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1.
PLoS One ; 15(9): e0237496, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32881912

RESUMO

BACKGROUND: Obesity is often associated with inflammation in adipose tissue (AT) with release of mediators of atherogenesis. We postulated that it would be feasible to collect sufficient abdominal AT to quantify changes in a broad array of adaptive and innate mononuclear white cells in obese non-diabetic adults in response to a dipeptidyl protease inhibitor (DPP4i), known to inhibit activation of immune white cells. METHODS: Adults 18-55 years-of-age were screened for abdominal obesity and insulin resistance or impaired glucose tolerance but without known inflammatory conditions. Twenty-one eligible participants consented for study and were randomized 3:1 to receive sitagliptin (DPP4i) at 100mg or matching placebo daily for 28 days. Abdominal AT collected by percutaneous biopsy and peripheral blood mononuclear cell fractions were evaluated before and after treatment; plasma was stored for batch testing. RESULTS: Highly sensitive C-reactive protein, a global marker of inflammation, was not elevated in the study population. Innate lymphoid cells (ILC) type 3 (ILC-3) in abdominal AT decreased with active treatment compared with placebo (p = 0.04). Other immune white cells in AT and peripheral blood mononuclear cell (PBMC) fractions did not change with treatment compared to placebo (p>0.05); although ILC-2 declined in PBMCs (p = 0.007) in the sitagliptin treatment group. Two circulating biomarkers of atherogenesis, interferon-inducible protein-10 (IP-10) and sCD40L declined in plasma (p = 0.02 and p = 0.07, respectively) in the active treatment group, providing indirect validation of a net reduction in inflammation. CONCLUSIONS: In this pilot study, two cell types of the innate lymphoid system, ILC-3 in AT and ILC-2 PBMCs declined during treatment and as did circulating biomarkers of atherogenesis. Changes in other immune cells were not demonstrable. The study showed that sufficient abdominal AT could be obtained to quantify white cells of both innate and adaptive immunity and to demonstrate changes during therapy with an immune inhibitor. TRIAL REGISTRATION: ClinicalTrials.gov identifier (NCT number): NCT02576.


Assuntos
Gordura Abdominal/patologia , Imunidade Inata , Leucócitos Mononucleares/patologia , Obesidade/imunologia , Adulto , Biomarcadores/sangue , Estudos de Viabilidade , Feminino , Citometria de Fluxo , Humanos , Linfócitos/patologia , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fosfato de Sitagliptina/farmacologia , Resultado do Tratamento
2.
PLoS One ; 15(8): e0237667, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32833960

RESUMO

BACKGROUND AND AIMS: This is the first time that obesity and diabetes mellitus (DM) as protein conformational diseases (PCD) are reported in children and they are typically diagnosed too late, when ß-cell damage is evident. Here we wanted to investigate the level of naturally-ocurring or real (not synthetic) oligomeric aggregates of the human islet amyloid polypeptide (hIAPP) that we called RIAO in sera of pediatric patients with obesity and diabetes. We aimed to reduce the gap between basic biomedical research, clinical practice-health decision making and to explore whether RIAO work as a potential biomarker of early ß-cell damage. MATERIALS AND METHODS: We performed a multicentric collaborative, cross-sectional, analytical, ambispective and blinded study; the RIAO from pretreated samples (PTS) of sera of 146 pediatric patients with obesity or DM and 16 healthy children, were isolated, measured by sound indirect ELISA with novel anti-hIAPP cytotoxic oligomers polyclonal antibody (MEX1). We carried out morphological and functional studied and cluster-clinical data driven analysis. RESULTS: We demonstrated by western blot, Transmission Electron Microscopy and cell viability experiments that RIAO circulate in the blood and can be measured by ELISA; are elevated in serum of childhood obesity and diabetes; are neurotoxics and works as biomarkers of early ß-cell failure. We explored the range of evidence-based medicine clusters that included the RIAO level, which allowed us to classify and stratify the obesity patients with high cardiometabolic risk. CONCLUSIONS: RIAO level increases as the number of complications rises; RIAOs > 3.35 µg/ml is a predictor of changes in the current indicators of ß-cell damage. We proposed a novel physio-pathological pathway and shows that PCD affect not only elderly patients but also children. Here we reduced the gap between basic biomedical research, clinical practice and health decision making.


Assuntos
Diabetes Mellitus Tipo 1/patologia , Diabetes Mellitus Tipo 2/patologia , Células Secretoras de Insulina/patologia , Polipeptídeo Amiloide das Ilhotas Pancreáticas/metabolismo , Obesidade/patologia , Estrutura Quaternária de Proteína , Adolescente , Animais , Linhagem Celular , Sobrevivência Celular , Células Cultivadas , Criança , Pré-Escolar , Estudos Transversais , Diabetes Mellitus Tipo 1/sangue , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/complicações , Humanos , Polipeptídeo Amiloide das Ilhotas Pancreáticas/sangue , Polipeptídeo Amiloide das Ilhotas Pancreáticas/toxicidade , Polipeptídeo Amiloide das Ilhotas Pancreáticas/ultraestrutura , Microscopia Eletrônica de Transmissão , Neurônios/efeitos dos fármacos , Obesidade/sangue , Obesidade/complicações , Projetos Piloto , Cultura Primária de Células , Multimerização Proteica , Ratos , Testes de Toxicidade Aguda
3.
PLoS One ; 15(8): e0237922, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32845924

