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BACKGROUND: Vitamin D can influence more than 200 genes in various tissues showing its credibility among the fat-soluble vitamins. Vitamin D deficiency is directly proportional to major clinical conditions such as cardiovascular diseases, diabetes, malignancy, and multiple sclerosis. This study was conducted to determine the vitamin D level of individuals and its association with depression. METHODS: Vitamin D levels of 100 healthy and 100 depressed subjects were determined. The isolated subjects were screened on the Beck Depression Inventory (BDI) scale and divided into three groups according to their age. Group-I comprised subjects of age 20 years and below, Group-II included subjects of age 21 to 60, and Group-III comprised subjects of ≥ 61 years of age. A sufficient level of vitamin D in normal subjects was noted, while mild deficiency of vitamin D status was observed in depressed subjects. RESULTS: Our study has reported a higher percentage of vitamin D deficiency in the Peshawar region. The results of our study indicated that depression was common in individuals having vitamin D deficiency. CONCLUSIONS: The study showed a very high frequency of vitamin D deficiency in subjects with depression in Peshawar, Pakistan. The deficiency of vitamin D was observed more in females as compared to males. Further studies should explicate whether the highly widespread vitamin D deficiency could be cost-effectively treated as part of preventive or treatment interventions for depression.
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BACKGROUND: Preeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology. The endothelial nitric oxide synthase (eNOS) gene and nitric oxide (NO) levels has been reported to be associated with PE predisposition in various populations. Therefore, present study was designed to investigate the role of NO levels and eNOS gene variants in preeclamptic women in Pakistan. METHODS: A total of 600 women were evaluated, 188 of PE with mild features, 112 of PE with severe features and 300 normotensive pregnant women. NO levels were detected by Greiss reaction method and genotyping following sequencing was conducted for eNOS gene variants. Further insilico studies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation. RESULTS: Reduced concentrations of NO were reported in all PE groups (p < 0.05) as compared to controls. The frequency of c.894 T (p.298Asp) and g.-786C alleles were significantly associated with PE. In addition, novel homozygous variant g.2051G > A was also significantly associated with PE when compared to normotensive women. Dynamic simulation studies revealed that Glu298Asp mutation destabilize the protein molecule and decrease the overall stability of eNOS protein. Molecular docking analysis of mutant promoter with transcription factors STAT3 and STAT6 proposed changes in protein regulation upon these reported mutations in upstream region of the gene. CONCLUSION: Considering the results of current study, the functional alterations induced by these variants may influence the bioavailability of NO and represents a genetic risk factor for increased susceptibility to PE. However, large studies or meta-analysis are necessary to validate these findings.
Preeclampsia (PE) is a complex pregnancy hypertensive disorder with multifaceted etiology characterized by increased hypertension and proteinuria after 20 weeks of gestation. The present study was directed to determine the role of eNOS in susceptibility to PE and the association of c.894G > T (p.(Glu298Asp), intron 4b/4a, g.-786 T > C and other possible variants of eNOS gene with preeclampsia in Pakistani population. Computational analysis of identified variants in the coding and non-coding region of the eNOS gene was also conducted to determine the change in gene regulation and further protein stability. A total of 600 women were evaluated, 188 with mild and 112 with PE with severe features PE with 300 normotensive pregnant women. NO levels and genotyping following sequencing was conducted for eNOS gene variants. Further insilico studies were performed to get insights into the structural and functional impact of identifies mutation on eNOS protein as well as on protein regulation. Data from the current study suggest that there might be other risk variants of the eNOS gene (g.2051G > A and g.1861G > A) and lower levels of serum NO that confers in an increased risk of PE. The detailed computational investigation further confirmed the deformities and changes in protein flexibility upon Glu298Asp. These structural alterations might be associated with preeclampsia. Variants in the promoter region of the eNOS gene further validate the change in gene regulation for the onset of disease. Identification of key structural and functional features in eNOS protein and gene regulatory region might be used for designing specific drugs for therapeutic purpose.
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Óxido Nítrico Sintase Tipo III , Pré-Eclâmpsia , Estudos de Casos e Controles , Feminino , Genótipo , Humanos , Simulação de Acoplamento Molecular , Óxido Nítrico Sintase Tipo III/genética , Paquistão , Pré-Eclâmpsia/genética , GravidezRESUMO
Cisplatin is an efficient anticancer drug against various types of cancers however, its usage involves side effects. We investigated the mechanisms of action of indole derivative, 2-(5-methoxy-2-methyl-1H-indol-3-yl)-N'-[(E)-(3-nitrophenyl) methylidene] acetohydrazide (MMINA) against anticancer drug (cisplatin) induced organ damage using a rodent model. MMINA treatment reversed Cisplatin-induced NO and malondialdehyde (MDA) augmentation while boosted the activity of glutathione peroxidase (GPx), and superoxide dismutase (SOD). The animals were divided into five groups (n = 7). Group1: Control (Normal) group, Group 2: DMSO group, Group 3: cisplatin group, Group 4: cisplatin + MMINA group, Group 5: MMINA group. MMINA treatment normalized plasma levels of biochemical enzymes. We observed a significant decrease in CD4+COX-2, STAT3, and TNF-α cell population in whole blood after MMINA dosage. MMINA downregulated the expression of various signal transduction pathways regulating the genes involved in inflammation i.e. NF-κB, STAT-3, IL-1, COX-2, iNOS, and TNF-α. The protein expression of these regulatory factors was also downregulated in the liver, kidney, heart, and brain. In silico docking and dynamic simulations data were in agreement with the experimental findings. The physiochemical properties of MMINA predicted it as a good drug-like molecule and its mechanism of action is predictably through inhibition of ROS and inflammation.
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Antineoplásicos/efeitos adversos , Antioxidantes/administração & dosagem , Antioxidantes/farmacocinética , Cisplatino/efeitos adversos , Indóis/administração & dosagem , Indóis/farmacocinética , Simulação de Acoplamento Molecular , Animais , Antineoplásicos/administração & dosagem , Antioxidantes/química , Cisplatino/administração & dosagem , Glutationa Peroxidase/metabolismo , Indóis/química , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Malondialdeído/metabolismo , Modelos Animais , Óxido Nítrico/metabolismo , Estresse Oxidativo/efeitos dos fármacos , Ratos , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. METHODS: Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 µg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. RESULTS: Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 µg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. CONCLUSION: These results suggest that exposure to 5 and 50 µg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.
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Disruptores Endócrinos/toxicidade , Exposição Ambiental/efeitos adversos , Poluentes Ambientais/toxicidade , Sistema Hipotálamo-Hipofisário/efeitos dos fármacos , Infertilidade Masculina/induzido quimicamente , Fenóis/toxicidade , Sulfonas/toxicidade , Testículo/efeitos dos fármacos , Animais , Biomarcadores , Sistema Hipotálamo-Hipofisário/metabolismo , Sistema Hipotálamo-Hipofisário/fisiopatologia , Infertilidade Masculina/metabolismo , Infertilidade Masculina/fisiopatologia , Masculino , Ratos , Ratos Sprague-Dawley , Testículo/metabolismo , Testículo/fisiopatologia , Testes de Toxicidade CrônicaRESUMO
AIMS/INTRODUCTION: This 6-month interventional study aimed to investigate the effectiveness of different educational programs among Saudi women with prediabetes referred by primary care. MATERIALS AND METHODS: A total of 253 (100 group education program [GEP], 84 WhatsApp education program [WEP] and 69 control group [CG]) eligible participants were invited to take part in the study, out of whom 120 received intervention (40 GEP, 43 WEP and 37 CG). GEP participants received focused, individualized lifestyle modification advice with bimonthly support sessions, WEP participants received the same intervention, but delivered through social media (WhatsApp). The CG received standard care. Anthropometrics, biochemical profiles and macronutrient intake were measured at baseline, and 3 and 6 months. The primary end-points were glycated hemoglobin and weight, with lipids and dietary changes as secondary outcomes. RESULTS: Glycated hemoglobin significantly improved in all groups post-intervention (GEP baseline 6.0 ± 0.2 vs 6 months 5.5 ± 0.54; P < 0.001, WEP 6.0 ± 0.26 vs 5.3 ± 0.51; P < 0.001, CG 6.0 ± 0.37 vs 5.7 ± 0.49; P < 0.001), but with no difference in between-group comparisons (P = 0.33). Within-group comparisons showed a reduction in weight, but only in the GEP group (90.6 kg ± 27.3 vs 84.8 kg ± 24.3; P < 0.01), and this was significant in between-group comparison (P = 0.003). Significant between-group comparisons with respect to energy (g) intake (P = 0.005) were also observed, as well as triglycerides (P < 0.001) and low-density lipoprotein cholesterol (P = 0.001), all in favor of the GEP group. CONCLUSIONS: Diabetes prevention programs, whether delivered through a focused educational group, social media or standard care, are equally efficacious in improving glycated hemoglobin levels among Saudi women with prediabetes, but a focused educational group was more effective in terms of successful weight loss.
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Educação de Pacientes como Assunto , Estado Pré-Diabético/terapia , Comportamento de Redução do Risco , Mídias Sociais , Adulto , Antropometria , Ingestão de Alimentos , Feminino , Hemoglobinas Glicadas/metabolismo , Humanos , Pessoa de Meia-Idade , Estado Pré-Diabético/sangue , Arábia SauditaRESUMO
Our study aimed to identify the new blood-based biomarkers for the diagnosis and prognosis of cervical cancer. Moreover, the three-dimensional (3D) structure of Kruppel-like factor 9 (KLF9) was also determined in order to better understand its function, and a signaling pathway was constructed to identity its upstream and downstream targets. In the current study, the co-expressions of tumor protein D52 (TPD52), KLF9, microRNA 223 (miR-223), and protein kinase C epsilon (PKCϵ) were evaluated in cervical cancer patients and a possible relation with disease outcome was revealed. The expressions of TPD52, KLF9, miR-223, and PKCϵ were studied in the blood of 100 cervical cancer patients and 100 healthy controls using real-time PCR. The 3D structure of KLF9 was determined through homology modeling via the SWISS-MODEL and assessed using the Ramachandran plot. The predicted 3D structure of KLF9 had a similarity index of 62% with its template (KLF4) with no bad bonds in it. In order to construct a genetic pathway, depicting the crosstalk between understudied genes, STRING analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG), and DAVID software were used. The constructed genetic pathway showed that all the understudied genes are linked to each other and involved in the PI3K/Akt signaling pathway. There was a 23-fold increase in TPD52 expression, a 2-fold increase in miR-223 expression, a 0.14-fold decrease in KLF9 expression, and a 0.05-fold decrease of PKCϵ expression in cervical cancer. In the present study, we observed an association of the expressions of TPD52, KLF9, miR-223, and PKCϵ with tumor stage, metastasis, and treatment status of cervical cancer patients. Elevated expressions of TPD52 and miR-223 and reduced expressions of KLF9 and PKCϵ in peripheral blood of cervical cancer patients may serve as predictors of disease diagnosis and prognosis. Nevertheless, further in vitro and tissue-level studies are required to strengthen their role as potential diagnostic and prognostic biomarkers.
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Dietary intake influences gut microbiota activity. Nevertheless, there is a lack of evidence available that illustrates the acute effects of high glucose meal on metabolic endotoxemia. The present study assessed the acute impact of high glucose meal on endotoxemia and other clinical parameters in Saudi females with varying degrees of glycemia.The subjects were 64 consenting pre-menopausal women, grouped into 3: control [nâ=â14 lean, non-T2DM, BMIâ=â22.2â±â2.2âkg/m]; overweight [nâ=â16, non-T2DM, BMIâ=â28.5â±â1.5âkg/m] and T2DM [nâ=â34, BMIâ=â35.2â±â7.7âkg/m]. After an overnight fast, all subjects were given a standardized high-glucose (75âg) meal. Anthropometrics were taken and blood samples were withdrawn at baseline and postprandial (0, 2 and 4-hours), serum glucose, endotoxin and lipid profile were quantified.At baseline, total cholesterol, LDL-cholesterol, triglycerides and serum glucose levels were significantly higher (P values <.01) whereas significantly lower HDL-cholesterol levels (Pâ<â.01) were observed in T2DM subjects compared to other groups. Baseline endotoxin levels were highest in the overweight group (3.2â±â1.1 mmol/L) as compared to control (2.0â±â0.5 mmol/L) and T2DM (2.7â±â1.2 mmol/L) (Pâ=â.046). HDL-cholesterol, LDL-cholesterol and triglycerides, significantly decreased in the T2DM group after 2âhours (P values <.05), whereas unremarkable changes observed in other groups. Lastly, endotoxin levels significantly increased only in the overweight group (3.2â±â1.1 vs 4.2â±â1.4 mmol/L; Pâ<â.05), 4âhours postprandial.High glucose meal elevates endotoxemia only among overweight subjects and impairs dysbiosis.
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Endotoxemia/complicações , Glucose/análise , Obesidade/complicações , Administração Oral , Adulto , Árabes/classificação , Árabes/estatística & dados numéricos , Índice de Massa Corporal , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/fisiopatologia , Endotoxemia/fisiopatologia , Jejum/sangue , Jejum/metabolismo , Feminino , Humanos , Lipídeos/análise , Lipídeos/sangue , Pessoa de Meia-Idade , Obesidade/fisiopatologia , Prevalência , Arábia SauditaRESUMO
Doxorubicin (DOX) is an anthracycline drug used for cancer treatment. However, its treatment is contiguous with toxic effects. We examined the nephroprotective potential of A. hydaspica polyphenol-rich ethyl acetate extract (AHE) against DOX persuaded nephrotoxicity. 36 male Sprague Dawley rats were randomly assorted into 6 groups. Control group received saline; DOX group: 3 mg/kg b.w. dosage of DOX intraperitoneally for 6 weeks (single dose/week). In co-treatment groups, 200 and 400 mg/kg b.w AHE was given orally for 6 weeks in concomitant with DOX (3 mg/kg b.w, i.p. injection per week) respectively. Standard group received silymarin 400 mg/kg b.w daily + DOX (single dose/week). Biochemical kidney function tests, oxidative stress markers, genotoxicity, antioxidant enzyme status, and histopathological changes were examined. DOX caused significant body weight loss and decrease kidney weight. DOX-induced marked deterioration in renal function indicators in both urine and serum, i.e., PH, specific gravity, total protein, albumin, urea, creatinine, uric acid, globulin, blood urea nitrogen, etc. Also, DOX treatment increases renal tissue oxidative stress markers, while lower antioxidant enzymes in tissue along with degenerative alterations in the renal tissue compared to control rats. AHE co-treatment ameliorates DOX-prompted changes in serum and urine chemistry. Likewise, AHE treatment decreases sensitive markers of oxidative stress and prevented DNA damages by enhancing antioxidant enzyme levels. DOX induction in rats also caused DNA fragmentation which was restored by AHE co-treatment. Moreover, the histological observations evidenced that AHE effectively rescued the kidney tissue from DOX interceded oxidative damage. Our results suggest that co-treatment of AHE markedly improve DOX-induced deleterious effects in a dose-dependent manner. The potency of AHE co-treatment at 400 mg/kg dose is similar to silymarin. These outcomes revealed that A. hydaspica AHE extract might serve as a potential adjuvant that avoids DOX-induced nephrotoxicity.
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Osteoporosis and osteopenia has a significant link with substantial fracture risk. Epidemiological data revealed a protective role of adipose tissue on bone biology in postmenopausal osteoporosis. The current study assessed the associations between select adipokines and bone mineral density (BMD) in postmenopausal women. A total of 175 Saudi postmenopausal women were selected and categorized based on their BMD (normal & low-BMD). Circulating levels of select adipokines (adiponectin, resistin, leptin, and adipsin), insulin, 25(OH)D and RANKl were determined using commercially available assay kits. BMD was measured by dual-energy X-ray absorptiometry (DXA). Overall and among low-BMD subjects, adiponectin consistently showed a significant inverse association with BMD (overall -0.34, pâ¯<â¯0.01; low BMD group -0.34, pâ¯<â¯0.01). In multiple regression, adiponectin (-0.29⯱â¯0.06, pâ¯<â¯0.00) and resistin (-0.08⯱â¯0.04, pâ¯<â¯0.05) were inversely significant with BMD overall, but after stratification the significance was lost for resistin (-0.05⯱â¯0.04, pâ¯<â¯0.224) whereas adiponectin remained (-0.22⯱â¯0.07, pâ¯<â¯0.02) in low-BMD subjects. Adipsin, leptin and lipocalin-2 showed no significant associations. Findings of the present study revealed that only adiponectin showed a significantly strong inverse association with low BMD, suggesting that insulin sensitivity may influence bone health in Arab postmenopausal women.
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Few evaluations of interventions to delay or prevent type 2 diabetes mellitus (T2DM) in Saudi Arabia (SA) have been undertaken. The present study evaluates the impact of a 6-month intensive lifestyle modification intervention delivered in primary care. Females from SA with prediabetes, aged 18-55 years, were recruited with 190 participants eligible following screening and randomly allocated to receive a 3-month one-on-one, intensive lifestyle modification (intervention group (IG) n = 95) or standard guidance (control group (CG) n = 95). Participants completed questionnaires including demographic, dietary and physical activity data. Blood samples were collected at baseline, 3 and 6 months. A total of 123 (74 IG (age 40.6 ± 9.8 years; body mass index (BMI) 31.2 ± 7.0 kg/m2) and 49 CG (age 40.6 ± 12.7 years; BMI 32.3 ± 5.4 kg/m2)) participants completed the study. After 6 months, haemoglobin A1c (HbA1c; primary endpoint) significantly improved in the IG than CG completers in between-group comparisons (p < 0.001). Comparison between groups showed significant improvements in overall energy intake, total and high density lipoprotein (HDL)-cholesterol in favour of IG (p-values < 0.001, 0.04 and <0.001, respectively). BMI and weight change were not clinically significant in between group comparisons. A 6-month, intense one-on-one intervention in lifestyle modification significantly improves glycaemic and cardio metabolic profile of females living in SA with pre-diabetes delivered in a primary care setting. Longer duration studies, using the same intervention, may determine whether a meaningful weight loss secondary to improved diet can be achieved.
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Educação de Pacientes como Assunto/métodos , Estado Pré-Diabético/epidemiologia , Estado Pré-Diabético/terapia , Adolescente , Adulto , Árabes , Glicemia , Exercício Físico , Feminino , Humanos , Pessoa de Meia-Idade , Sobrepeso , Arábia Saudita/epidemiologia , Redução de Peso , Adulto JovemRESUMO
OBJECTIVE: The present single-center observational study determined the prevalence and coexistence of sarcopenia, pre-sarcopenia, and metabolic syndrome (MetS) among apparently healthy Arab men and whether having both conditions present a unique cardiometabolic profile that is distinct than having the conditions separately. METHODS: A total of 471 out of 530 Arab men aged 20-77 years old were included after screening for the presence of pre-sarcopenia (ALM/ht2 < 7.26 kg/m2), sarcopenia (presence of both low muscle mass and low function), and MetS. MetS screening was done using the definition by the NCEP-ATP III. Based on the screening results, the participants were classified as control (normal) group (N = 328), MetS only (N = 73), pre-sarcopenia only (N = 64), and MetS + pre-sarcopenia (N = 6). RESULTS: Pre-sarcopenia without MetS was observed in 64 participants (13.6%), while MetS without pre-sarcopenia was observed in 73 participants (15.5%). MetS + pre-sarcopenia was observed only in 6 participants (1.3%). None of the participants had sarcopenia. Age- and BMI-adjusted comparisons showed that those with MetS + pre-sarcopenia had the highest diastolic blood pressure and triglyceride levels as compared to all groups (p values < 0.001). MetS + pre-sarcopenia group also had the highest levels of glucose and the lowest lean arms-legs/BMI ratio than control and pre-sarcopenia groups (p values < 0.001 and 0.005, respectively). CONCLUSION: The prevalence of pre-sarcopenia + MetS is low among young adult Arab men, but shows a unique cardiometabolic profile that is worse than those having only one of the conditions. Further investigations should be done among Arab women and the elderly.
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Árabes/estatística & dados numéricos , Síndrome Metabólica/complicações , Síndrome Metabólica/epidemiologia , Sintomas Prodrômicos , Sarcopenia/complicações , Sarcopenia/epidemiologia , Adulto , Idoso , Composição Corporal/fisiologia , Densidade Óssea , Comorbidade , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-Idade , Prevalência , Sarcopenia/diagnóstico , Sarcopenia/patologia , Arábia Saudita/epidemiologia , Adulto JovemRESUMO
This study determined the effects of a high-fat meal on circulating endotoxin and cardiometabolic indices in adult Arab women. The cohort consisted of 92 consenting Saudi women (18 non-diabetic (ND)) control subjects; Age 24.4 ± 7.9 year; body mass index (BMI) 22.2 ± 2.2 Kg/m2), 24 overweight/obese (referred to as overweight-plus (overweight+)) subjects (Age 32.0 ± 7.8 year; BMI 28.5 ± 1.5 Kg/m2) and 50 type 2 diabetes mellitus (T2DM) patients (Age 41.5 ± 6.2 year; BMI 35.2 ± 7.7 Kg/m2). All were given a high-fat meal (standardized meal: 75 g fat, 5 g carbohydrate, 6 g protein) after an overnight fast of 12-14 h. Anthropometrics were obtained and fasting blood glucose, lipids, and endotoxin were serially measured for four consecutive postprandial hours. Endotoxin levels were significantly elevated prior to a high-fat meal in the overweight+ and T2DM than the controls (p < 0.05). Furthermore, the postprandial cardiometabolic changes led to a more detrimental risk profile in T2DM subjects than other groups, with serial changes most notable in glucose, triglycerides, high density lipoprotein-cholesterol (HDL-cholesterol), and insulin levels (p-values < 0.05). The same single meal given to subjects with different metabolic states had varying impacts on cardiometabolic health. Endotoxemia is exacerbated by a high-fat meal in Arab subjects with T2DM, accompanied by a parallel increase in cardiometabolic risk profile, suggesting disparity in disease pathogenesis of those with or without T2DM through the altered cardiometabolic risk profile rather than variance in metabolic endotoxinaemia with a high-fat meal.
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Diabetes Mellitus Tipo 2/sangue , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/efeitos adversos , Endotoxemia , Resistência à Insulina , Obesidade/sangue , Período Pós-Prandial , Adolescente , Adulto , Árabes , Glicemia/metabolismo , Índice de Massa Corporal , HDL-Colesterol/sangue , Diabetes Mellitus Tipo 2/complicações , Gorduras na Dieta/administração & dosagem , Endotoxemia/etiologia , Endotoxinas , Jejum , Feminino , Humanos , Insulina/sangue , Refeições , Pessoa de Meia-Idade , Obesidade/complicações , Arábia Saudita , Triglicerídeos/sangue , Adulto JovemRESUMO
OBJECTIVE: Central obesity and sub-clinical inflammation increase metabolic risk, this study examined the intracellular inflammatory pathways in adipose tissue (AT) that contribute to this risk. DESIGN AND METHODS: This study therefore addressed the influence of NFκB and JNK activation in human abdominal subcutaneous (AbdSc) and omental (Om) AT, the effect of adiposity, T2DM status and the role of TNFα in vitro, using molecular biology techniques. RESULTS: Our data showed NFκB activity is increased in Om AT versus AbdSc AT (P<0.01), which was reversed with respect to depot specific activation of JNK (P<0.01). However, T2DM status appeared to preferentially activate NFκB (P<0.001) over JNK. Furthermore, in vitro studies showed recombinant human (rh) TNFα treated AbdSc adipocytes increased NFκB activity over time (2-48 h, P<0.05) whilst JNK activity reduced (2 h, 4 h, P<0.05); inhibitor studies supported a preferential role for NFκB as a modulator of TNFα secretion. CONCLUSIONS: These studies suggest distinct changes in NFκB and JNK activation, dependent upon AT depot, adiposity and T2DM status, with in vitro use of rh TNFα leading to activation of NFκB. Consequently NFκB appears to play a central role in inflammatory mediated metabolic disease over JNK, highlighting NFκB as a potential key target for therapeutic intervention.
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Tecido Adiposo/metabolismo , Adiposidade/fisiologia , Diabetes Mellitus Tipo 2/genética , NF-kappa B/fisiologia , Paniculite/genética , Fator de Necrose Tumoral alfa/fisiologia , Tecido Adiposo/imunologia , Tecido Adiposo/patologia , Adulto , Idoso , Células Cultivadas , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Feminino , Humanos , Inflamação/genética , Inflamação/metabolismo , Masculino , Pessoa de Meia-Idade , Proteína Quinase 8 Ativada por Mitógeno/genética , Proteína Quinase 8 Ativada por Mitógeno/metabolismo , Proteína Quinase 9 Ativada por Mitógeno/genética , Proteína Quinase 9 Ativada por Mitógeno/metabolismo , Paniculite/metabolismo , Proteínas Recombinantes/farmacologia , Fator de Necrose Tumoral alfa/farmacologiaRESUMO
OA (osteoarthritis) is a degenerative condition associated with obesity. A number of metabolic explanations have been proposed to explain the association between obesity and OA in non-weight-bearing joints; however, none of these hypotheses have been demonstrated empirically. In the present Hypothesis article, we recognize that obesity is associated with compromised gut mucosa, translocation of microbiota and raised serum LPS (lipopolysaccharide). The consequent activation of the innate immune response leads to increased serum titres of inflammatory mediators in obese patients, with both local and systemic markers of inflammation associated with onset and progression of OA. Furthermore, a number of workers have shown that articular cartilage repair is impaired by a range of inflammatory mediators, both in vitro and in vivo. We propose that metabolic endotoxaemia, caused by impaired gastric mucosa and low-grade chronic inflammation, may contribute to the onset and progression of OA in obese patients. This may account for the association between obesity and OA at non-weight-bearing joints which cannot be explained by biomechanical factors.
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Endotoxemia/complicações , Obesidade/complicações , Osteoartrite/etiologia , Translocação Bacteriana , Fenômenos Biomecânicos , Cartilagem Articular/metabolismo , Cartilagem Articular/patologia , Cartilagem Articular/fisiopatologia , Endotoxemia/sangue , Endotoxemia/fisiopatologia , Humanos , Inflamação/sangue , Inflamação/complicações , Inflamação/fisiopatologia , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Mucosa Intestinal/metabolismo , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Lipopolissacarídeos/sangue , Modelos Biológicos , Obesidade/sangue , Obesidade/fisiopatologia , Osteoartrite/sangue , Osteoartrite/fisiopatologia , Fatores de Risco , Suporte de CargaRESUMO
Understanding the interplay between sleep duration and quality, diet and hormones of obesity may help design effective lifestyle intervention strategies. Here we studied such associations in lean and obese teen-aged Saudi girls. In this cross-sectional observational study, 126 girls (62 lean and 64 obese) aged 14 -18 years (16.5 ± 1.5) were evaluated. A general questionnaire, which included sleep and diet questions, was obtained and anthropometric measurements and overnight fasting blood samples for determination of glucose, lipid profile and serum levels of leptin, adiponectin, resistin and ghrelin were collected. Subjects that slept < 5 hours/day had a higher percent of carbohydrate intake (p = 0.04) than those who slept > 7 hours/day. Adiponectin levels were higher in the lean than the obese group and increased in proportion to hours of sleep. Ghrelin had an inverse association with subjective sleep duration (p = 0.04), while resistin levels were directly proportional to it. Thus, the duration and quality of sleep influenced diet composition and the circulating levels of adipocytokines and ghrelin in adolescent girls. Long and uninterrupted sleep was associated with a better diet and a more favorable hormonal profile.