Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 11.292
Filtrar
1.
Nat Commun ; 12(1): 1041, 2021 02 15.
Artículo en Inglés | MEDLINE | ID: mdl-33589633

RESUMEN

Growing evidence supports that pharmacological application of growth differentiation factor 15 (GDF15) suppresses appetite but also promotes sickness-like behaviors in rodents via GDNF family receptor α-like (GFRAL)-dependent mechanisms. Conversely, the endogenous regulation of GDF15 and its physiological effects on energy homeostasis and behavior remain elusive. Here we show, in four independent human studies that prolonged endurance exercise increases circulating GDF15 to levels otherwise only observed in pathophysiological conditions. This exercise-induced increase can be recapitulated in mice and is accompanied by increased Gdf15 expression in the liver, skeletal muscle, and heart muscle. However, whereas pharmacological GDF15 inhibits appetite and suppresses voluntary running activity via GFRAL, the physiological induction of GDF15 by exercise does not. In summary, exercise-induced circulating GDF15 correlates with the duration of endurance exercise. Yet, higher GDF15 levels after exercise are not sufficient to evoke canonical pharmacological GDF15 effects on appetite or responsible for diminishing exercise motivation.


Asunto(s)
Regulación del Apetito/fisiología , Ejercicio Físico/fisiología , Conducta Alimentaria/fisiología , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Factor 15 de Diferenciación de Crecimiento/genética , Resistencia Física/fisiología , Adulto , Animales , Creatina Quinasa/sangre , Creatina Quinasa/genética , Regulación de la Expresión Génica , Receptores del Factor Neurotrófico Derivado de la Línea Celular Glial/deficiencia , Factor 15 de Diferenciación de Crecimiento/sangre , Factor 15 de Diferenciación de Crecimiento/metabolismo , Humanos , Interleucina-10/sangre , Interleucina-10/genética , Interleucina-6/administración & dosificación , Leptina/sangre , Leptina/genética , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Ratones , Ratones Noqueados , Motivación/fisiología , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Miocardio/metabolismo , Condicionamiento Físico Animal , Factores de Tiempo
2.
Metabolism ; 114: 154429, 2021 01.
Artículo en Inglés | MEDLINE | ID: mdl-33166579

RESUMEN

OBJECTIVE: The systemic function of CETP has been well characterized. CETP plasma activity reduces HDL cholesterol and thus increases the risk of atherosclerosis. Here, we investigated whether CETP expression modulate adiposity. METHODS: Body adiposity and energy metabolism related assays and gene/protein expression were compared in CETP transgenic and non-transgenic mice and in hamsters treated with CETP neutralizing antibody. RESULTS: We found that transgenic mice expressing human CETP present less white adipose tissue mass and lower leptinemia than nontransgenic (NTg) littermates. No differences were found in physical activity, food intake, fat fecal excretion, lipogenesis or exogenous lipid accumulation in adipose depots. Nonetheless, adipose lipolysis rates and whole-body energy expenditure were elevated in CETP mice. In accordance, lipolysis-related gene expression and protein content were increased in visceral and brown adipose tissue (BAT). In addition, we verified increased BAT temperature and oxygen consumption. These results were confirmed in two other animal models: 1) hamsters treated with CETP neutralizing antibody and 2) an independent line of transgenic mice expressing simian CETP. CONCLUSIONS: These findings reveal a novel anti-adipogenic role for CETP.


Asunto(s)
Tejido Adiposo Pardo/metabolismo , Adiposidad/fisiología , Proteínas de Transferencia de Ésteres de Colesterol/metabolismo , Lipólisis/fisiología , Hígado/metabolismo , Animales , Anticuerpos Neutralizantes , Proteínas de Transferencia de Ésteres de Colesterol/genética , Cricetinae , Ingestión de Alimentos/fisiología , Metabolismo Energético/fisiología , Leptina/sangre , Ratones , Ratones Transgénicos , Actividad Motora/fisiología
3.
Chemosphere ; 262: 127841, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-32784060

RESUMEN

Environmental pollutants suspected of disrupting the endocrine system are considered etiologic factors in the epidemic of metabolic disorders. As regulation of energy metabolism relies on the integrated action of a large number of hormones, we hypothesized that certain chemicals could trigger changes in glucocorticoid signaling. To this end, we exposed C57Bl6/J female and male mice between 5 and 20 weeks of age to a mixture of 2,3,7,8- tetrachlorodibenzo-p-dioxin (20 pg/kg body weight/day [bw/d]), polychlorobiphenyl 153 (200 ng/kg bw/d), di-[2-ethylhexyl]-phthalate (500 µg/kg bw/d) and bisphenol A (40 µg/kg bw/d). In female mice fed a standard diet (ST), we observed a decrease in plasma levels of leptin as well as a reduced expression of corticoid receptors Nr3c1 and Nr3c2, of leptin and of various canonical genes related to the circadian clock machinery in visceral (VAT) but not subcutaneous (SAT) adipose tissue. However, Nr3c1 and Nr3c2 mRNA levels did not change in high-fat-fed females exposed to pollutants. In ST-fed males, pollutants caused the same decrease of Nr3c1 mRNA levels in VAT observed in ST-fed females but levels of Nr3c2 and other clock-related genes found to be down-regulated in female VAT were enhanced in male SAT and not affected in male VAT. The expression of corticoid receptors was not affected in the livers of both sexes in response to pollutants. In summary, exposure to a mixture of pollutants at doses lower than the no-observed adverse effect levels (NoAELs) resulted in sex-dependent glucocorticoid signaling disturbances and clock-related gene expression modifications in the adipose tissue of ST-fed mice.


Asunto(s)
Contaminantes Ambientales/toxicidad , Glucocorticoides/metabolismo , Tejido Adiposo/metabolismo , Animales , Compuestos de Bencidrilo , Peso Corporal , Contaminantes Ambientales/metabolismo , Femenino , Expresión Génica , Leptina/sangre , Hígado/metabolismo , Masculino , Ratones , Ratones Endogámicos C57BL , Fenoles , Dibenzodioxinas Policloradas/metabolismo , ARN Mensajero/metabolismo , Sensibilidad y Especificidad
4.
Medicine (Baltimore) ; 99(51): e23773, 2020 Dec 18.
Artículo en Inglés | MEDLINE | ID: mdl-33371145

RESUMEN

ABSTRACT: Chagas disease affects approximately 7 million people, causing disability and mortality in the most productive life stages of infected individuals. Considering the lifestyle of the world population, metabolic syndrome is a synergistic factor for an increased cardiovascular risk of patients with Chagas disease.This study transversally evaluated the metabolic and immunological profiles of patients with indeterminate (IF) and cardiac (CF) forms of Chagas disease and their correlations with left ventricular dysfunction (LVD).Clinical and electrical bioimpedance analysis, levels of cytokines (interferon [IFN]-γ, tumor necrosis factor [TNF]-α, interleukin [IL]-17, IL-10, and IL-33) and adipocytokines (adiponectin, leptin, and resistin), metabolic syndrome components, and brain natriuretic peptide (BNP) levels were assessed in 57 patients (13 IF and 44 CF) with a mean age of 61.63 ±â€Š12.1 years. Chest x-ray, electrocardiogram, and echocardiogram were performed to classify the clinical forms.The CF group had a higher number of individuals with metabolic syndrome components blood pressure altered, while more participants in the CF group with LVD had low high-density lipoprotein (HDL) levels. The IF group had more participants with a higher waist-to-hip ratio (WHR). No significant difference was observed between metabolic syndrome, cytokine and adipocytokine level, and clinical forms of the disease or in relation to LVD.Individuals with the IF showed metabolic and immunological profiles compatible with increased disease control, whereas those with CF showed marked inflammatory immune response.