RESUMO

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


Assuntos
Ritmo Circadiano/fisiologia , Jejum/sangue , Grelina/sangue , Hidrocortisona/sangue , Melatonina/sangue , Obesidade/sangue , Obesidade/fisiopatologia , Adulto , Dieta , Ingestão de Energia , Feminino , Hemodinâmica , Humanos , Leptina/sangue , Lipídeos/sangue , Masculino , Estudos Prospectivos , Sono/fisiologia
4.
Life Sci ; 258: 118204, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32763296

RESUMO

AIMS: Liver kinase B1 (LKB1) is a serine/threonine kinase. Although many biological functions of LKB1 have been identified, the role of hypothalamic LKB1 in the regulation of central energy metabolism and susceptibility to obesity is unknown. Therefore, we constructed POMC neuron-specific LKB1 knockout mice (PomcLkb1 KO) and studied it at the physiological, morphological, and molecular biology levels. MAIN METHODS: Eight-week-old male PomcLkb1 KO mice and their littermates were fed a standard chow fat diet (CFD) or a high-fat diet (HFD) for 3 months. Body weight and food intake were monitored. Dual-energy X-ray absorptiometry was used to measure the fat mass and lean mass. Glucose and insulin tolerance tests and serum biochemical markers were evaluated in the experimental mice. In addition, the levels of peripheral lipogenesis genes and central energy metabolism were measured. KEY FINDINGS: PomcLkb1 KO mice did not exhibit impairments under normal physiological conditions. After HFD intervention, the metabolic phenotype of the PomcLkb1 KO mice changed, manifesting as increased food intake and an enhanced obesity phenotype. More seriously, PomcLkb1 KO mice showed increased leptin resistance, worsened hypothalamic inflammation and reduced POMC neuronal expression. SIGNIFICANCE: We provide evidence that LKB1 in POMC neurons plays a significant role in regulating energy homeostasis. LKB1 in POMC neurons emerges as a target for therapeutic intervention against HFD-induced obesity and metabolic diseases.


Assuntos
Deleção de Genes , Neurônios/enzimologia , Obesidade/enzimologia , Pró-Opiomelanocortina/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Tecido Adiposo/patologia , Animais , Dieta Hiperlipídica , Epididimo/patologia , Comportamento Alimentar , Regulação da Expressão Gênica , Glucose/metabolismo , Hipotálamo/patologia , Inflamação/patologia , Leptina/metabolismo , Fígado/enzimologia , Fígado/patologia , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , NF-kappa B/metabolismo , Obesidade/sangue , Obesidade/patologia , Pró-Opiomelanocortina/genética , Ganho de Peso
5.
Life Sci ; 258: 118222, 2020 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-32768577

RESUMO

AIMS: We previously reported that fenugreek-derived 4-hydroxyisoleucine ameliorates insulin resistance via regulation of TNF-α converting enzyme (TACE) expression. In the present study, we further investigate the effects and mechanisms of fenugreek on obesity-induced inflammation and insulin signaling in the high-fat diet (HFD)-challenged obese mice. MAIN METHODS: After 12 weeks of HFD intervention, mice were treated with the low or high dosages of fenugreek. Serum levels of glucose, insulin, lipid profile, inflammation cytokines, and adipokines were detected. Macrophage infiltration and adipose tissue morphology were observed. Western blot was conducted to investigate the expressions of inactive rhomboid 2 (iRhom2) and TACE as well as other signaling pathways in subcutaneous adipose tissue. KEY FINDINGS: We showed that fenugreek significantly suppressed body weight gain and fat accumulation in HFD-challenged obese mice. Meanwhile, fasting glucose, insulin, and HOMA-IR in fenugreek-treated mice were remarkably decreased, which were properly explained by fenugreek-induced activation of the insulin receptor signaling pathway. Moreover, the anti-inflammatory properties of fenugreek were shown by the decrease of systemic and local expressions of pro-inflammatory cytokines as well as reduced macrophage infiltration into adipose tissue. Additionally, fenugreek markedly deactivated NF-κB and JNK pathways. Finally, we demonstrated that fenugreek strikingly repressed the transcriptions and expressions of iRhom2 and TACE. SIGNIFICANCE: Fenugreek shows an encouraging and promising property in ameliorating insulin resistance and suppressing inflammation in obesity, which might be realized by fenugreek-mediated inhibition of iRhom2/TACE axis-facilitated TNF-α release from adipocytes.


Assuntos
Proteína ADAM17/antagonistas & inibidores , Proteínas de Transporte/antagonistas & inibidores , Mediadores da Inflamação/antagonistas & inibidores , Resistência à Insulina/fisiologia , Obesidade/tratamento farmacológico , Trigonella , Proteína ADAM17/sangue , Animais , Proteínas de Transporte/sangue , Relação Dose-Resposta a Droga , Regulação para Baixo/efeitos dos fármacos , Regulação para Baixo/fisiologia , Inflamação/sangue , Inflamação/tratamento farmacológico , Mediadores da Inflamação/sangue , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/sangue , Extratos Vegetais/isolamento & purificação , Extratos Vegetais/farmacologia , Extratos Vegetais/uso terapêutico , Sementes
6.
PLoS Med ; 17(8): e1003232, 2020 08.
Artigo em Inglês | MEDLINE | ID: mdl-32764746

RESUMO

BACKGROUND: Obesity is closely related to the development of insulin resistance and type 2 diabetes (T2D). The prevention of T2D has become imperative to stem the rising rates of this disease. Weight loss is highly effective in preventing T2D; however, the at-risk pool is large, and a clinically meaningful metric for risk stratification to guide interventions remains a challenge. The objective of this study is to predict T2D risk using full-information continuous analysis of nationally sampled data from white and black American adults age ≥45 years. METHODS AND FINDINGS: A sample of 12,043 black (33%) and white individuals from a population-based cohort, REasons for Geographic And Racial Differences in Stroke (REGARDS) (enrolled 2003-2007), was observed through 2013-2016. The mean participant age was 63.12 ± 8.62 years, and 43.7% were male. Mean BMI was 28.55 ± 5.61 kg/m2. Risk factors for T2D regularly recorded in the primary care setting were used to evaluate future T2D risk using Bayesian logistic regression. External validation was performed using 9,710 participants (19% black) from Atherosclerotic Risk in Communities (ARIC) (enrolled 1987-1989), observed through 1996-1998. The mean participant age in this cohort was 53.86 ± 5.65 years, and 44.6% were male. Mean BMI was 27.15 ± 4.92 kg/m2. Predictive performance was assessed using the receiver operating characteristic (ROC) curves and area under the curve (AUC) statistics. The primary outcome was incident T2D. By 2016 in REGARDS, there were 1,602 incident cases of T2D. Risk factors used to predict T2D progression included age, sex, race, BMI, triglycerides, high-density lipoprotein, blood pressure, and blood glucose. The Bayesian logistic model (AUC = 0.79) outperformed the Framingham risk score (AUC = 0.76), the American Diabetes Association risk score (AUC = 0.64), and a cardiometabolic disease system (using Adult Treatment Panel III criteria) (AUC = 0.75). Validation in ARIC was robust (AUC = 0.85). Main limitations include the limited generalizability of the REGARDS sample to black and white, older Americans, and no time to diagnosis for T2D. CONCLUSIONS: Our results show that a Bayesian logistic model using full-information continuous predictors has high predictive discrimination, and can be used to quantify race- and sex-specific T2D risk, providing a new, powerful predictive tool. This tool can be used for T2D prevention efforts including weight loss therapy by allowing clinicians to target high-risk individuals in a manner that could be used to optimize outcomes.


Assuntos
Afro-Americanos , Interpretação Estatística de Dados , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/epidemiologia , Grupo com Ancestrais do Continente Europeu , Idoso , Idoso de 80 Anos ou mais , Teorema de Bayes , Glicemia/metabolismo , Estudos de Coortes , Diabetes Mellitus Tipo 2/diagnóstico , Feminino , Seguimentos , Humanos , Incidência , Resistência à Insulina/fisiologia , Modelos Logísticos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Valor Preditivo dos Testes , Reprodutibilidade dos Testes
7.
Food Chem Toxicol ; 145: 111701, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32858131

RESUMO

Obesity and its related metabolic disorders, as well as infectious diseases like covid-19, are important health risks nowadays. It was recently documented that long-term fasting improves metabolic health and enhanced the total antioxidant capacity. The present study investigated the influence of a 10-day fasting on markers of the redox status in 109 subjects. Reducing power, 2,2'-Azino-bis(3-ethylbenzothiazoline-6-sulfonic acid) diammonium salt radical cation(ABTS) radical scavenging capacity, and hydroxyl radical scavenging capacity increased significantly, and indicated an increase of circulating antioxidant levels. No differences were detected in superoxide scavenging capacity, protein carbonyls, and superoxide dismutase when measured at baseline and after 10 days of fasting. These findings were concomitant to a decrease in blood glucose, insulin, glycated hemoglobin (HbA1c), total cholesterol, low-density lipoprotein (LDL) and triglycerides as well as an increase in total cholesterol/high-density lipoprotein (HDL) ratio. In addition, the well-being index as well as the subjective energy levels increased, documenting a good tolerability. There was an interplay between redox and metabolic parameters since lipid peroxidation baseline levels (thiobarbituric acid reactive substances [TBARS]) affected the ability of long-term fasting to normalize lipid levels. A machine learning model showed that a combination of antioxidant parameters measured at baseline predicted the efficiency of the fasting regimen to decrease LDL levels. In conclusion, it was demonstrated that long-term fasting enhanced the endogenous production of antioxidant molecules, that act protectively against free radicals, and in parallel improved the metabolic health status. Our results suggest that the outcome of long-term fasting strategies could be depending on the baseline values of the antioxidative and metabolic status of subjects.


Assuntos
Jejum/metabolismo , Depuradores de Radicais Livres/metabolismo , Obesidade/dietoterapia , Estresse Oxidativo/fisiologia , Adolescente , Adulto , Idoso , Biomarcadores/sangue , Biomarcadores/metabolismo , Infecções por Coronavirus/prevenção & controle , Feminino , Humanos , Metabolismo dos Lipídeos/fisiologia , Peroxidação de Lipídeos/fisiologia , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/metabolismo , Pandemias/prevenção & controle , Pneumonia Viral/prevenção & controle , Adulto Jovem
8.
PLoS One ; 15(8): e0237708, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32817646

RESUMO

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


Assuntos
Hipertensão/sangue , Leptina/sangue , Obesidade/sangue , Fator de Crescimento Placentário/sangue , Efeitos Tardios da Exposição Pré-Natal/sangue , Adiposidade/genética , Animais , Pressão Sanguínea/genética , Peso Corporal/genética , Dieta Hiperlipídica , Modelos Animais de Doenças , Feminino , Humanos , Hipertensão/genética , Hipertensão/fisiopatologia , Masculino , Herança Materna/genética , Obesidade/genética , Obesidade/fisiopatologia , Gravidez , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Desmame
9.
Vasc Health Risk Manag ; 16: 249-256, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32612360

RESUMO

Background: The role of metabolic states in cardiovascular risks among individuals with varying degrees of obesity is unknown. The study aimed to compare cardiometabolic index (CMI), atherogenic index of plasma (AIP), lipid accumulation product (LAP) and novel anthropometric indices in metabolic and non-metabolically obese individual with regard to the role of FTO gene in Iranian adults. Methods: In total, 165 individuals were recruited into this cross-sectional study. Individuals grouped into four groups: metabolic healthy normal-weight (MHNW) individuals, metabolically unhealthy normal-weight (MUNW) individuals, metabolically healthy obese (MHO) individuals and metabolic unhealthy obese (MUO) individuals. The dietary intake was evaluated by food frequency questionnaire (FFQ). The cardiovascular indices (CMI, AIP and LAP) were calculated. A variety of anthropometric indices were calculated, including body adiposity Index (BAI), weight-adjusted-waist index (WWI), A body shape index (ABSI) and waist-height ratio (WHR). The genotypes of FTO-rs9939609 subjects were detected by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Results: The individuals with metabolically unhealthy phenotypes (MUO, MUNW) have higher levels of triglyceride and cardiovascular indices (AIP, LAP and CMI) than the individuals with metabolic healthy phenotypes (MHO, MHNW). With a similar degree of obesity, the anthropometric indices (BAI, WWI and WHR) levels were higher in metabolic unhealthy groups than metabolically healthy groups. The highest frequency of obesity-risk allele AA of FTO gene was observed in MUO, MHO, MUNW and MHNW, respectively. Conclusion: Normal-weight individuals with metabolic unhealthy status are at higher risk for cardiovascular diseases than obese individuals with metabolically healthy status. The genotype frequencies of obesity-risk allele AA of FTO gene were higher in obesity phenotypes than metabolic phenotypes.


Assuntos
Dioxigenase FTO Dependente de alfa-Cetoglutarato/genética , Doenças Cardiovasculares/genética , Metabolismo Energético/genética , Síndrome Metabólica/genética , Obesidade Metabolicamente Benigna/genética , Obesidade/genética , Polimorfismo de Nucleotídeo Único , Adulto , Idoso , Antropometria , Biomarcadores/sangue , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Estudos Transversais , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade Metabolicamente Benigna/sangue , Obesidade Metabolicamente Benigna/diagnóstico , Fenótipo , Medição de Risco , Fatores de Risco , Adulto Jovem
10.
Obesity (Silver Spring) ; 28(10): 1815-1825, 2020 10.
Artigo em Inglês | MEDLINE | ID: mdl-32602202

RESUMO

OBJECTIVE: This study aims to explore the indicators for severity of coronavirus disease 2019 (COVID-19) in young patients between the ages of 18 and 40 years. METHODS: This retrospective cohort study included 65 consecutively admitted patients with COVID-19 who were between 18 and 40 years old in Zhongnan Hospital of Wuhan University in Wuhan, China. Among them, 53 were moderate cases, and 12 were severe or critical cases. Epidemiological, clinical, and laboratory characteristics and treatment data were collected. A multivariate logistic regression analysis was implemented to explore risk factors. RESULTS: The patients with severe/critical cases had obviously higher BMI (average 29.23 vs. 22.79 kg/m2 ) and lower liver computed tomography value (average 50.00 vs. 65.00 mU) than the group of moderate cases. The patients with severe/critical cases had higher fasting glucose, alanine aminotransferase, aspartate aminotransferase, and creatinine compared with patients with moderate cases (all P < 0.01). More severe/critical cases (58.33% vs. 1.92%) had positive urine protein levels. The severe/critical cases also experienced a significant process of serum albumin decline. Logistic regression analysis showed that male sex, high BMI (especially obesity), elevated fasting blood glucose, and urinary protein positivity were all risk factors for young patients with severe COVID-19. CONCLUSIONS: Obesity is an important predictor of COVID-19 severity in young patients. The main mechanism is related to damage of the liver and kidney.


Assuntos
Fatores Etários , Betacoronavirus , Infecções por Coronavirus/sangue , Obesidade/sangue , Pneumonia Viral/sangue , Índice de Gravidade de Doença , Adolescente , Adulto , Idoso , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Glicemia/análise , Índice de Massa Corporal , China/epidemiologia , Infecções por Coronavirus/complicações , Infecções por Coronavirus/virologia , Creatinina/sangue , Feminino , Hospitalização/estatística & dados numéricos , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Obesidade/virologia , Pandemias , Pneumonia Viral/complicações , Pneumonia Viral/virologia , Estudos Retrospectivos , Fatores de Risco , Albumina Sérica/análise , Adulto Jovem
11.
PLoS One ; 15(7): e0236451, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32697789

RESUMO

BACKGROUND: Lifestyle habits associate with metabolic health in overall populations. Whether such association is similar among subjects with a different nutritional status has been less studied. We aimed to (i) determine the prevalence of metabolic phenotypes in Chile, and (ii) determine the association between lifestyle habits and metabolic health according to the nutritional status. METHODS: The National Health Survey of Chile 2016-2017 was analyzed. A metabolically unhealthy phenotype was defined as manifesting ≥3 of the following risk factors: elevated blood pressure, elevated triglycerides, elevated glucose, elevated waist circumference, or reduced high-density lipoprotein cholesterol. Individuals manifesting <2 risk factors were considered as healthy. The nutritional status was defined as normal weight (18.5 to <25 kg/m2), overweight (25 to <30 kg/m2) or obesity (≥30 kg/m2). Questionnaires were used to estimate smoking habits, alcohol intake, sedentary behavior, moderate-vigorous physical activity, fruits/vegetables consumption, and fish/seafood consumption. The association (odds ratio [95%CI]) between lifestyle habits and metabolic health was determined within each nutritional status, adjusting for age, sex, BMI (in kg/m2), and education. RESULTS: The prevalence of a metabolically unhealthy phenotype was 36% in the overall sample. Such a prevalence was 7%, 33% and 58% among subjects with normal weight, overweight and obesity, respectively. In subjects with normal weight, the highest quartile of fruits/vegetables consumption was associated with reduced odds of having a metabolically unhealthy phenotype (0.09 [0.01-0.48]). In subjects with obesity, the highest quartile of moderate-vigorous physical activity was associated with reduced odds of having a metabolically unhealthy phenotype (0.29 [0.09-0.91]). CONCLUSION: One third of the Chilean population manifests an unhealthy phenotype. We identified associations between lifestyle habits and metabolic health that are specific to the nutritional status. Thus, emphasizing fruits/vegetables consumption in subjects with normal weight, and physical activity in subjects with obesity, may maximize the benefits of public health interventions.


Assuntos
Hábitos , Estilo de Vida , Síndrome Metabólica/epidemiologia , Estado Nutricional/fisiologia , Adolescente , Adulto , Idoso , Glicemia/análise , Chile/epidemiologia , HDL-Colesterol/sangue , Estudos Transversais , Escolaridade , Feminino , Inquéritos Epidemiológicos/estatística & dados numéricos , Humanos , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/metabolismo , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/diagnóstico , Obesidade/epidemiologia , Obesidade/metabolismo , Sobrepeso/sangue , Sobrepeso/epidemiologia , Sobrepeso/metabolismo , Prevalência , Fatores de Risco , Circunferência da Cintura/fisiologia , Adulto Jovem
12.
Lancet Diabetes Endocrinol ; 8(9): 782-792, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32687793

RESUMO

Since the initial COVID-19 outbreak in China, much attention has focused on people with diabetes because of poor prognosis in those with the infection. Initial reports were mainly on people with type 2 diabetes, although recent surveys have shown that individuals with type 1 diabetes are also at risk of severe COVID-19. The reason for worse prognosis in people with diabetes is likely to be multifactorial, thus reflecting the syndromic nature of diabetes. Age, sex, ethnicity, comorbidities such as hypertension and cardiovascular disease, obesity, and a pro-inflammatory and pro-coagulative state all probably contribute to the risk of worse outcomes. Glucose-lowering agents and anti-viral treatments can modulate the risk, but limitations to their use and potential interactions with COVID-19 treatments should be carefully assessed. Finally, severe acute respiratory syndrome coronavirus 2 infection itself might represent a worsening factor for people with diabetes, as it can precipitate acute metabolic complications through direct negative effects on ß-cell function. These effects on ß-cell function might also cause diabetic ketoacidosis in individuals with diabetes, hyperglycaemia at hospital admission in individuals with unknown history of diabetes, and potentially new-onset diabetes.


Assuntos
Betacoronavirus , Infecções por Coronavirus/epidemiologia , Infecções por Coronavirus/terapia , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/terapia , Pneumonia Viral/epidemiologia , Pneumonia Viral/terapia , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/epidemiologia , Doenças Cardiovasculares/terapia , Infecções por Coronavirus/sangue , Diabetes Mellitus Tipo 2/sangue , Humanos , Hiperglicemia/sangue , Hiperglicemia/epidemiologia , Hiperglicemia/terapia , Hipertensão/sangue , Hipertensão/epidemiologia , Hipertensão/terapia , Obesidade/sangue , Obesidade/epidemiologia , Obesidade/terapia , Pandemias , Pneumonia Viral/sangue , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento
13.
Ecotoxicol Environ Saf ; 201: 110785, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32505049

RESUMO

Environmental pollutants may play a role in the aetiology of obesity beyond conventional factors. The associations between environmental exposure to aldehydes and obesity remain unclear. The objective of this study is to determine whether aldehyde exposure is associated with obesity in adults. We analysed data from 1977 participants in the National Health and Nutrition Examination Survey (NHANES) 2013-2014 aged ≥ 18 years. Obesity was assessed through body mass index (BMI) measurements. Generalized linear regression and restricted cubic spline models were analysed to assess the association between aldehydes and outcomes. After multivariable adjustment, isopentanaldehyde was inversely associated with obesity, while no significant association was observed between any other aldehydes and obesity. Compared with the lowest quartile, the adjusted odds ratio (OR) of obesity with a 95% confidence interval (CI) for the highest quartile was 0.50 (0.35, 0.70) for isopentanaldehyde. Analyses using a restricted cubic spline indicated that the association between isopentanaldehyde and obesity is nonlinear. Threshold effect analysis demonstrated that the inflection point of isopentanaldehyde was 1.26 ng/ml. Each 1-fold increase in isopentanaldehyde exhibited an 18% decrease in the odds of obesity (OR 0.82, 95% CI 0.79-1.09) on the left side of the inflection point and an 81% decrease (OR 0.19, 95% CI 0.08-0.45) on the right side of the inflection point. Similar associations were also observed among isopentanaldehyde and abdominal obesity, BMI, and waist circumference. These cross-sectional results show a nonlinear and inverse association between isopentanaldehyde and obesity.


Assuntos
Aldeídos/sangue , Exposição Ambiental/análise , Poluentes Ambientais/sangue , Obesidade/epidemiologia , Adulto , Idoso , Índice de Massa Corporal , Estudos Transversais , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Modelos Lineares , Masculino , Pessoa de Meia-Idade , Inquéritos Nutricionais , Obesidade/sangue , Obesidade/induzido quimicamente , Razão de Chances , Estados Unidos/epidemiologia , Circunferência da Cintura
14.
PLoS One ; 15(6): e0232749, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32574162

RESUMO

BACKGROUND: Maternal obesity is increasing worldwide but the consequences for maternal physiology and fetal growth are not fully understood. OBJECTIVE: To study whether changes in glucose and lipid metabolism during pregnancy differ between women with normal weight and overweight/obesity, and investigate which of these metabolic factors are associated with birthweight. DESIGN: Prospective, longitudinal study. SETTING: Department of Obstetrics, Oslo University Hospital, Rikshospitalet. POPULATION: 1031 healthy pregnant women with singleton pregnancies. METHODS: Blood samples from early and late pregnancy were analyzed for fasting glucose, insulin and lipids (total cholesterol, HDL-cholesterol, LDL-cholesterol and triglycerides). Associations between metabolic factors and birthweight (z-scores) were explored by linear regression models. Main Outcome Measures: Group-dependent longitudinal changes in glucose and lipids and their association with birthweight (z-scores). RESULTS: Compared to women with normal weight (BMI < 25), women with overweight (BMI 25-29.9) and obesity (BMI > 30) had significantly higher fasting glucose (4.54, 4.68 and 4.84 mmol/l), insulin (23, 33 and 50 pmol/l), total cholesterol (4.85, 4.99 and 5.14 mmol/l), LDL-C (2.49, 2.66 and 2.88 mmol/l) and triglycerides (1.10, 1.28 and 1.57 mmol/l), but lower HDL-C (1.86, 1.75 and 1.55 mmol/l). BMI (B 0.05, 95% CI 0.03-0.06, p<0.001), gestational weight gain (GWG) (B 0.06, 0.05-0.08, p<0.001) and an increase in fasting glucose (B 0.30, 0.16-0.43, p<0.001) were positively associated with birthweight, whereas a decrease in HDL-C (B -0.72, -0.96- -0.53, p<0.001) had a negative association with birthweight. CONCLUSIONS: Overweight/obesity was associated with an unfavorable metabolic profile in early pregnancy which was associated with increased birthweight. However, modifiable factors like gestational weight gain and an increase in fasting glucose were identified and can be targeted for interventions.


Assuntos
Peso ao Nascer , Glicemia , Índice de Massa Corporal , Lipídeos/sangue , Obesidade/epidemiologia , Complicações na Gravidez/epidemiologia , Adulto , Feminino , Ganho de Peso na Gestação , Humanos , Insulina/sangue , Estudos Longitudinais , Obesidade/sangue , Gravidez , Complicações na Gravidez/sangue , Estudos Prospectivos
15.
PLoS One ; 15(6): e0234319, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32542057

RESUMO

AIMS: Robust evidence supports intensive glucose control in those with recently diagnosed type 1 diabetes to reduce the risk of developing micro- and macrovascular complications. Data to support longitudinal glycaemic targets is lacking. We aimed to explore if longer duration of diabetes and greater age might reduce the impact of glycaemia on the risk of vascular complications. RESEARCH AND DESIGN METHODS: Data for adults age 20 years or more, was extracted from a clinical database of people with type 1 diabetes cared for at a London teaching hospital. The presence or absence of micro- and macro-vascular complications was recorded. Multivariable logistic regression analysis was performed using HbA1c as independent variable, diabetes duration and age as continuous variable and obesity, hypertension, hypercholesterolaemia, low HDL cholesterol and hypertriglyceridaemia as categorical variables. RESULTS: Data from 495 patients was used. HbA1c above 60 mmol/mol (7.6%) was associated with increased microvascular complications in patients aged 20-44 years, independent of age and duration of diabetes. In older people with T1DM duration of diabetes was the major risk factor. CONCLUSIONS: Our study suggests that increased age and greater duration of diabetes reduce the impact of glycaemia on the risk of vascular complications. Intensive blood glucose management in patients aged ≥45 years may have limited benefits in terms of reducing the risk of complications although this does not dismiss the benefits of good glycaemic control in older people with T1DM.


Assuntos
Diabetes Mellitus Tipo 1/sangue , Angiopatias Diabéticas/sangue , Hemoglobina A Glicada/metabolismo , Adulto , Idoso , Idoso de 80 Anos ou mais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Angiopatias Diabéticas/prevenção & controle , Feminino , Carga Glicêmica , Humanos , Hipoglicemiantes , Insulina/sangue , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Fatores de Risco , Adulto Jovem
16.
Life Sci ; 256: 117962, 2020 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-32534040

RESUMO

AIMS: The aim of the present study was to evaluate the oral resveratrol effects associated with diet and physical training changes on anthropometric and biochemical parameters. MAIN METHODS: 25 individuals aged from 30 to 60 years old; with Body Mass Index (BMI) ≥ 30 kg/m2 were included in the study. Following the primary evaluation (anthropometric and clinical), the patients were randomly divided into 2 groups: (1) Placebo: Physical activity program + Diet + Placebo; (2) Resveratrol: Physical activity program + Diet + Resveratrol (RVS) (250 mg/day) for three months. Anthropometric and biochemical parameters were evaluated at baseline and after the treatment period. KEY FINDINGS: The main findings showed that the resveratrol supplementation improved total cholesterol (TC), High-density Lipoprotein cholesterol (HDL-c), Very-low density Lipoprotein cholesterol (VLDL-c), urea, creatinine and albumin serum levels. SIGNIFICANCE: These findings indicate that this polyphenol may be an option to potentiate the beneficial effects induced by dietary and physical activity programs in the Metabolic Syndrome (MetS) treatment.


Assuntos
Suplementos Nutricionais , Estilo de Vida , Síndrome Metabólica/complicações , Síndrome Metabólica/tratamento farmacológico , Obesidade/complicações , Resveratrol/administração & dosagem , Resveratrol/uso terapêutico , Administração Oral , Adulto , Metabolismo Energético/efeitos dos fármacos , Feminino , Humanos , Lipídeos/sangue , Masculino , Síndrome Metabólica/sangue , Pessoa de Meia-Idade , Obesidade/sangue , Placebos
17.
Nat Commun ; 11(1): 2995, 2020 06 12.
Artigo em Inglês | MEDLINE | ID: mdl-32532984

RESUMO

Adipocyte dysfunction links obesity to insulin resistance and type 2 diabetes. Adipocyte function is regulated by receptor-mediated activation of heterotrimeric G proteins. Little is known about the potential in vivo metabolic roles of Gi-type G proteins expressed by adipocytes, primarily due to the lack of suitable animal models. To address this question, we generated mice lacking functional Gi proteins selectively in adipocytes. Here we report that these mutant mice displayed significantly impaired glucose tolerance and reduced insulin sensitivity when maintained on an obesogenic diet. In contrast, using a chemogenetic strategy, we demonstrated that activation of Gi signaling selectively in adipocytes greatly improved glucose homeostasis and insulin signaling. We also elucidated the cellular mechanisms underlying the observed metabolic phenotypes. Our data support the concept that adipocyte Gi signaling is essential for maintaining euglycemia. Drug-mediated activation of adipocyte Gi signaling may prove beneficial for restoring proper glucose homeostasis in type 2 diabetes.


Assuntos
Adipócitos/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/genética , Resistência à Insulina/genética , Transdução de Sinais/genética , Adipócitos/citologia , Animais , Glicemia/metabolismo , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/metabolismo , Subunidades alfa Gi-Go de Proteínas de Ligação ao GTP/metabolismo , Perfilação da Expressão Gênica/métodos , Intolerância à Glucose/genética , Homeostase/genética , Insulina/sangue , Insulina/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Transgênicos , Obesidade/sangue , Obesidade/genética , Obesidade/metabolismo
18.
Maturitas ; 137: 50-56, 2020 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32498937

RESUMO

OBJECTIVES: To understand the extent to which risk factors for insulin resistance are mediated by body mass index (BMI), visceral adipose tissue (VAT), physical activity and performance, and the inflammatory markers interleukin (IL)-6, tumor necrosis factor (TNF)- α, and high-sensitivity C-reactive protein (hs-CRP). STUDY DESIGN: A wide range of socio-demographic characteristics of Chinese, Malay and Indian women attending routine gynecologic care in Singapore were prospectively collected. Physical performance was objectively measured by hand grip strength and the Short Physical Performance Battery. Percent VAT was determined by dual-energy X-ray absorptiometry. Fasting serum concentrations of glucose, insulin, IL-6, TNF- α, and hs-CRP were measured. MAIN OUTCOME MEASURE: was insulin resistance, expressed as the homeostatic model assessment of insulin resistance (HOMA-IR). RESULTS: 1159 women were analyzed, mean age 56.3 (range 45-69) years, comprising women of Chinese (84.0%), Indian (10.2%), and Malay (5.7%) ethnic origins. The adjusted mean differences for obesity (0.66, 95% CI 0.32-1.00), VAT area in the highest vs lowest tertile (1.03, 95% CI 0.73-1.34), low physical performance (0.63, 95% CI 0.05-1.24), and highest vs lowest tertile of TNF- α (0.35, 95% CI 0.13-0.57) were independently associated with HOMA-IR. Women of Malay and Indian ethnicity had higher crude HOMA-IR than Chinese women. However, after adjustment for obesity, VAT, physical performance, and TNF- α, no differences in mean HOMA-IR remained, when comparing Chinese women with those of Malay ethnicity (0.27, 95% CI -0.12 to 0.66) and with those of Indian ethnicity (0.30, 95% CI -0.01 to 0.66). CONCLUSIONS: Insulin resistance was independently associated with obesity, high VAT, low physical performance, and high levels of TNF- α in midlife Singaporean women. These variables entirely explained the significant differences in insulin resistance between women of Chinese, Malay and Indian ethnicity.


Assuntos
Resistência à Insulina/etnologia , Interleucina-6/sangue , Gordura Intra-Abdominal , Obesidade/fisiopatologia , Fator de Necrose Tumoral alfa/sangue , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Índice de Massa Corporal , Proteína C-Reativa/metabolismo , China/etnologia , Exercício Físico , Feminino , Força da Mão , Humanos , Índia/etnologia , Insulina , Malásia/etnologia , Pessoa de Meia-Idade , Obesidade/sangue , Desempenho Físico Funcional , Fatores de Risco , Singapura
20.
PLoS One ; 15(6): e0234970, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32589682

RESUMO

The incidence of type 2 diabetes is increasing more rapidly in adolescents than in any other age group. We identified and compared metabolite signatures in obese children with type 2 diabetes (T2D), obese children without diabetes (OB), and healthy, age- and gender-matched normal weight controls (NW) by measuring 273 analytes in fasting plasma and 24-hour urine samples from 90 subjects by targeted LC-MS/MS. Diabetic subjects were within 2 years of diagnosis in an attempt to capture early-stage disease prior to declining renal function. We found 22 urine metabolites that were uniquely associated with T2D when compared to OB and NW groups. The metabolites most significantly elevated in T2D youth included members of the betaine pathway, nucleic acid metabolism, and branched-chain amino acids (BCAAs) and their catabolites. Notably, the metabolite pattern in OB and T2D groups differed between urine and plasma, suggesting that urinary BCAAs and their intermediates behaved as a more specific biomarker for T2D, while plasma BCAAs associated with the obese, insulin resistant state independent of diabetes status. Correlative analysis of metabolites in the T2D signature indicated that betaine metabolites, BCAAs, and aromatic amino acids were associated with hyperglycemia, but BCAA acylglycine derivatives and nucleic acid metabolites were linked to insulin resistance. Of major interest, we found that urine levels of succinylaminoimidazole carboxamide riboside (SAICA-riboside) were increased in diabetic youth, identifying urine SAICA-riboside as a potential biomarker for T2D.


Assuntos
Diabetes Mellitus Tipo 2/metabolismo , Resistência à Insulina , Obesidade/metabolismo , Purinas/biossíntese , Adolescente , Aminoácidos de Cadeia Ramificada/metabolismo , Betaína/metabolismo , Biomarcadores/sangue , Biomarcadores/metabolismo , Biomarcadores/urina , Vias Biossintéticas , Cromatografia Líquida de Alta Pressão , Biologia Computacional , Estudos Transversais , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/urina , Feminino , Humanos , Masculino , Metabolômica/métodos , Ácidos Nucleicos/metabolismo , Obesidade/sangue , Obesidade/urina , Espectrometria de Massas em Tandem , Adulto Jovem
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