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1.
PLoS One ; 16(10): e0258617, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34653200

RESUMO

BACKGROUND: It has been shown that vitamin D is associated with obesity and the development of atherosclerosis. Less is known about this association among adolescents with obesity. OBJECTIVES: To determine the association of vitamin D level and metabolic risk factors with carotid intima-media thickness (CIMT) among obese adolescents. METHODS: We conducted a cross-sectional study among obese children aged 15 to 17 years in Yogyakarta, Indonesia. The association of vitamin D and other metabolic risk factors (triglyceride, low-density lipoprotein cholesterol (LDL-C) and high-density lipoprotein cholesterol (HDL-C), and insulin resistance using homeostasis model assessment of insulin resistance (HOMA-IR)) with CIMT was explored by multivariable linear regression models. RESULTS: Out of 156 obese adolescents, 55.8% were boys. Compared to girls, boys had higher BMI z-score, waist circumference, and HDL-cholesterol. After adjustment for age, sex and second-hand smoke exposure, high HOMA-IR, total cholesterol, LDL-cholesterol and triglyceride levels were associated with higher odds of elevated CIMT. In analyses stratified by sex, a similar trend was observed in boys, while none of the risk factors were associated with CIMT in girls. We observed no association between vitamin D and CIMT. CONCLUSIONS: Hyperinsulinemia, higher total cholesterol and LDL cholesterol were associated with greater odds of elevated CIMT among obese adolescent boys.


Assuntos
Aterosclerose/diagnóstico por imagem , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Obesidade Pediátrica/complicações , Triglicerídeos/metabolismo , Adolescente , Aterosclerose/etiologia , Aterosclerose/metabolismo , Espessura Intima-Media Carotídea , Estudos Transversais , Feminino , Humanos , Indonésia , Resistência à Insulina , Masculino , Obesidade Pediátrica/diagnóstico por imagem , Obesidade Pediátrica/metabolismo , Caracteres Sexuais , Vitamina D
2.
Int J Mol Sci ; 22(19)2021 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-34638860

RESUMO

(1) Background: Sepsis is one of the most common critical care illnesses with increasing survivorship. The quality of life in sepsis survivors is adversely affected by several co-morbidities, including increased incidence of dementia, stroke, cardiac disease and at least temporary deterioration in cognitive dysfunction. One of the potential explanations for their progression is the persistence of lipid profile abnormalities induced during acute sepsis into recovery, resulting in acceleration of atherosclerosis. (2) Methods: This is a targeted review of the abnormalities in the long-term lipid profile abnormalities after sepsis; (3) Results: There is a well-established body of evidence demonstrating acute alteration in lipid profile (HDL-c ↓↓, LDL-C -c ↓↓). In contrast, a limited number of studies demonstrated depression of HDL-c levels with a concomitant increase in LDL-C -c in the wake of sepsis. VLDL-C -c and Lp(a) remained unaltered in few studies as well. Apolipoprotein A1 was altered in survivors suggesting abnormalities in lipoprotein metabolism concomitant to overall lipoprotein abnormalities. However, most of the studies were limited to a four-month follow-up and patient groups were relatively small. Only one study looked at the atherosclerosis progression in sepsis survivors using clinical correlates, demonstrating an acceleration of plaque formation in the aorta, and a large metanalysis suggested an increase in the risk of stroke or acute coronary event between 3% to 9% in sepsis survivors. (4) Conclusions: The limited evidence suggests an emergence and persistence of the proatherogenic lipid profile in sepsis survivors that potentially contributes, along with other factors, to the clinical sequel of atherosclerosis.


Assuntos
Aterosclerose/metabolismo , Colesterol/metabolismo , Lipoproteínas/metabolismo , Sepse/metabolismo , Apolipoproteínas/metabolismo , Aterosclerose/complicações , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Progressão da Doença , Humanos , Sepse/complicações , Triglicerídeos/metabolismo
3.
PLoS One ; 16(10): e0258768, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34665828

RESUMO

Psoriasis is a chronic inflammatory skin disease that affects approximately 125 million people worldwide. It has significant impacts on both physical and emotional health-related quality of life comparable to other major illnesses. Accurately prediction of psoriasis using biomarkers from routine laboratory tests has important practical values. Our goal is to derive a powerful predictive model for psoriasis disease based on only routine hospital tests. We collected a data set including 466 psoriasis patients and 520 healthy controls with 81 variables from only laboratory routine tests, such as age, total cholesterol, HDL cholesterol, blood pressure, albumin, and platelet distribution width. In this study, Boruta feature selection method was applied to select the most relevant features, with which a Random Forest model was constructed. The model was tested with 30 repetitions of 10-fold cross-validation. Our classification model yielded an average accuracy of 86.9%. 26 notable features were selected by Boruta, among which 15 features are confirmed from previous studies, and the rest are worth further investigations. The experimental results demonstrate that the machine learning approach has good potential in predictive modeling for the psoriasis disease given the information only from routine hospital tests.


Assuntos
Biomarcadores/metabolismo , Colesterol/metabolismo , Psoríase/diagnóstico , Albumina Sérica Humana/metabolismo , Adolescente , Adulto , Distribuição por Idade , Idoso , Idoso de 80 Anos ou mais , Algoritmos , Estudos de Casos e Controles , Criança , Pré-Escolar , HDL-Colesterol/metabolismo , Testes Diagnósticos de Rotina , Feminino , Humanos , Lactente , Aprendizado de Máquina , Masculino , Pessoa de Meia-Idade , Psoríase/metabolismo , Qualidade de Vida , Adulto Jovem
4.
Int J Med Sci ; 18(15): 3533-3543, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34522180

RESUMO

Importance: Despite the availability of a vaccine against the severe acute respiratory syndrome-coronavirus-2 (SARS-CoV-2), humans will have to live with this virus and the after-effects of the coronavirus disease 2019 (COVID-19) infection for a long time. Cholesterol plays an important role in the infection and prognosis of SARS-CoV-2, and the study of its mechanism is of great significance not only for the treatment of COVID-19 but also for research on generic antiviral drugs. Observations: Cholesterol promotes the development of atherosclerosis by activating NLR family pyrin domain containing 3 (NLRP3), and the resulting inflammatory environment indirectly contributes to COVID-19 infection and subsequent deterioration. In in vitro studies, membrane cholesterol increased the number of viral entry sites on the host cell membrane and the number of angiotensin-converting enzyme 2 (ACE2) receptors in the membrane fusion site. Previous studies have shown that the fusion protein of the virus interacts with cholesterol, and the spike protein of SARS-CoV-2 also requires cholesterol to enter the host cells. Cholesterol in blood interacts with the spike protein to promote the entry of spike cells, wherein the scavenger receptor class B type 1 (SR-B1) plays an important role. Because of the cardiovascular protective effects of lipid-lowering therapy and the additional anti-inflammatory effects of lipid-lowering drugs, it is currently recommended to continue lipid-lowering therapy for patients with COVID-19, but the safety of extremely low LDL-C is questionable. Conclusions and Relevance: Cholesterol can indirectly increase the susceptibility of patients to SARS-CoV-2 and increase the risk of death from COVID-19, which are mediated by NLRP3 and atherosclerotic plaques, respectively. Cholesterol present in the host cell membrane, virus, and blood may also directly participate in the virus cell entry process, but the specific mechanism still needs further study. Patients with COVID-19 are recommended to continue lipid-lowering therapy.


Assuntos
COVID-19/complicações , Hipercolesterolemia/complicações , Enzima de Conversão de Angiotensina 2/metabolismo , Antivirais/uso terapêutico , Aterosclerose/fisiopatologia , COVID-19/diagnóstico , COVID-19/tratamento farmacológico , COVID-19/terapia , Membrana Celular/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Endocitose , Humanos , Hipercolesterolemia/diagnóstico , Hipercolesterolemia/terapia , Inflamação , Macrófagos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/sangue , Prognóstico , SARS-CoV-2 , Receptores Depuradores Classe B/metabolismo
5.
Arterioscler Thromb Vasc Biol ; 41(11): 2708-2725, 2021 11.
Artigo em Inglês | MEDLINE | ID: mdl-34551590

RESUMO

Objective: To investigate the role of adipocyte Pcpe2 (procollagen C-endopeptidase enhancer 2) in SR-BI (scavenger receptor class BI)-mediated HDL-C (high-density lipoprotein cholesterol) uptake and contributions to adipose lipid storage. Approach and Results: Pcpe2, a glycoprotein devoid of intrinsic proteolytic activity, is believed to participate in extracellular protein-protein interactions, supporting SR-BI- mediated HDL-C uptake. In published studies, Pcpe2 deficiency increased the development of atherosclerosis by reducing SR-BI-mediated HDL-C catabolism, but the biological impact of this deficiency on adipocyte SR-BI-mediated HDL-C uptake is unknown. Differentiated cells from Ldlr-/-/Pcpe2-/- (Pcpe2-/-) mouse adipose tissue showed elevated SR-BI protein levels, but significantly reduced HDL-C uptake compared to Ldlr-/- (control) adipose tissue. SR-BI-mediated HDL-C uptake was restored by preincubation of cells with exogenous Pcpe2. In diet-fed mice lacking Pcpe2, significant reductions in visceral, subcutaneous, and brown adipose tissue mass were observed, despite elevations in plasma triglyceride and cholesterol concentrations. Significant positive correlations exist between adipose mass and Pcpe2 expression in both mice and humans. Conclusions: Overall, these findings reveal a novel and unexpected function for Pcpe2 in modulating SR-BI expression and function as it relates to adipose tissue expansion and cholesterol balance in both mice and humans.


Assuntos
Adipócitos/metabolismo , Aterosclerose/metabolismo , HDL-Colesterol/metabolismo , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Microdomínios da Membrana/metabolismo , Obesidade/metabolismo , Receptores Depuradores Classe B/metabolismo , Gordura Subcutânea/metabolismo , Adipócitos/patologia , Adipogenia , Adiposidade , Adulto , Animais , Aterosclerose/genética , Aterosclerose/patologia , Células CHO , Caveolina 1/metabolismo , Cricetulus , Dieta Hiperlipídica , Modelos Animais de Doenças , Metabolismo Energético , Proteínas da Matriz Extracelular/genética , Proteínas da Matriz Extracelular/metabolismo , Feminino , Glicoproteínas/genética , Humanos , Mediadores da Inflamação/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Microdomínios da Membrana/genética , Microdomínios da Membrana/patologia , Camundongos Endogâmicos C57BL , Camundongos Knockout , Pessoa de Meia-Idade , Obesidade/genética , Obesidade/patologia , Receptores de LDL/genética , Receptores de LDL/metabolismo , Receptores Depuradores Classe B/genética , Gordura Subcutânea/patologia
6.
PLoS One ; 16(9): e0257574, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34547056

RESUMO

Metabolic syndrome (MetS) is characterized by adiposity and atherogenic dyslipidemia consisting of elevated triglyceride and decreased high density lipoprotein cholesterol (HDL-C) levels however, cholesterol concentration alone does not reflect HDL functionality. Cholesterol efflux capacity (CEC) captures a key anti-atherosclerotic function of HDL; studies linking CEC to MetS have yielded inconsistent findings and lacked racial/ethnic diversity. The aim of this study was to evaluate the association between CEC and MetS in a large multi-ethnic population utilizing two different CEC assays interrogating overlapping but distinct reverse cholesterol transport pathways. A cross-sectional study was performed using the Dallas Heart Study cohort and cholesterol efflux was measured with radiolabeled and fluorescent cholesterol assays. The relationship between CEC and MetS was assessed using multivariable regression analyses. A total of 2241 participants were included (mean age was 50 years; 38% men and 53% Blacks). CEC was independently and inversely associated with MetS irrespective of efflux assay (CEC-radiolabeled, adjusted OR 0·71 [95% CI 0·65-0·80]. CEC-fluorescent, adjusted OR 0·85 [95% CI 0·77-0·94]). Both CEC measures were inversely associated with waist circumference and directly associated with HDL-C but not with other MetS components. There was an interaction by sex but not by race such that the inverse associations between CEC and MetS were somewhat attenuated in men (OR 0·86, 95%CI 0·74-1·01). In this large multi-ethnic cohort, impaired CEC is linked to MetS irrespective of efflux assay and race/ethnicity but less so among men. Future studies are needed to assess whether CEC mediates the atherosclerotic cardiovascular disease risk of MetS.


Assuntos
Colesterol/metabolismo , Síndrome Metabólica/epidemiologia , Adulto , Aterosclerose/etiologia , Colesterol/sangue , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Estudos Transversais , Grupos Étnicos , Feminino , Humanos , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/etnologia , Síndrome Metabólica/patologia , Pessoa de Meia-Idade , Razão de Chances , Prevalência , Fatores de Risco , Fatores Sexuais , Circunferência da Cintura
7.
Science ; 373(6553)2021 07 23.
Artigo em Inglês | MEDLINE | ID: mdl-34437091

RESUMO

The biogenesis of high-density lipoprotein (HDL) requires apoA1 and the cholesterol transporter ABCA1. Although the liver generates most of the HDL in the blood, HDL synthesis also occurs in the small intestine. Here, we show that intestine-derived HDL traverses the portal vein in the HDL3 subspecies form, in complex with lipopolysaccharide (LPS)-binding protein (LBP). HDL3, but not HDL2 or low-density lipoprotein, prevented LPS binding to and inflammatory activation of liver macrophages and instead supported extracellular inactivation of LPS. In mouse models involving surgical, dietary, or alcoholic intestinal insult, loss of intestine-derived HDL worsened liver injury, whereas outcomes were improved by therapeutics that elevated and depended upon raising intestinal HDL. Thus, protection of the liver from injury in response to gut-derived LPS is a major function of intestinally synthesized HDL.


Assuntos
Intestino Delgado/metabolismo , Lipoproteínas HDL3/metabolismo , Hepatopatias/prevenção & controle , Fígado/metabolismo , Veia Porta/metabolismo , Proteínas de Fase Aguda/metabolismo , Adulto , Animais , Proteínas de Transporte/metabolismo , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Enterócitos/metabolismo , Humanos , Intestino Delgado/cirurgia , Macrófagos do Fígado/imunologia , Macrófagos do Fígado/metabolismo , Receptores de Lipopolissacarídeos/metabolismo , Lipopolissacarídeos/metabolismo , Lipoproteínas HDL3/sangue , Fígado/patologia , Cirrose Hepática/patologia , Cirrose Hepática/prevenção & controle , Hepatopatias/patologia , Receptores X do Fígado/metabolismo , Glicoproteínas de Membrana/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Ligação Proteica , Transdução de Sinais , Receptor 4 Toll-Like/metabolismo
8.
Arterioscler Thromb Vasc Biol ; 41(10): e453-e467, 2021 10.
Artigo em Inglês | MEDLINE | ID: mdl-34380332

RESUMO

Objective: Overall and atherosclerosis-associated mortality is elevated in humans with very high HDL (high-density lipoprotein) cholesterol concentrations. Mice with a deficiency of the HDL receptor, Scarb1 (scavenger receptor class B type 1), are a robust model of this phenotype and exhibit several additional pathologies. We hypothesized that the previously reported high plasma concentration of free cholesterol (FC)-rich HDL in Scarb1-/- mice produces a state of high HDL-FC bioavailability that increases whole-body FC and dysfunction in multiple tissue sites. Approach and Results: The higher mol% FC in Scarb1-/- versus WT (wild type) HDL (41.1 versus 16.0 mol%) affords greater FC bioavailability for transfer to multiple sites. Plasma clearance of autologous HDL-FC mass was faster in WT versus Scarb1-/- mice. FC influx from Scarb1-/- HDL to LDL (low-density lipoprotein) and J774 macrophages was greater ([almost equal to]4x) than that from WT HDL, whereas FC efflux capacity was similar. The higher mol% FC of ovaries, erythrocytes, heart, and macrophages of Scarb1-/- versus WT mice is associated with previously reported female infertility, impaired cell maturation, cardiac dysfunction, and atherosclerosis. The FC contents of other tissues were similar in the two genotypes, and these tissues were not associated with any overt pathology. In addition to the differences between WT versus Scarb1-/- mice, there were many sex-dependent differences in tissue-lipid composition and plasma FC clearance rates. Conclusions: Higher HDL-FC bioavailability among Scarb1-/- versus WT mice drives increased FC content of multiple cell sites and is a potential biomarker that is mechanistically linked to multiple pathologies.


Assuntos
Aterosclerose/metabolismo , Colesterol/metabolismo , Macrófagos/metabolismo , Receptores Depuradores Classe B/deficiência , Animais , Aterosclerose/genética , Aterosclerose/patologia , Disponibilidade Biológica , Linhagem Celular , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Feminino , Humanos , Cinética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Knockout , Fenótipo , Placa Aterosclerótica , Receptores Depuradores Classe B/genética , Fatores Sexuais , Distribuição Tecidual
9.
Int J Mol Sci ; 22(14)2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34298929

RESUMO

Dyslipidemia is characterized by increasing plasma levels of low-density lipoprotein-cholesterol (LDL-C), triglycerides (TGs) and TG-rich lipoproteins (TGRLs) and is a major risk factor for the development of atherosclerotic cardiovascular disorders (ASCVDs). It is important to understand the metabolic mechanisms underlying dyslipidemia to develop effective strategies against ASCVDs. Angiopoietin-like 3 (ANGPTL3), a member of the angiopoietin-like protein family exclusively synthesized in the liver, has been demonstrated to be a critical regulator of lipoprotein metabolism to inhibit lipoprotein lipase (LPL) activity. Genetic, biochemical, and clinical studies in animals and humans have shown that loss of function, inactivation, or downregulated expression of ANGPTL3 is associated with an obvious reduction in plasma levels of TGs, LDL-C, and high-density lipoprotein-cholesterol (HDL-C), atherosclerotic lesions, and the risk of cardiovascular events. Therefore, ANGPTL3 is considered an alternative target for lipid-lowering therapy. Emerging studies have focused on ANGPTL3 inhibition via antisense oligonucleotides (ASOs) and monoclonal antibody-based therapies, which have been carried out in mouse or monkey models and in human clinical studies for the management of dyslipidemia and ASCVDs. This review will summarize the current literature on the important role of ANGPTL3 in controlling lipoprotein metabolism and dyslipidemia, with an emphasis on anti-ANGPTL3 therapies as a potential strategy for the treatment of dyslipidemia and ASCVDs.


Assuntos
Proteínas Semelhantes a Angiopoietina/metabolismo , Dislipidemias/metabolismo , Lipoproteínas/metabolismo , Animais , Aterosclerose/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol , Humanos , Triglicerídeos/metabolismo
10.
Nat Commun ; 12(1): 4434, 2021 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-34290249

RESUMO

Dyslipidemia is a main driver of cardiovascular diseases. The ability of macrophages to scavenge excess lipids implicate them as mediators in this process and understanding the mechanisms underlying macrophage lipid metabolism is key to the development of new treatments. Here, we investigated how adipose tissue macrophages regulate post-prandial cholesterol transport. Single-cell RNA sequencing and protected bone marrow chimeras demonstrated that ingestion of lipids led to specific transcriptional activation of a population of resident macrophages expressing Lyve1, Tim4, and ABCA1. Blocking the phosphatidylserine receptor Tim4 inhibited lysosomal activation and the release of post-prandial high density lipoprotein cholesterol following a high fat meal. Both effects were recapitulated by chloroquine, an inhibitor of lysosomal function. Moreover, clodronate-mediated cell-depletion implicated Tim4+ resident adipose tissue macrophages in this process. Thus, these data indicate that Tim4 is a key regulator of post-prandial cholesterol transport and adipose tissue macrophage function and may represent a novel pathway to treat dyslipidemia.


Assuntos
Transportador 1 de Cassete de Ligação de ATP/metabolismo , Tecido Adiposo/metabolismo , Colesterol/metabolismo , Macrófagos/metabolismo , Proteínas de Membrana/metabolismo , Período Pós-Prandial/fisiologia , Tecido Adiposo/citologia , Animais , HDL-Colesterol/metabolismo , Dieta Hiperlipídica , Metabolismo dos Lipídeos , Lisossomos/metabolismo , Macrófagos/citologia , Camundongos , Obesidade/metabolismo , Obesidade/patologia , Ativação Transcricional , Proteínas de Transporte Vesicular/metabolismo
11.
Crit Rev Biochem Mol Biol ; 56(4): 426-439, 2021 08.
Artigo em Inglês | MEDLINE | ID: mdl-34182846

RESUMO

Plasma levels of high-density lipoprotein (HDL) inversely correlate with the incidence of cardiovascular diseases (CVD). The causal relationship between plasma HDL-cholesterol levels and CVD has been called into question by Mendelian randomization studies and the majority of clinical trials not showing any benefit of plasma HDL-cholesterol raising drugs on CVD. Nonetheless, recent Mendelian randomization studies including an increased number of CVD cases compared to earlier studies have confirmed that HDL-cholesterol levels and CVD are causally linked. Moreover, several studies in large population cohorts have shown that the cholesterol efflux capacity of HDL inversely correlates with CVD. Cholesterol efflux pathways exert anti-inflammatory and anti-atherogenic effects by suppressing proliferation of hematopoietic stem and progenitor cells, and inflammation and inflammasome activation in macrophages. Cholesterol efflux pathways also suppress the accumulation of cholesteryl esters in macrophages, i.e. macrophage foam cell formation. Recent single-cell RNASeq studies on atherosclerotic plaques have suggested that macrophage foam cells have lower expression of inflammatory genes than non-foam cells, probably reflecting liver X receptor activation, upregulation of ATP Binding Cassette A1 and G1 cholesterol transporters and suppression of inflammation. However, when these pathways are defective lesional foam cells may become pro-inflammatory.


Assuntos
Aterosclerose/metabolismo , HDL-Colesterol/metabolismo , Regulação da Expressão Gênica , RNA-Seq , Análise de Célula Única , Animais , Aterosclerose/genética , Aterosclerose/patologia , Transporte Biológico Ativo/genética , Proliferação de Células , HDL-Colesterol/genética , Células-Tronco Hematopoéticas/metabolismo , Células-Tronco Hematopoéticas/patologia , Humanos , Inflamassomos , Inflamação/genética , