RESUMO
KEY POINTS: Fish oil (FO), rich in omega-3 polyunsaturated fatty acids, has beneficial effects on changes induced by obesity and partially prevents associated comorbidities. The effects of FO on adipocytes from different adipose tissue depots in high-fat (HF) diet induced obese mice have not been uninvestigated. This is the first study to examine the effects of FO on changes in metabolism and adipokine production in adipocytes from s.c. (inguinal; ING) or visceral (retroperitoneal; RP) white adipose depots in a HF diet-induced obese mice. Unlike most studies performed previously, FO supplementation was initiated 4 weeks before the induction of obesity. HF diet caused marked changes in ING (glucose uptake and secretion of adiponectin, tumour necrosis factor-α and interleukin-6 in ING) and RP (lipolysis, de novo lipogenesis and secretion of pro-inflammatory cytokines) adipose depots. Previous and concomitant FO administration prevented the changes in ING and RP adipocytes induced by the HF diet. ABSTRACT: In the present study, we investigated the effect of fish oil (FO) on metabolism and adipokine production by adipocytes from s.c. (inguinal; ING) and visceral (retroperitoneal; RP) white adipose depots in high-fat (HF) diet-induced obese mice. Mice were divided into CO (control diet), CO+FO, HF and HF+FO groups. The HF group presented higher body weight, glucose intolerance, insulin resistance, higher plasma total and low-density lipoprotein cholesterol levels, and greater weights of ING and RP adipose depots accompanied by hypertrophy of the adipocytes. FO exerted anti-obesogenic effects associated with beneficial effects on dyslipidaemia and insulin resistance in mice fed a HF diet (HF+FO group). HF raised RP adipocyte lipolysis and the production of pro-inflammatory cytokines and reduced de novo synthesis of fatty acids, whereas, in ING adipocytes, it decreased glucose uptake and adiponectin secretion but did not change lipolysis. Therefore, the adipose depots play different roles in HF diet-induced insulin resistance according to their location in the body. Concerning cytokine secretion, adipocytes per se in addition to white adopise tissue infiltrated leukocytes have to be considered in the aetiology of the comorbidities associated with obesity. Evidence is presented showing that previous and concomitant administration of FO can prevent changes in metabolism and the secretion of hormones and cytokines in ING and RP adipocytes induced by HF.
Assuntos
Adipócitos/efeitos dos fármacos , Adipocinas/metabolismo , Óleos de Peixe/farmacologia , Gordura Intra-Abdominal/metabolismo , Obesidade/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos/metabolismo , Animais , Células Cultivadas , Dieta Hiperlipídica/efeitos adversos , Óleos de Peixe/uso terapêutico , Interleucina-6/metabolismo , Gordura Intra-Abdominal/citologia , Gordura Intra-Abdominal/efeitos dos fármacos , Lipólise , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/tratamento farmacológico , Obesidade/etiologia , Gordura Subcutânea/citologia , Gordura Subcutânea/efeitos dos fármacos , Fator de Necrose Tumoral alfa/metabolismoRESUMO
Excess of saturated fatty acids in the diet has been associated with obesity, leading to systemic disruption of insulin signaling, glucose intolerance, and inflammation. Macadamia oil administration has been shown to improve lipid profile in humans. We evaluated the effect of macadamia oil supplementation on insulin sensitivity, inflammation, lipid profile, and adipocyte size in high-fat diet (HF) induced obesity in mice. C57BL/6 male mice (8 weeks) were divided into four groups: (a) control diet (CD), (b) HF, (c) CD supplemented with macadamia oil by gavage at 2 g/Kg of body weight, three times per week, for 12 weeks (CD + MO), and (d) HF diet supplemented with macadamia oil (HF + MO). CD and HF mice were supplemented with water. HF mice showed hypercholesterolemia and decreased insulin sensitivity as also previously shown. HF induced inflammation in adipose tissue and peritoneal macrophages, as well as adipocyte hypertrophy. Macadamia oil supplementation attenuated hypertrophy of adipocytes and inflammation in the adipose tissue and macrophages.
Assuntos
Inflamação/dietoterapia , Macadamia , Obesidade/dietoterapia , Óleos de Plantas/administração & dosagem , Adipócitos/patologia , Animais , Crescimento Celular , Colesterol/sangue , Citocinas/biossíntese , Dieta Hiperlipídica/efeitos adversos , Inflamação/metabolismo , Inflamação/patologia , Resistência à Insulina , Macrófagos Peritoneais/metabolismo , Macrófagos Peritoneais/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Óxido Nítrico/metabolismo , Obesidade/metabolismo , Obesidade/patologiaRESUMO
PURPOSE OF REVIEW: Fatty acids influence human health and diseases in various ways. In recent years, much work has been carried out to elucidate the mechanisms by which dietary fatty acids control short-term and long-term cellular functions. We have reviewed herein the most recent studies on modulation of gene expression by fatty acids. A number of genes respond to transcription factors and present a transcription factor response element in their promoter regions. Fatty acids may exert their effects on metabolism by regulating gene transcription via transcription factors. Understanding how fatty acids control expression of metabolic genes is a promising strategy to be investigated by aiming to treat metabolic diseases such as insulin resistance, obesity, and type 2 diabetes mellitus. RECENT FINDINGS: Fatty acids exert many of their biological effects through the modulation of the activity of transcription factors, such as sterol regulatory element-binding proteins, peroxisome proliferator-activated receptors, and liver X receptors. SUMMARY: Fatty acid action through transcription factors controls the expression of several inflammatory and metabolic genes.
Assuntos
Ácidos Graxos/administração & dosagem , Regulação da Expressão Gênica , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/genética , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos/efeitos dos fármacos , Receptores X do Fígado , Obesidade/tratamento farmacológico , Obesidade/genética , Receptores Nucleares Órfãos/genética , Receptores Nucleares Órfãos/metabolismo , Receptores Ativados por Proliferador de Peroxissomo/genética , Receptores Ativados por Proliferador de Peroxissomo/metabolismo , Regiões Promotoras Genéticas , Proteínas de Ligação a Elemento Regulador de Esterol/genética , Proteínas de Ligação a Elemento Regulador de Esterol/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismoRESUMO
The structural spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) plays an essential role in infection and is an important target for neutralizing antibody recognition. Mutations in the S gene can generate variants of concern (VOCs), which improve "viral fitness" through selective or survival advantages, such as increased ACE-2 receptor affinity, infectivity, viral replication, higher transmissibility, resistance to neutralizing antibodies and immune escape, increasing disease severity and reinfection risk. Five VOCs have been recognized and include B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.617.2 (India), and B.1.1.529 (multiple countries). In this review, we addressed the following critical points concerning VOCs: a) characteristics of the SARS-CoV-2 VOCs with mutations in the S gene; b) possible evasion of variants from neutralizing antibodies generated through vaccination, previous infection, or immune therapies; c) potential risk of new pandemic waves induced by the variants worldwide; and d) perspectives for further studies and actions aimed at preventing or reducing the impact of new variants during the current COVID-19 pandemic.
Assuntos
COVID-19 , SARS-CoV-2 , Anticorpos Neutralizantes , Anticorpos Antivirais , Humanos , Evasão da Resposta Imune , Mutação , PandemiasRESUMO
Background: We previously established that male Swiss mice (Mus musculus) receiving a high-fat diet (HFD) during 8 weeks exhibit similar caloric ingestion and body weight (grams) compared with mice fed a high-carbohydrate diet (HCD). HFD mice exhibit a lower inflammatory state than an HCD in the liver, skeletal muscle, and brain. In addition, we demonstrated that HFD and HCD modulated fatty acids (FA) composition in these tissues. In this study, our objective was to compare HFD mice and HCD mice in terms of systemic inflammation. Methods: Saturated FA (SFA), monounsaturated FA, omega-6 polyunsaturated FA (n-6 PUFA), and n-3 PUFA were evaluated at the time points 0, 1, 7, 14, 28, and 56 days after starting the administration of the diets. We investigated n-6 PUFA:n-3 PUFA, SFA:n-3 PUFA, palmitic acid:α-linolenic acid (ALA), and myristic acid:docosahexaenoic acid (DHA) ratios as potential serum biomarkers of systemic inflammation. We also measured the serum levels of basic fibroblast growth factor, granulocyte-macrophage colony-stimulating factor (GM-CSF), inducible protein 10 (IP-10), interferon gamma (IFN-γ), interleukin (IL)-1α, IL-1ß, IL-2, IL-4, IL-5, IL-6, IL-10, IL-13, IL-17, macrophage inflammatory protein-1α (MIP-1-α), monocyte chemotactic protein 1 (MCP-1), monokine induced by IFN-γ (MIG), and tumor necrosis factor α (TNF-α). Results: The HFD group had lower (P < 0.05) n-6 PUFA:n-3 PUFA, palmitic acid:ALA, myristic acid:DHA ratios, and lower plasma levels of proinflammatory cytokines (IFN-γ, MIG, GM-CSF, and IL-6). Conclusion: The HFD mice showed lower systemic inflammation compared with a caloric ingestion-body weight-matched control HCD mice.
Assuntos
Dieta Hiperlipídica , Carboidratos da Dieta , Inflamação , Animais , Dieta Hiperlipídica/efeitos adversos , Carboidratos da Dieta/efeitos adversos , Inflamação/epidemiologia , Masculino , CamundongosRESUMO
Aim: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). Methods: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). Results: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity CRP, IL-6, resistin and adiponectin (p < 0.05). Conclusion: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.
Assuntos
Biomarcadores/sangue , Regulação da Expressão Gênica , Inflamação/patologia , Resistência à Insulina , Síndrome Metabólica/complicações , MicroRNAs/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Proteína C-Reativa/análise , Feminino , Seguimentos , Humanos , Inflamação/sangue , Inflamação/etiologia , Masculino , MicroRNAs/sangue , Pessoa de Meia-Idade , Prognóstico , Resistina/sangue , Triglicerídeos/sangueRESUMO
We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.
Assuntos
COVID-19/epidemiologia , Brasil/epidemiologia , COVID-19/transmissão , Cidades/epidemiologia , Humanos , Modelos Estatísticos , Pandemias , SARS-CoV-2/isolamento & purificação , Fatores de TempoRESUMO
We measured plasma-derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle-aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA-Brazil). Mass spectrometry revealed decreased IGHG-1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR-141-3p and downregulation of miR-324-5p and -376c-3p compared with the NG and GI groups. The DM and GI groups showed increased miR-26b-5p expression compared with that in the NG group. The DM group showed decreased miR-374b-5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.
Assuntos
Proteínas Sanguíneas/análise , Diabetes Mellitus/sangue , Diabetes Mellitus/genética , Vesículas Extracelulares/genética , Vesículas Extracelulares/metabolismo , MicroRNAs/genética , Proteoma , Transcriptoma , Adulto , Fatores Etários , Idoso , Glicemia/análise , Brasil/epidemiologia , Diabetes Mellitus/diagnóstico , Diabetes Mellitus/epidemiologia , Perfilação da Expressão Gênica , Humanos , Incidência , Masculino , Pessoa de Meia-Idade , Proteômica , Medição de Risco , Fatores de Risco , Fatores SexuaisRESUMO
Omega-3 polyunsaturated fatty acids (n-3 PUFAs) have been reported to improve insulin sensitivity and glucose homeostasis in animal models of insulin resistance, but the involved mechanisms still remain unresolved. In this study, we evaluated the effects of fish oil (FO), a source of n-3 PUFAs, on obesity, insulin resistance and muscle mitochondrial function in mice fed a high-fat diet (HFD). C57Bl/6 male mice, 8 weeks old, were divided into four groups: control diet (C), high-fat diet (H), C+FO (CFO) and H+FO (HFO). FO was administered by oral gavage (2 g/kg b.w.), three times a week, starting 4 weeks before diet administration until the end of the experimental protocol. HFD-induced obesity and insulin resistance associated with impaired skeletal muscle mitochondrial function, as indicated by decreased oxygen consumption, tricarboxylic acid cycle intermediate (TCAi) contents (citrate, α-ketoglutarate, malate and oxaloacetate), oxidative phosphorylation protein content and mitochondrial biogenesis. These effects were associated with elevated reactive oxygen species production, decreased PGC1-a transcription and reduced Akt phosphorylation. The changes induced by the HFD were partially attenuated by FO, which decreased obesity and insulin resistance and increased mitochondrial function. In the H group, FO supplementation also improved oxygen consumption; increased TCAi content, and Akt and AMPK phosphorylation; and up-regulated mRNA expression of Gpat1, Pepck, catalase and mitochondrial proteins (Pgc1α, Pparα, Cpt1 and Ucp3). These results suggest that dietary FO attenuates the deleterious effects of the HFD (obesity and insulin resistance) by improving skeletal muscle mitochondrial function.
Assuntos
Óleos de Peixe/farmacologia , Resistência à Insulina , Mitocôndrias Musculares/fisiologia , Obesidade/dietoterapia , Adiposidade/efeitos dos fármacos , Animais , Fármacos Antiobesidade/farmacologia , Catalase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Suplementos Nutricionais , Ácidos Graxos/análise , Ácidos Graxos/metabolismo , Ácidos Graxos Ômega-3/farmacologia , Peróxido de Hidrogênio/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Mitocôndrias Musculares/efeitos dos fármacos , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/fisiologia , Obesidade/etiologia , Proteínas/genética , Proteínas/metabolismoRESUMO
The structural spike (S) glycoprotein of severe acute respiratory syndrome coronavirus-2 (SARS-CoV-2) plays an essential role in infection and is an important target for neutralizing antibody recognition. Mutations in the S gene can generate variants of concern (VOCs), which improve “viral fitness” through selective or survival advantages, such as increased ACE-2 receptor affinity, infectivity, viral replication, higher transmissibility, resistance to neutralizing antibodies and immune escape, increasing disease severity and reinfection risk. Five VOCs have been recognized and include B.1.1.7 (U.K.), B.1.351 (South Africa), P.1 (Brazil), B.1.617.2 (India), and B.1.1.529 (multiple countries). In this review, we addressed the following critical points concerning VOCs: a) characteristics of the SARS-CoV-2 VOCs with mutations in the S gene; b) possible evasion of variants from neutralizing antibodies generated through vaccination, previous infection, or immune therapies; c) potential risk of new pandemic waves induced by the variants worldwide; and d) perspectives for further studies and actions aimed at preventing or reducing the impact of new variants during the current COVID-19 pandemic.
RESUMO
We measured plasma‐derived extracellular vesicle (EV) proteins and their microRNA (miRNA) cargos in normoglycemic (NG), glucose intolerant (GI), and newly diagnosed diabetes mellitus (DM) in middle‐aged male participants of the Brazilian Longitudinal Study of Adult Health (ELSA‐Brazil). Mass spectrometry revealed decreased IGHG‐1 and increased ITIH2 protein levels in the GI group compared with that in the NG group and higher serotransferrin in EVs in the DM group than in those in the NG and GI groups. The GI group also showed increased serum ferritin levels, as evaluated by biochemical analysis, compared with those in both groups. Seventeen miRNAs were differentially expressed (DEMiRs) in the plasma EVs of the three groups. DM patients showed upregulation of miR‐141‐3p and downregulation of miR‐324‐5p and ‐376c‐3p compared with the NG and GI groups. The DM and GI groups showed increased miR‐26b‐5p expression compared with that in the NG group. The DM group showed decreased miR‐374b‐5p levels compared with those in the GI group and higher concentrations than those in the NG group. Thus, three EV proteins and five DEMiR cargos have potential prognostic importance for diabetic complications mainly associated with the immune function and iron status of GI and DM patients.
RESUMO
We propose herein a mathematical model to predict the COVID-19 evolution and evaluate the impact of governmental decisions on this evolution, attempting to explain the long duration of the pandemic in the 26 Brazilian states and their capitals well as in the Federative Unit. The prediction was performed based on the growth rate of new cases in a stable period, and the graphics plotted with the significant governmental decisions to evaluate the impact on the epidemic curve in each Brazilian state and city. Analysis of the predicted new cases was correlated with the total number of hospitalizations and deaths related to COVID-19. Because Brazil is a vast country, with high heterogeneity and complexity of the regional/local characteristics and governmental authorities among Brazilian states and cities, we individually predicted the epidemic curve based on a specific stable period with reduced or minimal interference on the growth rate of new cases. We found good accuracy, mainly in a short period (weeks). The most critical governmental decisions had a significant temporal impact on pandemic curve growth. A good relationship was found between the predicted number of new cases and the total number of inpatients and deaths related to COVID-19. In summary, we demonstrated that interventional and preventive measures directly and significantly impact the COVID-19 pandemic using a simple mathematical model. This model can easily be applied, helping, and directing health and governmental authorities to make further decisions to combat the pandemic.
Assuntos
COVID-19/epidemiologia , Surtos de Doenças/estatística & dados numéricos , Brasil/epidemiologia , COVID-19/prevenção & controle , COVID-19/transmissão , Controle de Doenças Transmissíveis/legislação & jurisprudência , Controle de Doenças Transmissíveis/estatística & dados numéricos , Surtos de Doenças/prevenção & controle , Humanos , Avaliação de Programas e Projetos de Saúde , SARS-CoV-2RESUMO
BACKGROUND/AIMS: To investigate the global changes in DNA methylation and methylation of the promoter region of the peroxisome proliferator-activated receptor gamma transcript variant 2 (Pparg2) gene resulting from a high-fat diet (HFD) and/or fish oil supplementation. METHODS: Fish oil, rich in omega-3 polyunsaturated fatty acids, or water was orally administered to male mice for 12 weeks. After the first 4 weeks, the animals were fed a control diet or an HFD until the end of the experimental protocol, when the epididymal fat, gastrocnemius muscle and liver were excised. RESULTS: Pparg2 mRNA expression was upregulated by obesity and downregulated by fish oil supplementation in the liver. In the gastrocnemius muscle, diet-induced obesity increased global DNA methylation. Fish oil prevented the decrease in Pparg2 promoter methylation induced by obesity in the gastrocnemius muscle. Regardless of the diet given, fish oil supplementation increased Pparg2 promoter methylation at CpG-263 in muscle and adipose tissue. CONCLUSION: HFD and fish oil modified global and Pparg2 promoter DNA methylation in a tissue-specific manner. Fish oil supplementation attenuated body weight gain, abolished the increase in Pparg2 expression in the liver and prevented the decrease in Pparg2 promoter methylation in the muscle induced by the HFD.
Assuntos
Metilação de DNA , Dieta Hiperlipídica/efeitos adversos , Óleos de Peixe/administração & dosagem , Músculo Esquelético/metabolismo , Tecido Adiposo/metabolismo , Animais , Suplementos Nutricionais , Ácidos Graxos Ômega-3/administração & dosagem , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Nutrigenômica , Obesidade/dietoterapia , Obesidade/genética , Obesidade/metabolismo , PPAR gama/genética , Regiões Promotoras Genéticas , Distribuição TecidualRESUMO
ABSTRACT: To explore the association of circulating miRNAs with adiposity, metabolic status and inflammatory biomarkers in patients with metabolic syndrome (MetS). METHODS: Serum levels of 372 miRNAs were measured in patients with (n = 6) and without MetS (n = 6) by quantitative PCR array, and dysregulated miRNAs were validated in a larger cohort (MetS, n = 89; non-MetS, n = 144). RESULTS: In the screening study, seven miRNAs were dysregulated in patients with MetS, and miR-421 remained increased in the validation study. miR-421 was associated with a high risk of MetS and insulin resistance and hypertension and correlated with glycated hemoglobin, triacylglycerols, high-sensitivity CRP, IL-6, resistin and adiponectin (p < 0.05). CONCLUSION: Circulating miR-421 is a potential biomarker for insulin resistance, metabolic dysregulation and inflammatory status in patients with MetS.