Asunto(s)
Enfermedad de Chagas/inmunología , Enfermedad de Chagas/metabolismo , Adiponectina/análisis , Adiponectina/sangre , Anciano , Análisis de Varianza , Biomarcadores/análisis , Biomarcadores/sangre , Femenino , Cardiopatías/inmunología , Cardiopatías/metabolismo , Humanos , Interleucina-10/análisis , Interleucina-10/sangre , Interleucina-17/análisis , Interleucina-17/biosíntesis , Interleucina-33/análisis , Interleucina-33/sangre , Leptina/análisis , Leptina/sangre , Masculino , Persona de Mediana Edad , Resistina/análisis , Resistina/sangre , Estadísticas no Paramétricas
5.
Vasc Health Risk Manag ; 16: 535-543, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-33324067

RESUMEN

Introduction: The aim of this study was to evaluate the relationship between adipokines and arterial stiffness in a group of 85 elderly subjects and the role of leptin and adiponectin on subclinical vascular damage, defined by a PWV>10 m/s. Methods: In each subject, we evaluated anthropometry, body composition by DXA (fat mass, fat mass%, lean mass), metabolic variables, leptin, adiponectin, systolic, diastolic, mean arterial pressure and pulse pressure (SBP, DBP, MAP, PP), carotid-femoral pulse wave velocity (cfPWV) and carotid-radial pulse wave velocity (crPWV). Results: In the study population, significant associations were observed between cfPWV and crPWV, age, SBP, MAP, waist circumference, fat body mass and leptin. The study population was subdivided in 2 subgroups according to adipokine patterns: group 1 included patients with high adiponectin and low leptin, and group 2 patients had high leptin and low adiponectin. SBP, PP, cfPWV were significantly higher in subjects with high leptin and low adiponectin (group 2). Even after adjustment for gender, fat mass%, MAP, HDL cholesterol and triglycerides, cfPWV was higher in group 2 than group 1. In a logistic binary regression on the entire population, considering subclinical vascular damage as a dependent variable and age, gender, MAP, fat mass%, triglycerides, HDL cholesterol and category of subjects with high leptin and low adiponectin as independent variables, MAP and category of subjects with high leptin and low adiponectin were significant predictors (OR, respectively, 1.09 and 3.61). Conclusion: In conclusion, in the elderly, the presence at the same time of high leptin levels and low adiponectin levels seems to have synergic effects on arterial stiffness.


Asunto(s)
Adiponectina/sangre , Envejecimiento/sangre , Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , Leptina/sangre , Rigidez Vascular , Factores de Edad , Anciano , Anciano de 80 o más Años , Biomarcadores/sangre , Composición Corporal , Enfermedades Cardiovasculares/diagnóstico , Femenino , Humanos , Masculino , Factores de Riesgo
6.
Am J Physiol Renal Physiol ; 319(3): F469-F475, 2020 09 01.
Artículo en Inglés | MEDLINE | ID: mdl-32744085

RESUMEN

A lower 24-h urine pH (24h-pH), i.e., a higher renal excretion of free protons, at a given acid load to the body, denotes a reduction in the kidney's capacity for net acid excretion (NAE). There is increasing evidence, not only for patients with type 2 diabetes but also for healthy individuals, that higher body fatness or waist circumference (WC) has a negative impact on renal function to excrete acids (NAE). We hypothesized that adiposity-related inflammation molecules might mediate this relation between adiposity and renal acid excretion function. Twelve biomarkers of inflammation were measured in fasting blood samples from 162 adult participants (18-25 yr old) of the Dortmund Nutritional and Anthropometric Longitudinally Designed (DONALD) study who had undergone anthropometric measurements and collected 24-h urine samples. Both Baron and Kenny's (B&K's) steps to test mediation and causal mediation analysis were conducted to examine the potential mediatory roles of biomarkers of inflammation in the WC-24-h pH relationship after strictly controlling for laboratory-measured NAE. In B&K's mediation analysis, leptin, soluble intercellular adhesion molecule 1 (sICAM-1), and adiponectin significantly associated with the outcome 24-h pH and attenuated the WC-pH relation. In agreement herewith, causal mediation analysis estimated the "natural indirect effects" of WC on 24-h pH via leptin (P = 0.01) and adiponectin (P = 0.03) to be significant, with a trend for sICAM-1 (P = 0.09). The calculated proportions mediated by leptin, adiponectin, and sICAM-1 were 64%, 23%, and 12%, respectively. Both mediation analyses identified an inflammatory cytokine (leptin) and an anti-inflammatory cytokine (adiponectin) along with sICAM-1 as being potentially involved in mediating adiposity-related influences on renal acid excretion capacity.


Asunto(s)
Adiponectina/metabolismo , Tejido Adiposo/metabolismo , Inflamación/metabolismo , Molécula 1 de Adhesión Intercelular/metabolismo , Riñón/metabolismo , Leptina/metabolismo , Adiponectina/sangre , Adiponectina/genética , Adolescente , Adulto , Biomarcadores/sangre , Femenino , Humanos , Molécula 1 de Adhesión Intercelular/sangre , Molécula 1 de Adhesión Intercelular/genética , Leptina/sangre , Leptina/genética , Masculino , Urinálisis , Adulto Joven
7.
PLoS One ; 15(8): e0237922, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32845924

RESUMEN

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.


Asunto(s)
Ritmo Circadiano/fisiología , Ayuno/sangre , Ghrelina/sangre , Hidrocortisona/sangre , Melatonina/sangre , Obesidad/sangre , Obesidad/fisiopatología , Adulto , Dieta , Ingestión de Energía , Femenino , Hemodinámica , Humanos , Leptina/sangre , Lípidos/sangre , Masculino , Estudios Prospectivos , Sueño/fisiología
8.
High Blood Press Cardiovasc Prev ; 27(6): 505-513, 2020 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-32780307

RESUMEN

INTRODUCTION: Leptin is associated with cardiovascular risk. Some studies analyzed the potential association between leptin and arterial stiffness, an independent cardiovascular risk factor. However, the studies that investigated this association provided inconsistent and heterogeneous results. AIM: We performed a systematic review and a meta-analysis of the available studies on the relationship between leptin and arterial stiffness to achieve definitive conclusions. METHODS: A systematic search of the on-line databases available (up to December 2019) was conducted including the observational studies that reported the evaluation of the relationship between non-invasively assessed arterial stiffness (expressed by carotid-femoral pulse wave velocity) and leptin. For each study, the effect size was standardized and pooled using a random effect model. Sensitivity analysis, heterogeneity, publication bias, meta-regression and sub-group analyses were also assessed. RESULTS: Ten studies met the pre-defined inclusion criteria and provided 11 cohorts with 7,580 total participants. Leptin levels were positively and significantly associated with risk of increased arterial stiffness (odds ratio 1.04; p < 0.01), with no significant heterogeneity among studies. Likewise, pooled analysis of correlation showed a significant and positive association between leptin and pulse wave velocity (z = 0.27, p < 0.01), with significant heterogeneity among studies. CONCLUSION: The results of this meta-analysis indicate that leptin is positively associated with arterial stiffness. This association significantly adds to the recognized value of leptin in cardiovascular disease.


Asunto(s)
Enfermedades Cardiovasculares/sangre , Enfermedades Cardiovasculares/fisiopatología , Leptina/sangre , Rigidez Vascular , Anciano , Biomarcadores/sangre , Enfermedades Cardiovasculares/epidemiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Observacionales como Asunto , Pronóstico , Medición de Riesgo , Factores de Riesgo
9.
PLoS One ; 15(8): e0237708, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32817646

RESUMEN

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.


Asunto(s)
Hipertensión/sangre , Leptina/sangre , Obesidad/sangre , Factor de Crecimiento Placentario/sangre , Efectos Tardíos de la Exposición Prenatal/sangre , Adiposidad/genética , Animales , Presión Sanguínea/genética , Peso Corporal/genética , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Femenino , Humanos , Hipertensión/genética , Hipertensión/fisiopatología , Masculino , Herencia Materna/genética , Obesidad/genética , Obesidad/fisiopatología , Embarazo , Efectos Tardíos de la Exposición Prenatal/fisiopatología , Ratas , Destete
10.
Artículo en Inglés | MEDLINE | ID: mdl-32854366

RESUMEN

Obesity is related to low-grade systemic inflammation. This state of inflammation is characterized by the alteration in adipokine regulation, which may lead to a situation of cardiometabolic risk. The aim of this study was to evaluate the effects of a concurrent training program on markers of lipoinflammation in adult people with obesity, comparing the response to the training between men and women. A quasi-experimental, quantitative, and longitudinal study with a pre-post intervention was conducted. An 8-week concurrent training program was carried out, in which 26 individuals with obesity participated (mean ± SD; age = 46.38 ± 4.66) (BMI = 36.05 ± 4.99) (12 men and 14 women). Before and after the intervention period, blood samples were taken by percutaneous puncture. The blood levels of adiponectin and leptin were evaluated. Significant differences were obtained in the adiponectin-leptin ratio (A/L ratio) of the entire sample (p = 0.009, ES = 0.53), which indicates a decrease in the risk of cardiovascular diseases and lipoinflammation. There were no significant differences in the improvements observed after the training in A/L ratio between women (A/L change = +63.5%) and men (A/L change= +59.2%). It can be concluded that the combination of aerobic exercise and resistance training induced an improvement in markers of lipoinflammation and cardiometabolic risk in the individuals with obesity evaluated in this study.


Asunto(s)
Adiponectina/sangre , Leptina/sangre , Obesidad/terapia , Adulto , Biomarcadores/sangre , Índice de Masa Corporal , Ejercicio Físico , Terapia por Ejercicio , Femenino , Humanos , Estudios Longitudinales , Masculino , Persona de Mediana Edad , Obesidad/sangre , Reproducibilidad de los Resultados , Conducta Sedentaria , Factores Sexuales
11.
Int J Obes (Lond) ; 44(9): 1810-1817, 2020 09.
Artículo en Inglés | MEDLINE | ID: mdl-32647360

RESUMEN

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.


Asunto(s)
Infecciones por Coronavirus , Leptina , Obesidad , Pandemias , Neumonía Viral , Betacoronavirus , Comorbilidad , Infecciones por Coronavirus/epidemiología , Infecciones por Coronavirus/inmunología , Infecciones por Coronavirus/metabolismo , Interacciones Huésped-Patógeno/inmunología , Humanos , Leptina/sangre , Leptina/inmunología , Leptina/metabolismo , Obesidad/epidemiología , Obesidad/inmunología , Obesidad/metabolismo , Neumonía Viral/epidemiología , Neumonía Viral/inmunología , Neumonía Viral/metabolismo , Transducción de Señal/inmunología
12.
Toxicol Lett ; 332: 42-55, 2020 Oct 10.
Artículo en Inglés | MEDLINE | ID: mdl-32629074

RESUMEN

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.


Asunto(s)
Carbohidratos de la Dieta/toxicidad , Reserva Ovárica/efectos de los fármacos , Ovario/metabolismo , Síndrome del Ovario Poliquístico/inducido químicamente , Adiposidad/efectos de los fármacos , Animales , Peso Corporal , Dieta , Ciclo Estral/efectos de los fármacos , Femenino , Fibrosis , Intolerancia a la Glucosa/sangre , Intolerancia a la Glucosa/inducido químicamente , Resistencia a la Insulina , Leptina/sangre , Metabolismo de los Lípidos , Folículo Ovárico/efectos de los fármacos , Ovario/patología , Estrés Oxidativo , Síndrome del Ovario Poliquístico/metabolismo , Síndrome del Ovario Poliquístico/patología , Ratas , Ratas Wistar
13.
Am J Physiol Endocrinol Metab ; 319(2): E354-E362, 2020 08 01.
Artículo en Inglés | MEDLINE | ID: mdl-32603260

RESUMEN

Browning of white adipose tissue (WAT) has been shown to reduce obesity and obesity-related complications, suggesting that factors that promote WAT browning may have applications in the development of therapeutic strategies for treating obesity. Here, we show that ablation of spinophilin (SPL), a ubiquitously expressed, multidomain scaffolding protein, increases metabolism and improves energy balance. Male and female SPL knockout (KO) and wild-type (WT) littermate controls were fed a chow diet or a high-fat diet (HFD). Body weight, hepatic steatosis, glucose and insulin tolerance, physical activity, and expression of browning genes in adipose tissues were measured and compared. Male SPL knockout (KO) mice fed a chow diet were significantly leaner, had lower body weights, and exhibited better glucose tolerance and insulin sensitivity than wild-type (WT) littermate controls. When fed an HFD, SPL KO mice were protected from increased body fat, weight gain, hepatic steatosis, hyperinsulinemia, and insulin resistance. Physical activity of SPL KO mice was markedly increased compared with WT controls. Furthermore, expression of the brown adipocyte marker, uncoupling protein-1 (UCP-1), and the mitochondrial activity markers, cd137 and c-idea, were significantly increased in visceral WAT (vWAT) of SPL KO mice, suggesting that SPL knockout protected the mice from HFD-induced obesity and its metabolic complications, at least in part, by promoting the browning of white adipocytes in vWAT. Our data identify a critical role of SPL in regulating glucose homeostasis, obesity, and adipocyte browning. These results suggest SPL may serve as a drug target for obesity and diabetes.


Asunto(s)
Dieta Alta en Grasa/efectos adversos , Resistencia a la Insulina/fisiología , Proteínas de Microfilamentos/deficiencia , Proteínas del Tejido Nervioso/deficiencia , Obesidad/prevención & control , Adiponectina/sangre , Tejido Adiposo Pardo/fisiopatología , Tejido Adiposo Blanco/fisiopatología , Animales , Metabolismo Energético , Hígado Graso/fisiopatología , Hígado Graso/prevención & control , Femenino , Leptina/sangre , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Proteínas de Microfilamentos/fisiología , Proteínas del Tejido Nervioso/fisiología , Obesidad/etiología , Obesidad/fisiopatología , Esfuerzo Físico/fisiología
14.
Nature ; 583(7817): 620-624, 2020 07.
Artículo en Inglés | MEDLINE | ID: mdl-32669709

RESUMEN

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.


Asunto(s)
Neoplasias de la Mama/dietoterapia , Neoplasias de la Mama/tratamiento farmacológico , Dietoterapia/métodos , Ayuno/fisiología , Fulvestrant/uso terapéutico , Animales , Factores Biológicos/sangre , Neoplasias de la Mama/patología , Dieta Saludable/métodos , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Resistencia a Antineoplásicos/efectos de los fármacos , Proteína 1 de la Respuesta de Crecimiento Precoz/metabolismo , Femenino , Fulvestrant/administración & dosificación , Humanos , Insulina/sangre , Factor I del Crecimiento Similar a la Insulina/metabolismo , Leptina/sangre , Células MCF-7 , Ratones Endogámicos NOD , Ratones SCID , Fosfohidrolasa PTEN/metabolismo , Piperazinas/administración & dosificación , Piperazinas/uso terapéutico , Piridinas/administración & dosificación , Piridinas/uso terapéutico , Receptores Estrogénicos , Receptores de Progesterona , Tamoxifeno/efectos adversos , Tamoxifeno/uso terapéutico , Ensayos Antitumor por Modelo de Xenoinjerto
15.
Anim Sci J ; 91(1): e13426, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32672407

RESUMEN

Circulating leptin concentrations could potentially be used as a predictor of production traits in cattle. This study aimed to clarify the correlations between circulating leptin concentrations and growth performance, carcass traits, and meat quality indexes in finishing bulls fed high-concentrate diets (concentrate-to-forage ratio 70:30). Fifty-seven Simmental × Luxi F1 crossbred bulls were used for 112-day finishing experiment. Circulating leptin concentrations and relevant indexes of growth performance, and carcass traits and meat quality were measured during or after finishing trail. The results indicated that the leptin concentrations tended to be negatively correlated with dry matter intake (DMI) (r = -.233, p = .081), and were positively correlated with 12th-rib fat thickness (r = .330, p = .012), marbling score (r = .336, p = .011), and intramuscular fat content (r = .368, p = .021). Moreover, the leptin concentrations were negatively correlated with cholesterol content (r = -.339, p = .037) and were not correlated with sensory indexes including tenderness, juiciness, and like flavor (p > .05). In conclusion, circulating leptin concentrations may potentially be used as a predictor of carcass traits related to content of fat and beef quality traits related to content of cholesterol in finishing bulls fed high-concentrate diets.


Asunto(s)
Fenómenos Fisiológicos Nutricionales de los Animales , Bovinos/sangre , Bovinos/crecimiento & desarrollo , Dieta/veterinaria , Calidad de los Alimentos , Leptina/sangre , Carácter Cuantitativo Heredable , Carne Roja , Animales , Distribución de la Grasa Corporal , Bovinos/genética , Bovinos/metabolismo , Colesterol/sangre , Ingestión de Alimentos , Masculino
16.
High Blood Press Cardiovasc Prev ; 27(5): 379-388, 2020 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-32705504

RESUMEN

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.


Asunto(s)
Adipoquinas/sangre , Amlodipino/uso terapéutico , Bloqueadores del Receptor Tipo 1 de Angiotensina II/uso terapéutico , Antihipertensivos/uso terapéutico , Bloqueadores de los Canales de Calcio/uso terapéutico , Ecocardiografía , Hipertensión/terapia , Valsartán/uso terapéutico , Función Ventricular Izquierda/efectos de los fármacos , Remodelación Ventricular/efectos de los fármacos , Adiponectina/sangre , Adulto , Amlodipino/efectos adversos , Bloqueadores del Receptor Tipo 1 de Angiotensina II/efectos adversos , Antihipertensivos/efectos adversos , Biomarcadores/sangre , Proteína C-Reactiva/metabolismo , Bloqueadores de los Canales de Calcio/efectos adversos , Egipto , Femenino , Humanos , Hipertensión/sangre , Hipertensión/diagnóstico por imagen , Hipertensión/fisiopatología , Leptina/sangre , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Factores de Tiempo , Resultado del Tratamiento , Factor de Necrosis Tumoral alfa/sangre , Valsartán/efectos adversos
17.
Nutr Metab Cardiovasc Dis ; 30(8): 1306-1314, 2020 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-32507340

RESUMEN

BACKGROUND AND AIMS: In the present study, we assessed the extent of mediation by low-grade systemic inflammation and adipokines in the association between abdominal adiposity and insulin resistance. METHODS AND RESULTS: In this cross-sectional analysis of baseline measurements of the Netherlands Epidemiology of Obesity study, total body fat (TBF) was measured in all (n = 5772) participants who did not have missing data and neither used glucose-lowering medication, and abdominal subcutaneous adipose tissue (aSAT) and visceral adipose tissue (VAT) were assessed by MRI in a random subgroup (n = 2448). C-reactive protein (CRP), adiponectin, and leptin were considered as potential mediators, and insulin resistance was assessed by Homeostatic Model Assessment of Insulin Resistance (HOMA-IR). Mediation by CRP, adiponectin, and leptin was studied by including the mediators to the fully adjusted linear regression model. Participants had a mean (SD) age of 56 (6) years, TBF of 36 (9) %, VAT of 119 (61) cm2 and aSAT of 300 (111) cm2. Per SD of TBF, VAT and aSAT, HOMA-IR was 64% (95% confidence interval [CI]: 59-70), 33% (95%CI: 28-42) and 20% (95%CI: 14-26) higher, respectively. The association between aSAT and HOMA-IR fully disappeared after adjustment for leptin; the association between VAT and HOMA-IR attenuated after adjustment for leptin (22%) and adiponectin (15%). No mediation was observed by CRP, and mediation estimates were similar in men and women. CONCLUSION: Where leptin fully explained the aSAT-HOMA-IR association, the VAT-HOMA-IR association was only partly explained by leptin and adiponectin similarly in men and women.


Asunto(s)
Adiponectina/sangre , Proteína C-Reactiva/metabolismo , Resistencia a la Insulina , Grasa Intraabdominal/metabolismo , Leptina/sangre , Obesidad Abdominal/sangre , Grasa Subcutánea/metabolismo , Adiposidad , Factores de Edad , Biomarcadores/sangre , Estudios Transversales , Femenino , Humanos , Grasa Intraabdominal/diagnóstico por imagen , Grasa Intraabdominal/fisiopatología , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Países Bajos/epidemiología , Obesidad Abdominal/diagnóstico , Obesidad Abdominal/epidemiología , Obesidad Abdominal/fisiopatología , Estudios Prospectivos , Factores de Riesgo , Grasa Subcutánea/diagnóstico por imagen , Grasa Subcutánea/fisiopatología
18.
Nutr Metab Cardiovasc Dis ; 30(8): 1375-1381, 2020 07 24.
Artículo en Inglés | MEDLINE | ID: mdl-32571614

RESUMEN

BACKGROUND AND AIMS: Obesity is a pro-inflammatory risk factor for progression of CKD and cardiovascular disease. We hypothesized that implementation of caloric restriction and endurance exercise would improve adipocytokine profiles in patients with moderate to severe CKD. METHODS AND RESULTS: We enrolled patients with moderate to severe CKD through a multi-center pilot randomized trial of diet and exercise in a 4-arm design (dietary restriction of 10%-15% reduction in caloric intake, exercise three times/week, combined diet and exercise, and control) (NCT01150851). Adipocytokines (adiponectin and leptin) were measured at the beginning and end of the study period as secondary outcomes. Treatment effect was analyzed in a multivariable model adjusted for baseline outcome values, age, gender, site and diabetes. A total of 122 participants were consented, 111 were randomized (42% female, 25% diabetic, and 91% hypertensive), 104 started intervention and 92 completed the study (Figure 1). Plasma adiponectin levels increased significantly in response to diet by 23% (95% CI: 0.2%, 49.8%, p = 0.048) among participants randomized to the caloric restriction and usual activity arm but not to exercise, whereas circulating leptin did not change by either treatment. CONCLUSION: Our data suggest that dietary caloric restriction increases plasma adiponectin levels in stage 3-4 CKD patients, with limited effect on leptin levels. These findings suggest the potential for improving the metabolic milieu of CKD with moderate calorie restriction.


Asunto(s)
Adipoquinas/sangre , Restricción Calórica , Terapia por Ejercicio , Insuficiencia Renal Crónica/terapia , Adiponectina/sangre , Adulto , Anciano , Biomarcadores/sangre , Femenino , Humanos , Leptina/sangre , Masculino , Persona de Mediana Edad , Resistencia Física , Proyectos Piloto , Insuficiencia Renal Crónica/sangre , Insuficiencia Renal Crónica/diagnóstico , Índice de Severidad de la Enfermedad , Factores de Tiempo , Resultado del Tratamiento , Estados Unidos
19.
PLoS One ; 15(6): e0234465, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32544194

RESUMEN

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.


Asunto(s)
Adiponectina/genética , Diabetes Mellitus Tipo 2/etiología , Predisposición Genética a la Enfermedad , Resistencia a la Insulina/genética , Leptina/genética , Lipasa/genética , Proteínas de la Membrana/genética , Obesidad/complicaciones , Obesidad/genética , Adiponectina/sangre , Adulto , Femenino , Fibronectinas/sangre , Fibronectinas/genética , Marcadores Genéticos , Humanos , Leptina/sangre , Lipasa/sangre , Masculino , Proteínas de la Membrana/sangre , Polimorfismo Genético , Adulto Joven
20.
Arch Endocrinol Metab ; 64(3): 276-281, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32555994

RESUMEN

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.


Asunto(s)
Adiposidad/fisiología , Climaterio/sangre , Leptina/sangre , Adulto , Factores de Edad , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Climaterio/fisiología , Estudios de Cohortes , Femenino , Humanos , Persona de Mediana Edad , Factores Socioeconómicos
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA