Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 5.068
Filtrar
1.
Hautarzt ; 71(10): 762-771, 2020 Oct.
Artigo em Alemão | MEDLINE | ID: mdl-32886132

RESUMO

Hidradenitis suppurativa (HS) is a chronic, recurrent cutaneous disease of the terminal hair follicle which manifests with deep-seated, painful nodules, abscesses, and sinus tract formation. The pathophysiology of the disease includes among various factors also dermatoendocrinologic variables: Correlations with metabolic syndrome, obesity, sex steroid hormones, and the improvement after antiandrogen therapy are some of the key points presented in this review. Hormonal treatment of HS can be an effective and inexpensive alternative or add-on therapy to classic HS treatments, especially in cases where antibiotics and/or biologics are ineffective or contraindicated.


Assuntos
Abscesso/etiologia , Doenças do Sistema Endócrino/metabolismo , Hormônios Esteroides Gonadais/metabolismo , Hidradenite Supurativa/fisiopatologia , Síndrome Metabólica/metabolismo , Antagonistas de Androgênios/uso terapêutico , Diabetes Mellitus/metabolismo , Dislipidemias/metabolismo , Folículo Piloso , Hidradenite Supurativa/tratamento farmacológico , Hidradenite Supurativa/metabolismo , Hormônios/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Obesidade/metabolismo
2.
PLoS One ; 15(8): e0238388, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32866186

RESUMO

BACKGROUND: The prevalence of nonalcoholic fatty liver disease (NAFLD) in the non-obese population has increased and NAFLD is not always recognized in individuals with metabolic syndrome (MS). The risk of cirrhosis is higher in patients having NAFLD with elevated alanine aminotransferase (ALT) levels than in those having NAFLD with normal ALT levels. OBJECTIVE: To measure the differences in clinical factors associated with NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and to measure differences in metabolites between MS subjects with and without NAFLD having elevation of ALT. METHODS: Among 7,054 persons undergoing health check-ups, we included 3,025 subjects who met the selection criteria. We measured differences in clinical factors for NAFLD having elevation of ALT among subjects with Non-MS, Pre-MS, and MS, and compared metabolites between subjects with and without NAFLD having elevation of ALT in 32 subjects with MS. RESULTS: The prevalence of NAFLD and NAFLD having elevation of ALT was significantly progressively greater in subjects with Non-MS, Pre-MS, and MS (p <0.001, respectively). In the Non-MS group, there were significant differences between subjects with and without NAFLD having elevation of ALT with respect to body mass index (BMI), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol, hemoglobin A1c, uric acid, aspartate aminotransferase (AST); In the Pre-MS group, there were significant differences in BMI, hypertension, AST, and gamma-glutamyl transpeptidase (GGT); In the MS group, there were significant differences in HDL-C, impaired glucose tolerance, AST, and GGT. There were significant differences in levels of metabolites of nicotinamide, inosine, and acetyl-L-carnitine between MS subjects with and without NAFLD having elevation of ALT (all p <0.05). CONCLUSIONS: Although NAFLD having elevation of ALT is important for development of NAFLD, differences in factors associated with NAFLD having elevation of ALT at various stages of MS should be considered. Additionally, several metabolites may play roles in the identification of risk for NAFLD in individuals with MS.


Assuntos
Alanina Transaminase/metabolismo , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/metabolismo , Aspartato Aminotransferases/metabolismo , Índice de Massa Corporal , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Hemoglobina A Glicada/metabolismo , Humanos , Fígado/metabolismo , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Ácido Úrico/metabolismo , gama-Glutamiltransferase/metabolismo
3.
PLoS One ; 15(8): e0231234, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32804947

RESUMO

Cardiometabolic syndrome has become a global health issue. Heart failure is a common comorbidity of cardiometabolic syndrome. Successful drug development to prevent cardiometabolic syndrome and associated comorbidities requires preclinical models predictive of human conditions. To characterize the heart failure component of cardiometabolic syndrome, cardiometabolic, metabolic, and renal biomarkers were evaluated in lean and obese ZSF1 19- to 32-week-old male rats. Histopathological assessment of kidneys and hearts was performed. Cardiac function, exercise capacity, and left ventricular gene expression were also analyzed. Obese ZSF1 rats exhibited multiple features of human cardiometabolic syndrome by pathological changes in systemic renal, metabolic, and cardiovascular disease circulating biomarkers. Hemodynamic assessment, echocardiography, and decreased exercise capacity confirmed heart failure with preserved ejection fraction. RNA-seq results demonstrated changes in left ventricular gene expression associated with fatty acid and branched chain amino acid metabolism, cardiomyopathy, cardiac hypertrophy, and heart failure. Twelve weeks of growth differentiation factor 15 (GDF15) treatment significantly decreased body weight, food intake, blood glucose, and triglycerides and improved exercise capacity in obese ZSF1 males. Systemic cardiovascular injury markers were significantly lower in GDF15-treated obese ZSF1 rats. Obese ZSF1 male rats represent a preclinical model for human cardiometabolic syndrome with established heart failure with preserved ejection fraction. GDF15 treatment mediated dietary response and demonstrated a cardioprotective effect in obese ZSF1 rats.


Assuntos
Fator 15 de Diferenciação de Crescimento/metabolismo , Fator 15 de Diferenciação de Crescimento/farmacologia , Síndrome Metabólica/metabolismo , Animais , Biomarcadores/metabolismo , Coração/fisiologia , Insuficiência Cardíaca/fisiopatologia , Ventrículos do Coração/fisiopatologia , Rim/metabolismo , Masculino , Síndrome Metabólica/complicações , Miocárdio/metabolismo , Obesidade/complicações , Ratos , Ratos Endogâmicos , Ratos Zucker , Volume Sistólico/fisiologia , Função Ventricular Esquerda/efeitos dos fármacos , Função Ventricular Esquerda/fisiologia
4.
Nat Commun ; 11(1): 3412, 2020 07 08.
Artigo em Inglês | MEDLINE | ID: mdl-32641742

RESUMO

Regulatory B cells restrict immune and inflammatory responses across a number of contexts. This capacity is mediated primarily through the production of IL-10. Here we demonstrate that the induction of a regulatory program in human B cells is dependent on a metabolic priming event driven by cholesterol metabolism. Synthesis of the metabolic intermediate geranylgeranyl pyrophosphate (GGPP) is required to specifically drive IL-10 production, and to attenuate Th1 responses. Furthermore, GGPP-dependent protein modifications control signaling through PI3Kδ-AKT-GSK3, which in turn promote BLIMP1-dependent IL-10 production. Inherited gene mutations in cholesterol metabolism result in a severe autoinflammatory syndrome termed mevalonate kinase deficiency (MKD). Consistent with our findings, B cells from MKD patients induce poor IL-10 responses and are functionally impaired. Moreover, metabolic supplementation with GGPP is able to reverse this defect. Collectively, our data define cholesterol metabolism as an integral metabolic pathway for the optimal functioning of human IL-10 producing regulatory B cells.


Assuntos
Linfócitos B Reguladores/metabolismo , Colesterol/metabolismo , Interleucina-10/metabolismo , Fosfatos de Poli-Isoprenil/metabolismo , Animais , Antígenos CD19/metabolismo , Classe I de Fosfatidilinositol 3-Quinases/metabolismo , Técnicas de Cocultura , Doenças Hereditárias Autoinflamatórias/metabolismo , Humanos , Macrófagos/metabolismo , Síndrome Metabólica/metabolismo , Deficiência de Mevalonato Quinase/metabolismo , Camundongos , Fosfatidilinositol 3-Quinases/metabolismo , Fator 1 de Ligação ao Domínio I Regulador Positivo/metabolismo , Análise de Componente Principal , Transdução de Sinais , Células Th1/metabolismo , Receptor Toll-Like 9/metabolismo , Fator de Necrose Tumoral alfa/metabolismo
5.
J Virol ; 94(18)2020 08 31.
Artigo em Inglês | MEDLINE | ID: mdl-32661141

RESUMO

Metabolic syndrome increases the risk of severe disease due to viral infection. Yet few studies have assessed the pathogenesis of respiratory viruses in high-risk populations. Here, we summarize how metabolic dysregulation impairs immune responses, and we define the role of metabolism during influenza virus and coronavirus infections. We also discuss the use of various in vitro, in vivo, and ex vivo models to elucidate the contributions of host factors to viral susceptibility, immunity, and disease severity.


Assuntos
Infecções por Coronavirus/complicações , Suscetibilidade a Doenças , Influenza Humana/complicações , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Animais , Biomarcadores , Infecções por Coronavirus/virologia , Modelos Animais de Doenças , Humanos , Influenza Humana/virologia , Síndrome Metabólica/diagnóstico
6.
Endocrinology ; 161(10)2020 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-32603424

RESUMO

The ongoing coronavirus disease 2019 (COVID-19) pandemic is caused by the novel coronavirus, severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). Individuals with metabolic syndrome are at increased risk for poor disease outcomes and mortality from COVID-19. The pathophysiologic mechanisms for these observations have not been fully elucidated. A critical interaction between SARS-CoV-2 and the angiotensin-converting enzyme 2 (ACE2) facilitates viral entry into the host cell. ACE2 is expressed in pancreatic islets, vascular endothelium, and adipose tissue, and the SARS-CoV-2 -ACE2 interaction in these tissues, along with other factors, governs the spectrum and the severity of clinical manifestations among COVID-19 patients with metabolic syndrome. Moreover, the pro-inflammatory milieu observed in patients with metabolic syndrome may contribute toward COVID-19-mediated host immune dysregulation, including suboptimal immune responses, hyperinflammation, microvascular dysfunction, and thrombosis. This review describes the spectrum of clinical features, the likely pathophysiologic mechanisms, and potential implications for the management of metabolic syndrome in COVID-19 patients.


Assuntos
Infecções por Coronavirus/fisiopatologia , Síndrome Metabólica/fisiopatologia , Pneumonia Viral/fisiopatologia , Animais , Betacoronavirus/fisiologia , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Infecções por Coronavirus/virologia , Sistema Endócrino/metabolismo , Sistema Endócrino/fisiopatologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/fisiopatologia , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Microvasos/fisiopatologia , Pandemias , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/imunologia , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo , Pneumonia Viral/virologia
7.
Life Sci ; 257: 118032, 2020 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-32621920

RESUMO

Diabetes mellitus is one of the major global health issues, which is closely related to metabolic dysfunction and the chronic inflammatory diseases. Multiple studies have demonstrated that serum bilirubin is negatively correlated with metabolic syndrome and associated inflammatory diseases, including atherosclerosis, hypertension, etc. However, the roles of bilirubin in metabolic syndrome and associated inflammatory diseases still remain unclear. Here, we explain the role of bilirubin in metabolic syndrome and chronic inflammatory diseases and its therapeutic potential. Understanding the role of bilirubin activities in diabetes may serve as a therapeutic target for the treatment of chronic inflammatory diseases in diabetic patients.


Assuntos
Bilirrubina/metabolismo , Bilirrubina/fisiologia , Síndrome Metabólica/metabolismo , Aterosclerose/sangue , Bilirrubina/sangue , Humanos , Hipertensão/sangue , Síndrome Metabólica/sangue , Síndrome Metabólica/imunologia
8.
PLoS One ; 15(7): e0236357, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32687509

RESUMO

Adult growth hormone deficiency (GHD) is being increasingly recognized to cause premature mortality exacerbated by oxidative stress. A case-control observational study has been performed with the primary objective of evaluating new parameters of oxidative stress and macromolecular damage in adult GHD subjects: serum nitrotryptophan; Total Antioxidant Capacity expressed as LAG time; urinary hexanoil-lysine; urinary dityrosine and urinary 8-OH-deoxyguanosine. GHD was diagnosed using Growth Hormone-Releasing Hormone 50µg iv+arginine 0,5 g/Kg test, with a peak GH response <9 µg /L when BMI was <30 kg/m2 or <4 µg/L when BMI was >30 kg/m2. Patients affected by adult GHD were divided into three groups, total GHD (n = 26), partial GHD (n = 25), and controls (n = 29). Total Antioxidant Capacity, metabolic and hormonal parameters have been determined in separate plasma samples; nitrotryptophan in serum samples; hexanoil-lysine, dityrosine, 8-OH-deoxyguanosine in urine samples. Assessment of hexanoil-lysine exhibited a trend to increase in comparing total GHD vs partial and controls, although not significant. Values of 8-OH-deoxyguanosine did not significantly differ among the three groups. Significant lower levels of dityrosine in partial GHD vs total and controls were found. No significant difference in nitrotriptophan serum levels was found, while significantly greater values of Total Antioxidant Capacity were showed in total and partial GHD vs controls. Thus, our result confirm that oxidative stress is increased both in partial and total adult GHD. The lack of compensation by antioxidants in total GHD may be connected to the complications associated to this rare disorder.


Assuntos
Antioxidantes/análise , Hormônio do Crescimento Humano/deficiência , Hipopituitarismo/metabolismo , Síndrome Metabólica/metabolismo , Estresse Oxidativo/fisiologia , 8-Hidroxi-2'-Desoxiguanosina/urina , Adulto , Malformação de Arnold-Chiari/sangue , Malformação de Arnold-Chiari/complicações , Malformação de Arnold-Chiari/metabolismo , Biomarcadores/sangue , Biomarcadores/urina , Estudos de Casos e Controles , Síndrome da Sela Vazia/sangue , Síndrome da Sela Vazia/complicações , Síndrome da Sela Vazia/metabolismo , Feminino , Humanos , Hipopituitarismo/sangue , Hipopituitarismo/etiologia , Hipopituitarismo/urina , Peroxidação de Lipídeos , Lisina/sangue , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/etiologia , Síndrome Metabólica/urina , Pessoa de Meia-Idade , Triptofano/análogos & derivados , Triptofano/sangue , Tirosina/análogos & derivados , Tirosina/urina
9.
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
10.
Am J Physiol Heart Circ Physiol ; 319(2): H481-H487, 2020 08 01.
Artigo em Inglês | MEDLINE | ID: mdl-32678706

RESUMO

Modifiable cardiometabolic risk factors induce the release of proinflammatory cytokines and reactive oxygen species from circulating peripheral blood mononuclear cells (PBMCs), resulting in increased cardiovascular disease risk and compromised immune health. These changes may be driven by metabolic reprogramming of PBMCs, resulting in reduced mitochondrial respiration; however, this has not been fully tested. We aimed to determine the independent associations between cardiometabolic risk factors including BMI, blood pressure, fasting glucose, and plasma lipids with mitochondrial respiration in PBMCs isolated from generally healthy individuals (n = 21) across the adult lifespan (12 men/9 women; age, 56 ± 21 yr; age range, 22-78 yr; body mass index, 27.9 ± 5.7 kg/m2; blood pressure, 123 ± 16/72 ± 10 mmHg; glucose, 90 ± 14 mg/dL; low-density lipoprotein cholesterol (LDL-C), 111 ± 22 mg/dL; and high-density lipoprotein cholesterol (HDL-C), 62 ± 16 mg/dL). PBMCs were isolated from whole blood by density-dependent centrifugation and used to assess mitochondrial function by respirometry. Primary outcomes included basal and maximal oxygen consumption rate (OCR), which were subsequently used to determine spare respiratory capacity and OCR metabolic potential. After we corrected for systolic blood pressure (SBP), diastolic blood pressure (DBP), and blood glucose, LDL-C was negatively associated with maximal respiration (r = -0.56, P = 0.016), spare respiratory capacity (r = -0.58, P = 0.012), and OCR metabolic potential (r = -0.71, P = 0.0011). In addition, SBP was negatively associated with OCR metabolic potential (r = -0.62, P = 0.0056) after we corrected for DBP, blood glucose, and LDL-C. These data suggest a link between blood cholesterol, SBP, and mitochondrial health that may provide insight into how cardiometabolic risk factors contribute to impaired immune cell function.NEW & NOTEWORTHY Independent of other cardiometabolic risk factors, low-density lipoprotein cholesterol, and systolic blood pressure were found to be negatively associated with several parameters of mitochondrial respiration in peripheral blood mononuclear cells of healthy adults. These data suggest that low-density lipoprotein cholesterol and systolic blood pressure may induce metabolic reprogramming of immune cells, contributing to increased cardiovascular disease risk and impaired immune health.


Assuntos
Pressão Sanguínea , Respiração Celular , LDL-Colesterol/sangue , Leucócitos Mononucleares/metabolismo , Síndrome Metabólica/metabolismo , Mitocôndrias/metabolismo , Adulto , Idoso , Biomarcadores/sangue , Glicemia/análise , Índice de Massa Corporal , Jejum/sangue , Feminino , Humanos , Leucócitos Mononucleares/imunologia , Masculino , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/imunologia , Síndrome Metabólica/fisiopatologia , Pessoa de Meia-Idade , Mitocôndrias/imunologia , Consumo de Oxigênio , Fatores de Risco , Adulto Jovem
11.
PLoS One ; 15(6): e0234516, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32559253

RESUMO

The prevalence of metabolic syndrome is increased worldwide. Tobacco smoking increases the risk of developing metabolic syndrome. Waterpipe tobacco smoking has become a global trend of tobacco consumption and is as common as cigarette smoking. In this study, the effect of waterpipe tobacco smoke (WTS) on the development of metabolic syndrome in rats was evaluated. Adult Wistar rats were exposed for 19 weeks to either fresh air (control) or WTS for 1 hour daily/ 5 days per week (WTS). Central obesity, systolic blood pressure, lipid profile, glucose hemostasis and levels of leptin and adiponectin were evaluated. The WTS exposure increased body weight, abdominal circumference, systolic blood pressure and fasting glucose compared to control animals (P<0.05), consistent with inducing metabolic syndrome. The retroperitoneal fat, lipid profile and levels of insulin, leptin and adiponectin were not affected by WTS exposure (P>0.05). In conclusion, exposure to WTS has detrimental health effects leading to the development of metabolic syndrome in experimental animals.


Assuntos
Síndrome Metabólica/metabolismo , Efeitos Tardios da Exposição Pré-Natal/metabolismo , Fumar Tabaco/efeitos adversos , Tabaco para Cachimbos de Água/efeitos adversos , Animais , Modelos Animais de Doenças , Feminino , Humanos , Síndrome Metabólica/induzido quimicamente , Síndrome Metabólica/fisiopatologia , Estresse Oxidativo/efeitos dos fármacos , Gravidez , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Efeitos Tardios da Exposição Pré-Natal/fisiopatologia , Ratos , Cachimbos de Água
12.
Ann Biol Clin (Paris) ; 78(3): 243-252, 2020 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-32540813

RESUMO

Adiponectin is a major adipokine involved in energy homeostasis that exerts insulin-sensitizing properties. The level of adiponectin is reduced in situations of insulin resistance and is negatively associated with several pathophysiological situations including abdominal obesity, metabolic syndrome, steatosis and non-alcoholic steatohepatitis, type 2 diabetes, some cancers and cognitive diseases. These aspects are discussed in this review.


Assuntos
Adiponectina/fisiologia , Animais , Transtornos Cognitivos/etiologia , Transtornos Cognitivos/metabolismo , Transtornos Cognitivos/patologia , Diabetes Mellitus Tipo 2/etiologia , Diabetes Mellitus Tipo 2/metabolismo , Diabetes Mellitus Tipo 2/patologia , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina/fisiologia , Síndrome Metabólica/etiologia , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Neoplasias/etiologia , Neoplasias/metabolismo , Neoplasias/patologia , Obesidade/metabolismo , Obesidade/patologia , Obesidade/fisiopatologia
13.
Eur J Clin Invest ; 50(10): e13338, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32589264

RESUMO

BACKGROUND: Initial evidence from China suggests that most vulnerable subjects to COVID-19 infection suffer from pre-existing illness, including metabolic abnormalities. The pandemic characteristics and high-lethality rate of COVID-19 infection have raised concerns about interactions between virus pathobiology and components of the metabolic syndrome. METHODS: We harmonized the information from the recent existing literature on COVID-19 acute pandemic and mechanisms of damage in non-alcoholic fatty liver disease (NAFLD), as an example of chronic (non-communicable) metabolic pandemic. RESULTS: COVID-19-infected patients are more fragile with underlying metabolic illness, including hypertension, cardiovascular disease, type 2 diabetes, chronic lung diseases (e.g. asthma, chronic obstructive pulmonary disease and emphysema) and metabolic syndrome. During metabolic abnormalities, expansion of metabolically active fat ('overfat condition') parallels chronic inflammatory changes, development of insulin resistance and accumulation of fat in configuring NAFLD. The deleterious interplay of inflammatory pathways chronically active in NAFLD and acutely in COVID-19-infected patients, can explain liver damage in a subgroup of patients and might condition a worse outcome in metabolically compromised NAFLD patients. In a subgroup of patients with NAFLD, the underlying liver fibrosis might represent an additional and independent risk factor for severe COVID-19 illness, irrespective of metabolic comorbidities. CONCLUSIONS: NAFLD can play a role in the outcome of COVID-19 illness due to frequent association with comorbidities. Initial evidences suggest that increased liver fibrosis in NAFLD might affect COVID-19 outcome. In addition, long-term monitoring of post-COVID-19 NAFLD patients is advisable, to document further deterioration of liver damage. Further studies are required in this field.


Assuntos
Infecções por Coronavirus/epidemiologia , Síndrome Metabólica/epidemiologia , Hepatopatia Gordurosa não Alcoólica/epidemiologia , Pneumonia Viral/epidemiologia , Betacoronavirus , Infecções por Coronavirus/imunologia , Infecções por Coronavirus/metabolismo , Síndrome da Liberação de Citocina/imunologia , Humanos , Inflamação/imunologia , Resistência à Insulina , Fígado/imunologia , Fígado/metabolismo , Síndrome Metabólica/imunologia , Síndrome Metabólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Pandemias , Pneumonia Viral/imunologia , Pneumonia Viral/metabolismo
14.
PLoS One ; 15(5): e0227720, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32407314

RESUMO

Numerous mutational studies have demonstrated that circadian clock proteins regulate behavior and metabolism. Nr1d1(Rev-erbα) is a key regulator of circadian gene expression and a pleiotropic regulator of skeletal muscle homeostasis and lipid metabolism. Loss of Rev-erbα expression induces muscular atrophy, high adiposity, and metabolic syndrome in mice. Here we show that, unlike knockout mice, Nr1d1 heterozygous mice are not susceptible to muscular atrophy and in fact paradoxically possess larger myofiber diameters and improved neuromuscular function, compared to wildtype mice. Heterozygous mice lacked dyslipidemia, a characteristic of Nr1d1 knockout mice and displayed increased whole-body fatty-acid oxidation during periods of inactivity (light cycle). Heterozygous mice also exhibited higher rates of glucose uptake when fasted, and had elevated basal rates of gluconeogenesis compared to wildtype and knockout littermates. Rev-erbα ablation suppressed glycolysis and fatty acid-oxidation in white-adipose tissue (WAT), whereas partial Rev-erbα loss, curiously stimulated these processes. Our investigations revealed that Rev-erbα dose-dependently regulates glucose metabolism and fatty acid oxidation in WAT and muscle.


Assuntos
Dislipidemias/genética , Músculo Esquelético/metabolismo , Atrofia Muscular/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Tecido Adiposo Branco/metabolismo , Adiposidade/genética , Animais , Comportamento Animal/fisiologia , Relógios Circadianos/genética , Dislipidemias/metabolismo , Dislipidemias/patologia , Ácidos Graxos/metabolismo , Gluconeogênese/genética , Glucose/metabolismo , Heterozigoto , Humanos , Metabolismo dos Lipídeos/genética , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Síndrome Metabólica/patologia , Camundongos , Camundongos Knockout , Atrofia Muscular/metabolismo , Atrofia Muscular/patologia , Miofibrilas/genética , Miofibrilas/metabolismo , Miofibrilas/patologia , Fotoperíodo
15.
Ann Biol Clin (Paris) ; 78(3): 265-268, 2020 06 01.
Artigo em Inglês | MEDLINE | ID: mdl-32420886

RESUMO

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


Assuntos
Adiponectina/sangue , Biomarcadores/sangue , Doenças Cardiovasculares/etiologia , Técnicas de Diagnóstico Endócrino , Resistência à Insulina , Leptina/sangue , Adiponectina/análise , Biomarcadores/análise , Doenças Cardiovasculares/sangue , Doenças Cardiovasculares/diagnóstico , Diabetes Mellitus Tipo 2/complicações , Diabetes Mellitus Tipo 2/diagnóstico , Diabetes Mellitus Tipo 2/metabolismo , Humanos , Leptina/análise , Síndrome Metabólica/complicações , Síndrome Metabólica/diagnóstico , Síndrome Metabólica/metabolismo , Obesidade/complicações , Obesidade/diagnóstico , Obesidade/metabolismo , Prognóstico , Fatores de Risco
16.
Chemosphere ; 255: 127000, 2020 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-32417515

RESUMO

BACKGROUND: Bisphenol-A (BPA) exposure is widespread and early life exposure is associated with metabolic syndrome. While visceral adipose tissue (VAT) and subcutaneous adipose tissue (SAT) are implicated in the development of metabolic syndrome, the adipose depot-specific effects of prenatal BPA treatment are poorly understood. OBJECTIVE: To determine the impact of prenatal BPA exposure on genome-wide gene expression of VAT and SAT depots. METHODS: RNA sequencing was performed on SAT and VAT from 21-month old control and prenatal BPA-treated female sheep. Gene expression and pathway differences between SAT and VAT depots with or without prenatal BPA-treatment and the effect of prenatal BPA treatment on each depot were tested. RESULTS: There were 179 differentially expressed genes (padjusted < 0.05, log2-fold change >2.5) between SAT and VAT. Development and immune response pathways were upregulated in SAT, while metabolic pathways were upregulated in VAT. These adipose depot-specific genes and pathways were consistent with prenatal BPA-treatment. In SAT, BPA-treatment resulted in differential expression of 108 genes (78% upregulated with BPA) and altered pathways (immune response downregulated, RNA processing upregulated). In contrast in VAT, BPA-treatment differentially expressed 4 genes and upregulated chromatin and RNA processing pathways. CONCLUSION: Prenatal BPA-treatment induces adult depot-specific alterations in RNA expression in inflammation, RNA processing, and chromatin pathways, reflecting the diverse roles of SAT and VAT in regulating lipid storage and insulin sensitivity. These adipose tissue transcriptional dysregulations may contribute to the metabolic disorders observed in prenatal BPA-treated female sheep.


Assuntos
Adiposidade/efeitos dos fármacos , Compostos Benzidrílicos/toxicidade , Disruptores Endócrinos/toxicidade , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Gordura Intra-Abdominal/efeitos dos fármacos , Fenóis/toxicidade , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente , Gordura Subcutânea/efeitos dos fármacos , Adiposidade/genética , Animais , Compostos Benzidrílicos/sangue , Regulação para Baixo , Disruptores Endócrinos/sangue , Feminino , Perfilação da Expressão Gênica , Inflamação , Gordura Intra-Abdominal/crescimento & desenvolvimento , Gordura Intra-Abdominal/metabolismo , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo , Obesidade/metabolismo , Fenóis/sangue , Gravidez , Efeitos Tardios da Exposição Pré-Natal/genética , RNA/genética , RNA/metabolismo , Ovinos , Gordura Subcutânea/crescimento & desenvolvimento , Gordura Subcutânea/metabolismo
17.
PLoS One ; 15(4): e0231927, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32343751

RESUMO

Metabolic Syndrome (MS) is characterized by a low-grade inflammatory state causing an alteration of non-invasive indexes derived from blood count, namely monocyte-to-HDL ratio (MHR), neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), lymphocyte-to-monocyte ratio (LMR). We analyse a population of 771 subjects (394 controls and 377 MS patients) to evaluate the best predictive index of MS. The diagnosis of MS was made according to the 2006 criteria of the International Diabetes Federation (IDF). We performed ROC curve analyses to evaluate the best predictor index of MS. MHR cut-off value was used to classify the population in two different groups and to create the outcome variable of the Recursive Partitioning and Amalgamation (RECPAM) analysis. This method is a tree-structured approach that defines "risk profiles" for each group of dichotomous variables. We showed that MHR index is significantly linked to body mass index (BMI), waist circumference, creatinine, C-reactive protein (CRP), Erythrocyte Sedimentation Rate (ESR). ROC curve defined an MHR cut-off value of 6.4, which was able to identify two patient groups with significant differences in waist circumference, blood pressure, creatinine, estimated glomerular filtration rate and fasting plasma glucose. RECPAM analysis demonstrated that gender, BMI categorization and hyperglycaemia were the most important risk determinants of increased MHR index that can be considered bona fide a useful and easily obtainable tool to suggest the presence of peculiar metabolic features that predict MS.


Assuntos
Glicemia/análise , Índice de Massa Corporal , Lipoproteínas HDL/sangue , Síndrome Metabólica/patologia , Monócitos/citologia , Adulto , Idoso , Área Sob a Curva , Sedimentação Sanguínea , Proteína C-Reativa/análise , Estudos de Casos e Controles , Feminino , Humanos , Modelos Logísticos , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/metabolismo , Pessoa de Meia-Idade , Curva ROC , Fatores Sexuais , Fumantes , Circunferência da Cintura
18.
Lancet Child Adolesc Health ; 4(5): 359-369, 2020 05.
Artigo em Inglês | MEDLINE | ID: mdl-32333883

RESUMO

BACKGROUND: Primordial and primary prevention is the cornerstone for cardiometabolic health. In the randomised, controlled Special Turku Coronary Risk Factor Intervention Project (STRIP; n=1116), a 20-year dietary counselling intervention was given to children biannually from infancy, and cardiometabolic health benefits had been observed among the participants in the intervention group. Here, we report on the key results of the first follow-up done 6 years after the end of the intervention, at age 26 years. METHODS: The randomised controlled STRIP study recruited children at age 5 months from well-baby clinics in Turku, Finland, and randomly assigned them to either an intervention or control group; group allocation was unmasked. The intervention introduced participants to a heart-healthy diet, characterised by low proportional intake of saturated fat and cholesterol, by dietary counselling and nutrition education sessions to parents and children from the age of 7 months to 20 years. Children in the control group received only the basic health education given at Finnish well-baby clinics and school health care. We assessed diet, lifestyle, and cardiometabolic risk factor data, including blood pressure, anthropometry, serum biochemistry (lipids, apolipoproteins, glucose, and insulin), and homoeostatic model assessment of insulin resistance (HOMA-IR) in the participants at age 26 years. FINDINGS: 1116 children were included in the original STRIP study, of whom 551 provided data at the age 26 years follow-up, and data for 507 participants were analysed (243 in the intervention group and 264 in the control group). At follow-up, those who had been in the intervention group had slightly lower mean intake of saturated fat as a proportion of total energy intake than the control group (13·0% [SD 3·3] vs 13·7% [3·6], p=0·049). A higher proportion of participants in the intervention group achieved the targeted monounsaturated and polyunsaturated fat to saturated fat ratio of more than 2:1 than the control group (78 [39%] of 200 vs 70 [30%] of 235; risk ratio [RR] 1·16 [95% CI 1·01-1·33]; p=0·035). A higher proportion of intervention group participants met the ideal total cholesterol concentration of less than 5·17 mmol/L (194 [81%] of 240 vs 187 [72%] of 261; RR 1·45 [1·05-2·01], p=0·024) and optimal LDL cholesterol concentration of less than 3·0 mmol/L (166 [69%] of 240 vs 158 [61%] of 251; RR 1·30 [1·03-1·66], p=0·031). Those who received the intervention had lower glucose (5·00 mmol/L [SD 0·43] vs 5·07 mmol/L [0·46], p=0·040) and HOMA-IR (median 1·44 [IQR 1·09-1·91] vs 1·62 [1·22-2·09], p=0·037) than the participants in the control group. INTERPRETATION: Previously observed intervention effects during the 20-year counselling were largely maintained into adulthood 6 years after the withdrawal of the intervention. Dietary counselling introduced in infancy thus provided a sustained benefit to diet quality and cardiometabolic risk factor levels. FUNDING: Academy of Finland, Juho Vainio Foundation, Finnish Foundation for Cardiovascular Research, Finnish Ministry of Education and Culture, Finnish Cultural Foundation, Sigrid Jusélius Foundation, Special Governmental grants for Health Sciences Research (Turku University Hospital), Yrjö Jahnsson Foundation, Finnish Medical Foundation, and Turku University Foundation.


Assuntos
Doenças Cardiovasculares/prevenção & controle , Aconselhamento/métodos , Dieta Saudável/métodos , Síndrome Metabólica/prevenção & controle , Adulto , Glicemia/metabolismo , Pressão Sanguínea , Doenças Cardiovasculares/metabolismo , Colesterol/metabolismo , Colesterol na Dieta , LDL-Colesterol/metabolismo , Gorduras na Dieta , Gorduras Insaturadas na Dieta , Ingestão de Energia , Feminino , Finlândia , Seguimentos , Humanos , Insulina/metabolismo , Resistência à Insulina , Estudos Longitudinais , Masculino , Síndrome Metabólica/metabolismo , Prevenção Primária/métodos , Fatores de Risco
19.
Metabolism ; 108: 154246, 2020 07.
Artigo em Inglês | MEDLINE | ID: mdl-32333937

RESUMO

INTRODUCTION: 11ß-hydroxysteroid dehydrogenase type 1 (11ß-HSD1) is an intracellular enzyme that catalyses conversion of cortisone into cortisol; correspondingly, 11ß-HSD1 inhibitors inhibit this conversion. This systematic review focuses on the use of 11ß-HSD1 inhibitors in diseases known to be associated with abnormalities in hypothalamic pituitary adrenal (HPA) axis function. METHODS: The databases screened for suitable papers were: MedLine, EMBASE, Web of Science, ClinicalTrials.gov, and Cochrane Central. RESULTS: 1925 papers were identified, of which 29 were included in the final narrative synthesis. 11ß-HSD1 and its inhibitors have been studied in diabetes, obesity, metabolic syndrome (MetS), and Alzheimer's disease (AD). Higher expression of 11ß-HSD1 is seen in obesity and MetS, but has not yet been described in obesity or AD. Genetic studies identify 11ß-HSD1 SNPs of interest in populations with diabetes, MetS, and AD. One phase II trial successfully reduced HbA1c in a diabetic population, however trials in MetS, obesity, and AD have not met primary endpoints. CONCLUSIONS: Translation of this research from preclinical studies has proved challenging so far, however this is a growing area of research and more studies should focus on understanding the complex relationships between 11ß-HSD1 and disease pathology, especially given the therapeutic potential of 11ß-HSD1 inhibitors in development.


Assuntos
11-beta-Hidroxiesteroide Desidrogenase Tipo 1/antagonistas & inibidores , Doença de Alzheimer/metabolismo , Síndrome Metabólica/metabolismo , Doença de Alzheimer/tratamento farmacológico , Animais , Ensaios Clínicos Fase II como Assunto , Humanos , Síndrome Metabólica/tratamento farmacológico
20.
PLoS One ; 15(4): e0230769, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32259832

RESUMO

Bottlenose dolphins (Tursiops truncatus) are long-lived mammals that can develop chronic aging-associated conditions similar to humans, including metabolic syndrome. Initial studies suggest that these conditions may be attenuated in dolphins using a modified fish diet. Serum metabolomics, fatty acid panels, and blood-based health indices were compared between 20 dolphins on a modified, 50% wild-type diet (50% mullet, 25% capelin, and 25% squid and/or herring) and 10 dolphins on a baseline diet (75% capelin and 25% squid and/or herring). Blood samples were collected at Months 0, 1, 3 and 6. Dolphins on the modified diet had lower insulin (7.5 ± 4.0 and 14.8 ± 14.0 µIU/ml, P = 0.039), lower cholesterol (160 ± 26 and 186 ± 24 mg/dl, P = 0.015) and higher hematocrit (46 ± 3 and 44 ± 3%, P = 0.043) by Month 1 compared to controls. Dolphins with anemia (hemoglobin ≤ 12.5 g/dl, n = 6) or low-normal hemoglobin (12.5-13.5 g/dl, n = 3) before placed on the modified diet had normal hemoglobin concentrations (> 13.5 g/dl) by Month 3. The modified diet caused a significant shift in the metabolome, which included 664 known metabolites. Thirty prioritized metabolites at Months 1 and 3 were 100% predictive of dolphins on the modified diet. Among 25 prioritized lipids, 10 (40%) contained odd-chain saturated fatty acids (OCFAs); C15:0 was the highest-prioritized OCFA. Increased dietary intake of C15:0 (from 1.3 ± 0.4 to 4.5 ± 1.1 g/day) resulted in increased erythrocyte C15:0 concentrations (from 1.5 ± 0.3 to 5.8 ± 0.8 µg/ml, P < 0.0001), which independently predicted raised hemoglobin. Further, increasing age was associated with declining serum C15:0 (R2 = 0.14, P = 0.04). While higher circulating OCFAs have been previously associated with lower risks of cardiometabolic diseases in humans, further studies are warranted to assess potential active roles of OCFAs, including C15:0, in attenuating anemia.


Assuntos
Anemia/etiologia , Anemia/metabolismo , Golfinho Nariz-de-Garrafa/sangue , Golfinho Nariz-de-Garrafa/metabolismo , Ácidos Graxos/metabolismo , Peixes/sangue , Peixes/metabolismo , Metaboloma/fisiologia , Animais , Colesterol/metabolismo , Dieta/métodos , Feminino , Masculino , Síndrome Metabólica/genética , Síndrome Metabólica/metabolismo
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA