporal , Estudos de Casos e Controles , Estudos Transversais , Diabetes Mellitus Tipo 2/complicações , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Obesidade/complicações , Circunferência da Cintura
20.
Life Sci ; 247: 117442, 2020 Apr 15.
Artigo em Inglês | MEDLINE | ID: mdl-32081663

RESUMO

Transient receptor potential vanilloid type 1 (TRPV1) channels are emerging therapeutic targets for metabolic disorders. Berberine, which is a modulator of TRPV1, has proven antiobesity and antidiabetic potentials. The present study was aimed to investigate the protective effects of berberine in olanzapine-induced alterations in hypothalamic appetite control, inflammation and metabolic aberrations in mice targeting TRPV1 channels. Female BALB/c mice (18-23 g) were treated with olanzapine (6 mg/kg, p.o.) for six weeks to induce metabolic alterations, while berberine (100 and 200 mg/kg, p.o.) and metformin (100 mg/kg, p.o) were used as test and standard interventions respectively. Weekly assessment of feed-water intake, body temperature and body weight was done, while locomotion was measured at the end of week 1 and 6. Serum glucose and lipid profile were assessed by biochemical methods, while other serum biomarkers were assessed by ELISA. qPCR was used to quantify the mRNA expression in the hypothalamus. Olanzapine treatment significantly increased the feed intake, weight gain, adiposity index, while reduced body temperature and locomotor activity which were reversed by berberine treatment. Berberine treatment reduced serum ghrelin and leptin levels as well decrease in hypothalamic mRNA expression of orexigenic neuropeptides, inflammatory markers and ghrelin receptor in olanzapine-treated mice. Olanzapine treatment increased expression of TRPV1/TRPV3 in the hypothalamus which was significantly decreased by berberine treatment. Our results suggest that berberine, by TRPV1/TRPV3 modulation, attenuated the olanzapine-induced metabolic alterations in mice. Hence berberine supplementation in psychiatric patients could be a preventive approach to reduce the metabolic adverse effects of antipsychotics.


Assuntos
Antipsicóticos/uso terapêutico , Berberina/uso terapêutico , Doenças Metabólicas/tratamento farmacológico , Olanzapina/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Antipsicóticos/efeitos adversos , Berberina/efeitos adversos , Temperatura Corporal , Peso Corporal , Citocinas/metabolismo , Ingestão de Líquidos , Feminino , Regulação da Expressão Gênica/efeitos dos fármacos , Grelina/sangue , Grelina/metabolismo , Hipotálamo/metabolismo , Leptina/sangue , Leptina/metabolismo , Metformina/farmacologia , Metformina/uso terapêutico , Camundongos , Camundongos Endogâmicos BALB C , Terapia de Alvo Molecular/métodos , Neuropeptídeos/metabolismo , Obesidade , RNA Mensageiro , Transdução de Sinais , Canais de Cátion TRPV/genética , Resultado do Tratamento
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