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1.
Artigo em Inglês | MEDLINE | ID: mdl-36244591

RESUMO

The Characidae family of fish is composed of commercially important species for which little is known about the regulation of feeding. Fish are ectotherms so that their body temperature fluctuates with the temperature of the surrounding water. Changes in water temperature can thus have major effects on the physiology of fish, in particular their feeding. The mechanisms by which appetite is influenced by changes in temperatures in fish remain unclear. In this study, we examined the effects of temperature on feeding behavior, food intake and the expression of appetite regulators in three characid fish (black tetra, neon tetra and cavefish) by submitting them to four different temperatures for 2 weeks (20°C, 24°C, 28°C, 32°C). In all species, food intake increased with increasing temperature. In neon and black tetras, increasing temperatures decreased expressions of orexin and leptin and increased that of cocaine and amphetamine regulated transcript (CART). In cavefish, temperature had no effect on brain orexin, leptin or CART. In all three species, higher temperatures induced increases in intestine expression of cholecystokinin (CCK), but no effects were seen for intestine ghrelin and peptide YY expressions. Our results show that temperature affects feeding in Characidae fish and induces species-specific changes in the expression of appetite regulators.


Assuntos
Apetite , Characidae , Animais , Apetite/fisiologia , Characidae/fisiologia , Orexinas/metabolismo , Leptina/farmacologia , Temperatura , Neônio/farmacologia , Ingestão de Alimentos , Água
2.
J Phys Chem B ; 126(44): 8970-8984, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36318704

RESUMO

Field-free capillary vibrating sharp-edge spray ionization (cVSSI) is evaluated for its ability to conduct native mass spectrometry (MS) experiments. The charge state distributions for nine globular proteins are compared using field-free cVSSI, field-enabled cVSSI, and electrospray ionization (ESI). In general, for both positive and negative ion mode, the average charge state (qavg) increases for field-free cVSSI with increasing molecular weight similar to ESI. A clear difference is that the qavg is significantly lower for field-free conditions in both analyses. Two proteins, leptin and thioredoxin, exhibit bimodal charge state distributions (CSDs) upon the application of voltage in positive ion mode; only a monomodal distribution is observed for field-free conditions. In negative ion mode, thioredoxin exhibits a multimodal CSD upon the addition of voltage to cVSSI. Extensive molecular dynamics (MD) simulations of myoglobin and leptin in nanodroplets suggest that the multimodal CSD for leptin may originate from increased conformational "breathing" (decreased packing) and association with the droplet surface. These properties along with increased droplet charge appear to play critical roles in shifting ionization processes for some proteins. Further exploration and development of field-free cVSSI as a new ionization source for native MS especially as applied to more flexible biomolecular species is warranted.


Assuntos
Leptina , Espectrometria de Massas por Ionização por Electrospray , Espectrometria de Massas por Ionização por Electrospray/métodos , Íons/química , Mioglobina/química , Tiorredoxinas
3.
Front Endocrinol (Lausanne) ; 13: 1042511, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36339447

RESUMO

Leptin has been found to be involved in the development and progression of many autoimmune diseases. As an organ-specific autoimmune disease, the pathogenesis of Hashimoto's thyroiditis has not been fully elucidated. It has been reported that serum leptin level is increased in Hashimoto's thyroiditis, but other studies have not shown any difference. We replicated a mouse model of experimental autoimmune thyroiditis (EAT) with a high-iodine diet and found that injection of the leptin receptor antagonist Allo-aca reduced thyroid follicle destruction and inflammatory cell infiltration in EAT mice, and thyroxine and thyroid autoimmune antibody levels. Further investigation revealed that Allo-aca promotes the differentiation of Treg cells and inhibits the differentiation of Th17 cells. We believe that Allo-aca can alter the differentiation of Treg/Th17 cells by inhibiting the leptin signaling pathway, thereby alleviating thyroid injury in EAT mice. Interfering with the leptin signaling pathway may be a novel new approach to treat treating and ameliorating Hashimoto's thyroiditis.


Assuntos
Doenças Autoimunes , Doença de Hashimoto , Tireoidite Autoimune , Camundongos , Animais , Tireoidite Autoimune/tratamento farmacológico , Células Th17/metabolismo , Células Th17/patologia , Leptina , Linfócitos T Reguladores , Receptores para Leptina , Doenças Autoimunes/metabolismo , Diferenciação Celular
4.
Nutrients ; 14(21)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36364860

RESUMO

BACKGROUND: Hypoxia is caused by the excessive expansion of the white adipose tissue (AT) and is associated with obesity-related conditions such as insulin resistance, inflammation, and oxidative stress. Docosahexaenoic acid (DHA) is an omega-3 fatty acid reported to have beneficial health effects. However, the effects of DHA in AT against hypoxia-induced immune-metabolic perturbations in adipocytes exposed to low O2 tension are not well known. Consequently, this study aimed to evaluate the impact of DHA on markers of inflammation, metabolism, apoptosis, and oxidative stress in 3T3-L1 cell adipocytes exposed to low O2 tension (1% O2) induced hypoxia. METHODS: The apoptosis and reactive oxygen species (ROS) rates were evaluated. Metabolic parameters such as lactate, FFA, glycerol release, glucose uptake, and ATP content were assessed by a fluorometer. The expression of HIF-1, GLUT1 and the secretion of adipocytokines such as leptin, adiponectin, and pro-inflammatory markers was evaluated. RESULTS: DHA-treated hypoxic cells showed significantly decreased basal free fatty acid release, lactate production, and enhanced glucose consumption. In addition, DHA-treatment of hypoxic cells caused a significant reduction in the apoptosis rate and ROS production with decreased lipid peroxidation. Moreover, DHA-treatment of hypoxic cells caused a decreased secretion of pro-inflammatory markers (IL-6, MCP-1) and leptin and increased adiponectin secretion compared with hypoxic cells. Furthermore, DHA-treatment of hypoxic cells caused significant reductions in the expression of genes related to hypoxia (HIF-1, HIF-2), anaerobic metabolism (GLUT1 and Ldha), ATP production (ANT2), and fat metabolism (FASN and PPARY). CONCLUSION: This study suggests that DHA can exert potential anti-obesity effects by reducing the secretion of inflammatory adipokines, oxidative stress, lipolysis, and apoptosis.


Assuntos
Ácidos Docosa-Hexaenoicos , Leptina , Camundongos , Animais , Células 3T3-L1 , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/metabolismo , Leptina/metabolismo , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Adiponectina/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Adipócitos , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Hipóxia/metabolismo , Obesidade/tratamento farmacológico , Obesidade/metabolismo , Adipocinas/metabolismo , Biomarcadores/metabolismo , Lactatos/metabolismo , Trifosfato de Adenosina/metabolismo
5.
Pediatr Int ; 64(1): e15183, 2022 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36348518

RESUMO

BACKGROUND: Knowledge of chronic kidney disease (CKD) with pubertal disorders (PD) in adolescent boys is limited as few studies have explored this disorder. This study aimed to identify the usefulness of assessing hormonal parameters in male adolescents with CKD and their correlation with PD in a 12-month follow-up period. METHODS: A prospective cohort study was conducted among male adolescents with CKD (stages IV and V). Data regarding the age at puberty onset were collected from the patients' clinical records and through interview. The patients were followed up for 12 months during their pubertal development. At the beginning, routine hormonal profile tests were performed to examine the patients' thyroid profile, prolactin levels, luteinizing hormone, follicle-stimulating hormone, testosterone, leptin, and receptor leptin. The hormonal profiles of patients with and without PD were compared. Comparisons between the groups were performed using the Student t-test and Fisher's exact tests. Logistic regression analysis was also performed. RESULTS: Data of 64 patients (26/64 with PD) were analyzed. The median age was 15 years and the median time for CKD evolution was 11 months. No differences between groups were noted in the general or biochemical characteristics of the patients. The hormonal parameters, prolactin levels were higher and the free leptin and free thyroxine levels were lower in patients with PD. Leptin receptor levels of >0.90 ng/mL (risk ratio [RR], 8.6; P = 0.004) and hyperprolactinemia (RR, 21.3; P = 0.049) were the risk factors for PD. CONCLUSIONS: Leptin receptor levels of >0.90 ng/mL and hyperprolactinemia are associated with the development of PD in male adolescents with CKD.


Assuntos
Hiperprolactinemia , Insuficiência Renal Crônica , Adolescente , Humanos , Masculino , Receptores para Leptina , Prolactina , Leptina , Hiperprolactinemia/complicações , Estudos Prospectivos , Puberdade , Insuficiência Renal Crônica/complicações
6.
Dis Markers ; 2022: 9539676, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36330203

RESUMO

Background: Heart failure with preserved ejection fraction (HFpEF) has a complex pathophysiology that encompasses systemic proinflammatory state and dysregulated levels of cardiometabolic and oxidative stress biomarkers. The prevalence of both HFpEF and atrial fibrillation (AF) is continuously rising, especially in the elderly. The aim of our study was to explore if there were any differences in biomarker levels and vascular function in the elderly patients with HFpEF with and without AF and to assess interconnections between clinically relevant biomarkers and cardiac and vascular function. Methods: This was a cross-sectional study of patients ≥ 65 years with HFpEF who were divided into 2 groups based on the presence or absence of AF. We have sonographically assessed echocardiographic parameters of left ventricular systolic and diastolic function and the peripheral vascular function parameters, namely, pulse wave velocity (PWV) and flow-mediated dilation (FMD). NT-proBNP, irisin, leptin, adiponectin, insulin-like growth factor 1 (IGF-1), and malondialdehyde (MDA) blood levels were determined. Results: Fifty-two patients (mean age 80 ± 7 years, 67% females) were included. Patients with HFpEF and AF had significantly lower levels of irisin (median 4.75 vs. 13.5 ng/mL, p = 0.007), leptin (median 9.5 vs. 15.0 ng/L, p = 0.023), and MDA (median 293 vs. 450 ng/mL, p = 0.017) and significantly higher values of NT-proBNP (median 2365 vs. 529 ng/L, p < 0.001) but not vascular function parameters, as compared to HFpEF patients without AF. MDA was significantly correlated with diastolic function (r = 0.395, p = 0.007) and FMD (r = 0.394, p = 0.011), while adiponectin was inversely associated with FMD (r = -0.325, p = 0.038) and left ventricular ejection fraction (r = -0.319, p = 0.029). Conclusions: Our results have demonstrated that patients with HFpEF and AF have significantly lower leptin, irisin, and MDA levels compared to patients with HFpEF but without AF. These results offer new insights into the complexity of vascular function and cardiometabolic and oxidative stress biomarkers in the context of HFpEF, AF, and aging.


Assuntos
Fibrilação Atrial , Insuficiência Cardíaca , Feminino , Humanos , Idoso , Idoso de 80 Anos ou mais , Masculino , Volume Sistólico/fisiologia , Função Ventricular Esquerda/fisiologia , Leptina , Estudos Transversais , Análise de Onda de Pulso , Adiponectina , Fibronectinas , Biomarcadores , Prognóstico
7.
Clin Lab ; 68(11)2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36377995

RESUMO

BACKGROUND: Obesity may also develop due to a viral infection caused by adenovirus 36. We aimed to detect the presence of neutralizing antibodies against Ad-36 in adult patients who developed type 2 diabetes due to obesity (BMI ≥ 30 kg/m2). METHODS: The patient group (PG) was composed of 80 obese people with type 2 diabetes, the patient control group (PCG) was composed of 40 non-obese people with type 2 diabetes, and the healthy control group (HCG) was com-posed of 40 non-obese people without type 1 or type 2 diabetes in this case-control study. The presence of Ad-36 neutralizing antibodies was studied by serum neutralization assay. RESULTS: A significant difference was found between the PG and HCG in terms of Ad-36 antibody positivity (p < 0.0001) but no significant difference was detected between the PG and the PCG (p > 0.05). BMI, serum leptin, adiponectin, and triglyceride levels were significantly higher in the PG (p < 0.05). Conversely, TNF-α and IL-6 levels were significantly lower in the PG (p < 0.0001). When the two groups were compared, the mean levels of total cho-lesterol and LDL in the PG were found to be high, although not significant (p > 0.05). In type 2 diabetes patients (n = 120), age, BMI, HDL, LDL, triglyceride, total cholesterol, Ad-36 presence, leptin, adiponectin, TNF-α, and IL-6 parameters were taken as independent variables for logistic regression. While BMIs was found to be significant (odds ration [OR] = 2.358; p = 0.0001, 95% Cl 1.507 - 3.690, Ad-36 presence was found to be a significant (OR = 27.352; p = 0.003, 95% Cl 3.157 - 236.961). Our study showed that BMI and Ad-36 increase type 2 diabetes risk by 2.3 and 27.3-fold in the PG and PCG (type 2 diabetes patients) versus the HCG. There was also a significant difference between PCG and HCG. CONCLUSIONS: We suggest that Ad-36 seropositivity is also a risk factor for the development of type 2 diabetes independent of being obese.


Assuntos
Infecções por Adenoviridae , Diabetes Mellitus Tipo 2 , Adulto , Humanos , Leptina , Adiponectina , Adenoviridae , Fator de Necrose Tumoral alfa , Diabetes Mellitus Tipo 2/complicações , Estudos de Casos e Controles , Interleucina-6 , Índice de Massa Corporal , Obesidade/complicações , Triglicerídeos , Anticorpos Neutralizantes
8.
Int J Mol Sci ; 23(21)2022 Oct 26.
Artigo em Inglês | MEDLINE | ID: mdl-36361728

RESUMO

Tumor extracellular vesicles (EVs), as endocytic vesicles able to transport nucleic acids, proteins, and metabolites in recipient cells, have been recognized fundamental mediators of cell-to-cell communication in breast cancer. The biogenesis and release of EVs are highly regulated processes and both the quantity of EVs and their molecular cargo might reflect the metabolic state of the producing cells. We recently demonstrated that the adipokine leptin, whose circulating levels correlate with adipose tissue expansion, is an inducer of EV release from breast cancer cells. Here, we show a specific proteomic signature of EVs released by MCF-7 breast cancer cells grown in the presence of leptin (Lep-EVs), in attempt to find additional molecular effectors linking obesity to breast cancer biology. An analysis of the proteomic profile of Lep-EVs by LC-MS/MS revealed a significant enrichment in biological processes, molecular functions, and cellular components mainly related to mitochondrial machineries and activity, compared to protein content of EVs from untreated breast cancer cells. Metabolic investigations, carried out to assess the autocrine effects of these vesicles on breast cancer cells, revealed that Lep-EVs were able to increase ATP levels in breast cancer cells. This result is associated with increased mitochondrial respiration evaluated by Seahorse analyzer, supporting the concept that Lep-EVs can modulate MCF-7 breast cancer cell oxidative metabolism. Moreover, taking into account the relevance of tumor immune cell crosstalk in the tumor microenvironment (TME), we analyzed the impact of these vesicles on macrophage polarization, the most abundant immune component in the breast TME. We found that tumor-derived Lep-EVs sustain the polarization of M0 macrophages, derived from the human THP-1 monocytic cells, into M2-like tumor-associated macrophages, in terms of metabolic features, phagocytic activity, and increased expression of CD206-positive population. Overall, our results indicate that leptin by inducing the release of EV-enriched in mitochondrial proteins may control the metabolism of MCF-7 breast cancer cells as well as that of macrophages. Characterization of tumor-derived EV protein cargo in an obesity-associated milieu, such as in the presence of elevated leptin levels, might allow identifying unique features and specific metabolic mechanisms useful to develop novel therapeutic approaches for treatment of breast cancer, especially in obese patients.


Assuntos
Neoplasias da Mama , Vesículas Extracelulares , Humanos , Feminino , Proteômica , Neoplasias da Mama/metabolismo , Leptina/metabolismo , Cromatografia Líquida , Espectrometria de Massas em Tandem , Vesículas Extracelulares/metabolismo , Obesidade/metabolismo , Microambiente Tumoral
9.
Sci Rep ; 12(1): 19573, 2022 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-36379980

RESUMO

Oocyte maturity is critical to the development potential of the embryo and pregnancy outcomes in natural and in-vitro fertilization (IVF). In IVF, oocyte maturity is typically evaluated using morphological criteria, although such assessment remains highly subjective. To identify reliable biomarkers of oocyte maturity, this study investigates the relationship between follicular cytokine concentrations and oocyte maturity in IVF patients with different ovarian reserves. In this prospective study, follicular fluid was collected during oocyte retrieval and the concentrations of cytokines involved in ovarian folliculogenesis were determined. Follicular fluid cytokine concentrations were compared between participants in three groups according to serum anti-Mullerian hormone (AMH) concentration, as follows: low AMH, < 2 ng/mL; normal AMH, 2-5 ng/mL; and high AMH, > 5 ng/mL. Pearson's correlation coefficient analysis showed that the number of mature oocytes correlated positively and strongly with serum AMH level (r = 0.719; p < 0.01). The leptin concentration in follicular fluid was significantly higher in women with normal AMH level than in those with low or high levels. ROC curve analysis showed that the follicular fluid levels of leptin (area under ROC curve, 0.829; 95% confidence interval, 0.659-0.998; p < 0.01) and SCF (area under ROC curve, 0.706; 95% confidence interval, 0.491-0.921; p = 0.087) were the best predictors of oocyte maturity. At an optimal cut-off value of 16 ng/mL, leptin had positive predictive value (sensitivity) up to 70% and negative predictive value (specificity) of 91% for indicating oocyte maturity. The concentration of leptin in follicular fluid is closely related to ovarian reserve and may serve as a biomarker to predict oocyte maturity.


Assuntos
Leptina , Oócitos , Gravidez , Humanos , Feminino , Estudos Prospectivos , Fertilização In Vitro , Líquido Folicular/química , Hormônio Antimülleriano , Fertilização , Biomarcadores , Citocinas
10.
Nutrients ; 14(21)2022 Nov 03.
Artigo em Inglês | MEDLINE | ID: mdl-36364892

RESUMO

This study aims to explore the effects of Garcinia mangostana (mangosteen) and Curcuma&nbsp;longa independently and synergistically in modulating induced inflammation and impaired brain neurotransmitters commonly observed in high-fat diet-induced obesity in rodent models. Male albino Wistar rats were divided into four experimental groups. Group I, control, obese, fed on a high-fat diet (HFD), and Group II-IV, fed on HFD then given mangosteen extract (400 mg/kg/day) and/or Curcuma (80 mg/kg/day), or a mixture of both for 6 weeks. Plasma pro-inflammatory cytokines, leptin, and brain serotonin, dopamine, and glutamate were measured in the five studied groups. G. mangostana and Curcuma longa extracts demonstrate antioxidant and DPPH radical scavenging activities. Both induced a significant reduction in the weight gained, concomitant with a non-significant decrease in the BMI (from 0.86 to 0.81 g/cm2). Curcuma either alone or in combination with MPE was more effective. Both extracts demonstrated anti-inflammatory effects and induced a significant reduction in levels of both IL-6 and IL-12. The lowest leptin level was achieved in the synergistically treated group, compared to independent treatments. Brain dopamine was the most affected variable, with significantly lower levels recorded in the Curcuma and synergistically treated groups than in the control group. Glutamate and serotonin levels were not affected significantly. The present study demonstrated that mangosteen pericarp extract (MPE) and Curcuma were independently and in combination effective in treating obesity-induced inflammation and demonstrating neuroprotective properties.


Assuntos
Garcinia mangostana , Animais , Masculino , Ratos , Encéfalo , Curcuma , Dieta Hiperlipídica , Dopamina , Garcinia mangostana/química , Glutamatos , Inflamação/tratamento farmacológico , Leptina , Neurotransmissores , Obesidade/tratamento farmacológico , Obesidade/etiologia , Extratos Vegetais/farmacologia , Extratos Vegetais/química , Ratos Wistar , Serotonina
11.
J Coll Physicians Surg Pak ; 32(11): 1410-1414, 2022 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-36377006

RESUMO

OBJECTIVE: To measure and compare serum levels of leptin and lipid profile parameters in primigravida women with PE and normotensive primigravida. STUDY DESIGN: Analytical cross-sectional study. PLACE AND DURATION OF STUDY: Department of Physiology and Cell Biology, University of Health Sciences, Lahore, from 2018 to 2020. METHODOLOGY: Preeclamptic (PE, group A) and normal primigravida (PG, group B) with gestational age 30-36 weeks were recruited from tertiary care hospitals. After written and informed consent, blood samples were taken. Serum was separated and stored at -80oC until processed. CBC and lipid profile of each patient was also done using automated lab machines. Serum levels of leptin were calculated by ELISA. The data was entered and analysed in SPSS version 20. RESULTS: The mean serum levels of leptin (ng/ml) in PE (group A) were significantly raised compared to normotensive PG (group B) at 33.44±12.91 and 4±6.20 respectively (p.


Assuntos
Hiperlipidemias , Pré-Eclâmpsia , Feminino , Humanos , Lactente , Estudos Transversais , Leptina , Lipídeos
12.
Yi Chuan ; 44(10): 950-957, 2022 Oct 20.
Artigo em Inglês | MEDLINE | ID: mdl-36384730

RESUMO

Adipose tissue plays an important role in metabolic physiology through energy storage and endocrine functions. Spatial transcriptomics is revealing the complexity of cell types and their interaction in the adipose tissue with regards to development, homeostasis and disease. Emerging evidence suggests the existence of different subtypes of mature adipocytes that may have distinct functions, the markers of which include leptin (LEP), adiponectin (ADIPOQ), perilipin-1/4 (PLIN), and serum amyloid A (SAA), marking different adipocyte subtypes. Currently, Adipoq-Cre is widely used to study adipocyte biology, however, there is no Cre line that specifically targets LEP+ adipocytes. Here, we report the construction and validation of a Lep-Cre mouse line, which has the endogenous Lep gene edited by the CRISPR-Cas9 technology to generate the Lep-peptide 2A (P2A)-Cre fusion gene. P2A induces an auto-hydrolysis of the fusion protein, leading to expression of the Cre recombinase by the Lep gene activity. The activity of Lep-Cre in different depots of adipose tissues and non-adipose tissues was visualized by the immunofluorescence microscopy in the Lep-Cre Rosa26-loxP-Stop-loxP-tdTomato mice. We showed that Lep-Cre marked white/beige adipose depots extensively, followed by brown adipose depots. Leaky activity was observed in varying degrees among peripheral organs but not in the paraventricular nucleus of the hypothalamus. In summary, we have constructed a new adipocyte-targeting Cre mouse line that would be useful to study the development and physiology of LEP+ adipocytes.


Assuntos
Adipócitos , Leptina , Camundongos , Animais , Leptina/genética , Leptina/metabolismo , Adipócitos/metabolismo , Integrases/genética , Integrases/metabolismo , Transgenes
13.
Vopr Pitan ; 91(5): 43-55, 2022.
Artigo em Russo | MEDLINE | ID: mdl-36394928

RESUMO

Extracts from bilberry leaves and blueberries containing a wide range of biologically active compounds, including polyphenols, are of particular interest due to their antioxidant, hypoglycemic and hypolipidemic properties. In this regard, The aim of this research was to investigate in vivo the effect of a concentrate of blueberrie polyphenolic compounds with buckwheat flour on some physiological and biochemical parameters in C57Bl/6 mice with impaired carbohydrate and lipid metabolism induced by the consumption of a high fat high carbohydrate (HFHC) diet. Material and methods. The polyphenol concentrate was obtained by sorption of blueberry extract on grinded buckwheat flour. Total polyphenol content was determined by Folin-Ciocalteu method, profiles of anthocyanins, flavonoids and easily digested carbohydrates were determined by HPLC. An in vivo experiment was carried out using 84 male mice C57Bl/6 for 109 days. Animals were divided into 3 groups: control fed standard semisynthetic diet, control treated with HFHC diet and experimental group treated with HFHC diet with addition of blueberry polyphenol concentrate (60 mg-eq. of gallic acid/kg body weight). Food intake, body weight gain and fasting blood glucose levels were measured during the experiment. Grip strength of the front paws of the animals was measured weekly. Oral glucose tolerance and insulin resistance tests were carried out twice. Common physiological tests (Elevated Plus Maze and Passive Avoidance Test) were used to assess the anxiety and memory of animals. Glycated hemoglobin level was determined in blood, plasma was collected for leptin and insulin level determination. The hepatic levels of triglycerides and cholesterol were assessed. Results. The concentrate of polyphenols extracted from blueberries and sorbed on grinded buckwheat flour was obtained under conditions that made it possible to exclude the sorption of easily digested carbohydrates - glucose, fructose and sucrose on the flour. The total concentrate content of polyphenols was 65.5±0.7 mg-eq. gallic acid/g, anthocyanins - 27.3±2.7 mg/g, flavonoids - 1.2±0.1 mg/g. The consumption of the concentrate by C57Bl/6 male mice with carbohydrate and lipid metabolism disorders induced by a HFHC diet had a significant (p<0.05) hypoglycemic and hypolipidemic effect, reducing the area under the curve in the insulin resistance test by 5.7% and decreasing the insulin and leptin levels by 31.3 and 15.9%, respectively (relative to the animals of comparison group fed HFHC diet). The consumption of the concentrate had a significant (p<0.05) anxiolytic effect, reducing the anxiety of animals by 2.2 times, as determined in the Elevated Plus Maze test. Conclusion. The results of the study indicate the prospects for using the developed blueberry polyphenol concentrate adsorbed on buckwheat flour as part of specialized foods for the prevention of such alimentary dependent diseases as metabolic syndrome, obesity, and diabetes mellitus.


Assuntos
Mirtilos Azuis (Planta) , Fagopyrum , Ingredientes de Alimentos , Resistência à Insulina , Insulinas , Masculino , Camundongos , Animais , Polifenóis/farmacologia , Polifenóis/química , Mirtilos Azuis (Planta)/química , Antocianinas , Leptina , Hipoglicemiantes/química , Obesidade , Ácido Gálico , Camundongos Endogâmicos C57BL
14.
Acta Clin Croat ; 61(1): 79-85, 2022 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36398078

RESUMO

Leptin is a polypeptide which is mostly produced in white fat tissue and is an important proinflammatory, proangiogenic, proinvasive and mitotic factor. There is ever more evidence suggesting the key role of leptin in the occurrence of breast cancer. The aim of the study was to investigate serum leptin levels in patients with benign breast tumors, as well as in various breast cancer phenotypes, taking into account leptin levels connected to menopausal status and body mass index (BMI). The study included 97 patients having their breast tumor surgically removed. Serum leptin level was determined by ELISA method in all study patients. Study results showed that significantly more women, regardless of having malignant or benign tumors, were postmenopausal and had a significantly higher level of leptin compared to the premenopausal group. The highest level of leptin was recorded in the group of postmenopausal obese women compared to other postmenopausal women but also compared to premenopausal women. According to BMI alone, obese women had a significantly higher level of leptin regardless of the type of tumor. The most significant differences in leptin levels observed through BMI were found in the Luminal B1 group. In conclusion, serum leptin level was shown to be a good diagnostic parameter suggesting a higher possibility of breast cancer development.


Assuntos
Neoplasias da Mama , Leptina , Feminino , Humanos , Pós-Menopausa , Pré-Menopausa , Obesidade/complicações
15.
Alzheimers Res Ther ; 14(1): 165, 2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36329496

RESUMO

BACKGROUND: Blood adiponectin and leptin are adipokines that emerged as potential biomarkers for predicting Alzheimer's disease (AD) owing to their strong connection with obesity. Although obesity affects the relation between beta-amyloid (Aß) aggregation and cognitive decline, the longitudinal interactive effect of adipokines and Aß on cognition and brain structures in humans remains unexplored. Hence, we investigated whether plasma levels of adiponectin and leptin are associated with future cognitive decline and cortical thinning across Aß conditions (Aß [+] and Aß [-]) in individuals with mild cognitive impairment (MCI). METHODS: Of 156 participants with MCI from the longitudinal cohort study of Alzheimer's Disease Neuroimaging Initiative (ADNI), 31 were Aß (-) and 125 were Aß (+) as determined by CSF analysis. The Alzheimer's Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores and the thickness of the parahippocampal and entorhinal cortices were used to evaluate cognition and brain structure, respectively. After stratifying groups by Aß conditions, the association of cognitive and brain structural changes with baseline plasma levels of adiponectin and leptin was examined. RESULTS: Of the total 156 participants, 51 were women (32.7%). The mean age of participants was 74.5 (standard deviation 7.57), and the mean follow-up period was 54.3 months, without a difference between the Aß (+) and (-) groups. After adjustment for confounders, higher plasma adiponectin levels were associated with a faster increase in ADAS-Cog scores, indicating faster cognitive decline under the Aß (+) condition (beta = 0.224, p = 0.018). Likewise, participants with higher plasma adiponectin presented faster cortical thinning in the bilateral parahippocampal cortices under the Aß (+) condition (beta = - 0.004, p = 0.012 for the right side; beta = - 0.004, p = 0.025 for the left side). Interestingly, plasma adiponectin levels were not associated with longitudinal ADAS-Cog scores or cortical thickness in the Aß (-) condition. Plasma leptin levels were not predictive of cognition or cortical thickness regardless of Aß status. CONCLUSION: Plasma adiponectin can be a potential biomarker for predicting the speed of AD progression in individuals with Aß (+) MCI.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Feminino , Humanos , Masculino , Peptídeos beta-Amiloides , Doença de Alzheimer/patologia , Adiponectina , Leptina , Afinamento Cortical Cerebral , Estudos Longitudinais , Disfunção Cognitiva/psicologia , Biomarcadores , Obesidade
16.
Nutrients ; 14(20)2022 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-36296907

RESUMO

BACKGROUND AND AIMS: Metabolic Associated Fatty Liver Disease (MAFLD) encompasses a spectrum of diseases from simple steatosis to nonalcoholic steatohepatitis (NASH). Here, we investigated the hepatoprotective role of Moringa oleifera aqueous extract on hepatic miRNAs, genes and protein expression, as well as histological and biochemical parameters in an experimental model of NASH. METHODS: Male C57BL/6J mice were fed with a high fat diet (HFD, 60% lipids, 42 gr/L sugar in water) for 16 weeks. Moringa extract was administered via gavage during the final 8 weeks. Insulin Tolerance Test (ITT) and HOMA-IR were calculated. Serum levels of insulin, resistin, leptin and PAI-1 and hepatic expression of miR-21a-5p, miR-103-3p, miR-122-5p, miR-34a-5p and SIRT1, AMPKα and SREBP1c protein were evaluated. Alpha-SMA immunohistochemistry and hematoxylin-eosin, Masson's trichrome and sirius red staining were made. Hepatic transcriptome was analyzed using microarrays. RESULTS: Animals treated with Moringa extract improved ITT and decreased SREBP1c hepatic protein, while SIRT1 increased. Hepatic expression of miR-21a-5p, miR-103-3p and miR-122-5p, miR34a-5p was downregulated. Hepatic histologic analysis showed in Moringa group (HF + MO) a significant decrease in inflammatory nodules, macro steatosis, fibrosis, collagen and αSMA reactivity. Analysis of hepatic transcriptome showed down expression of mRNAs implicated in DNA response to damage, endoplasmic reticulum stress, lipid biosynthesis and insulin resistance. Moringa reduced insulin resistance, de novo lipogenesis, hepatic inflammation and ER stress. CONCLUSIONS: Moringa prevented progression of liver damage in a model of NASH and improved biochemical, histological and hepatic expression of genes and miRNAs implicated in MAFLD/NASH development.


Assuntos
Resistência à Insulina , MicroRNAs , Moringa oleifera , Hepatopatia Gordurosa não Alcoólica , Extratos Vegetais , Animais , Masculino , Camundongos , Dieta Hiperlipídica/efeitos adversos , Epigênese Genética , Insulina/metabolismo , Leptina , Lipídeos , Fígado/metabolismo , Camundongos Endogâmicos C57BL , MicroRNAs/metabolismo , Moringa oleifera/química , Hepatopatia Gordurosa não Alcoólica/tratamento farmacológico , Hepatopatia Gordurosa não Alcoólica/etiologia , Inibidor 1 de Ativador de Plasminogênio/metabolismo , Resistina/metabolismo , Sirtuína 1/genética , Sirtuína 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Extratos Vegetais/farmacologia
17.
J Physiol Pharmacol ; 73(3)2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36302534

RESUMO

Vascular endothelial growth factor A (VEGF A) synthesis is intensified by leptin in: hypoxia-inducible factor 1 alpha (HIF-1A) and nuclear factor kappa-light-chain-enhancer of activated B cells (NfκB)-dependent manners. The study aimed to investigate the association between leptin and VEGF A serum levels in obese women with hyperglycaemia in the third trimester of pregnancy. Sixty obese pregnant women with hyperglycaemia were divided into groups according to body mass index (BMI): group 1: BMI 30.0-34.9 kg/m2; group 2: BMI 35.0-39.9 kg/m2; group 3: BMI ≥40 kg/m2. On the enrolment visit, waist circumference, body mass and height were measured. At visit 1 (V1; gestational week (GW) 28-32) and visit 2 (V2; GW 36-38), anthropometric, blood pressure and heart rate measurements, and blood sample collection were performed. Blood levels of leptin, VEGF A, VEGF receptor 2, HIF-1A, NfκB, interleukin 1 alpha, protein delta homolog 1, nitric oxide and glycated haemoglobin were determined. To analyse the predictors of the biochemical parametres involved in leptin and VEGF A cross-talk, multivariate logistic regression was implemented. Positive correlations between serum levels of leptin and VEGF A were found. Serum level of HIF-1A at V1 was a predictor for the highest quartile of the serum levels of VEGF A at V1 and V2. Leptin serum level at V1 was a predictor for the highest quartile of HIF-1A serum concentration at V2. In group 3 HIF-1A level was higher at V2 compared to V1. We conclude that in obese women with hyperglycaemia in the third trimester of pregnancy there is a significant positive influence of serum leptin on VEGF A synthesis and serum level and HIF-1A seems to play more important role in leptin and VEGF A cross-talk than NfκB.


Assuntos
Diabetes Gestacional , Hiperglicemia , Leptina , Obesidade , Fator A de Crescimento do Endotélio Vascular , Feminino , Humanos , Gravidez , Estudos de Coortes , Leptina/metabolismo , Obesidade/complicações , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
World J Pediatr Congenit Heart Surg ; 13(6): 745-751, 2022 11.
Artigo em Inglês | MEDLINE | ID: mdl-36300261

RESUMO

BACKGROUND: Failure to thrive (FTT), defined as weight or height less than the lowest 2.5 percentile for age, is prevalent in up to 66% of children with congenital heart disease (CHD). Risk stratification methods to identify those who would benefit from early intervention are currently lacking. We aimed to identify a novel growth biomarker to aid clinical decision-making in children with CHD. METHODS: This is a cross-sectional study of patients 2 months to 10 years of age with any CHD undergoing cardiac surgery. Preoperative weight-for-age Z scores (WAZ) and height-for-age Z scores (HAZ) were calculated and assessed for association with preoperative plasma biomarkers: growth differentiation factor 15 (GDF-15), fibroblast growth factor 21, leptin, prealbumin, and C-reactive protein (CRP). RESULTS: Of the 238 patients included, approximately 70% of patients had WAZ/HAZ < 0 and 34% had FTT. There was a moderate correlation between GDF-15 and WAZ/HAZ. When stratified by age, the correlation of GDF-15 to WAZ and HAZ was strongest in children under 2 years of age and persisted in the setting of inflammation (CRP > 0.5 mg/dL). Diagnoses commonly associated with congestive heart failure had high proportions of FTT and median GDF-15 levels. Prealbumin was not correlated with WAZ or HAZ. CONCLUSIONS: GDF-15 represents an important growth biomarker in children with CHD, especially those under 2 years of age who have diagnoses commonly associated with CHF. Our data do not support prealbumin as a long-term growth biomarker.


Assuntos
Fator 15 de Diferenciação de Crescimento , Cardiopatias Congênitas , Criança , Humanos , Lactente , Leptina , Estudos Transversais , Proteína C-Reativa , Cardiopatias Congênitas/cirurgia , Biomarcadores
19.
Front Endocrinol (Lausanne) ; 13: 1029376, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36313780

RESUMO

Purpose: A multifold association relates the hypothalamo-pituitary-thyroid axis to body weight. The potential underlying mechanisms are incompletely understood. Further, the mild severity of obesity and the small proportion of individuals with obesity in so far published cohort studies provide little insights on metabolic correlates of thyroid function in obesity. Methods: We retrospectively enrolled 5009 adults with obesity (F/M, 3448/1561; age range, 18-87 years; BMI range, 30.0-82.7 kg/m2), without known thyroid disease in a study on TSH and fT4 levels, lipid profile, glucose homeostasis and insulin resistance, anthropometric parameters including BIA-derived fat mass (%FM) and fat-free mass (FFM). Results: The overall reference interval for TSH in our obese cohort was 0.58-5.07 mIU/L. As subgroups, females and non-smokers showed higher TSH levels as compared to their counterparts (p<0.0001 for both), while fT4 values were comparable between groups. There was a significant upward trend for TSH levels across incremental BMI classes in females, while the opposite trend was seen for fT4 levels in males (p<0.0001 for both). Expectedly, TSH was associated with %FM and FFM (p<0,0001 for both). TSH and fT4 showed correlations with several metabolic variables, and both declined with aging (TSH, p<0.0001; fT4, p<0.01). In a subgroup undergoing leptin measurement, leptin levels were positively associated with TSH levels (p<0.01). At the multivariable regression analysis, in the group as a whole, smoking habit emerged as the main independent predictor of TSH (ß=-0.24, p<0.0001) and fT4 (ß=-0.25, p<0.0001) levels. In non-smokers, %FM (ß=0.08, p<0.0001) and age (ß=-0.05, p<0.001) were the main significant predictors of TSH levels. In the subset of nonsmokers having leptin measured, leptin emerged as the strongest predictor of TSH levels (ß=0.17, p<0.01). Conclusions: Our study provides evidence of a gender- and smoking-dependent regulation of TSH levels in obesity.


Assuntos
Leptina , Tireotropina , Adulto , Masculino , Feminino , Humanos , Adolescente , Adulto Jovem , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Índice de Massa Corporal , Estudos Retrospectivos , Obesidade , Estudos de Coortes
20.
Cell Metab ; 34(11): 1719-1731.e5, 2022 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-36220067

RESUMO

Recombinant human leptin (metreleptin) reduces hepatic lipid content in patients with lipodystrophy and overweight patients with non-alcoholic fatty liver disease and relative hypoleptinemia independent of its anorexic action. In rodents, leptin signaling in the brain increases very-low-density lipoprotein triglyceride (VLDL-TG) secretion and reduces hepatic lipid content via the vagus nerve. In this randomized, placebo-controlled crossover trial (EudraCT Nr. 2017-003014-22), we tested whether a comparable mechanism regulates hepatic lipid metabolism in humans. A single metreleptin injection stimulated hepatic VLDL-TG secretion (primary outcome) and reduced hepatic lipid content in fasted, lean men (n = 13, age range 20-38 years) but failed to do so in metabolically healthy liver transplant recipients (n = 9, age range 26-62 years) who represent a model for hepatic denervation. In an independent cohort of lean men (n = 10, age range 23-31 years), vagal stimulation by modified sham feeding replicated the effects of metreleptin on VLDL-TG secretion. Therefore, we propose that leptin has anti-steatotic properties that are independent of food intake by stimulating hepatic VLDL-TG export via a brain-vagus-liver axis.


Assuntos
Leptina , Hepatopatia Gordurosa não Alcoólica , Masculino , Humanos , Adulto Jovem , Adulto , Leptina/farmacologia , Leptina/metabolismo , Lipoproteínas VLDL/metabolismo , Triglicerídeos/metabolismo , Fígado/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Nervo Vago/metabolismo
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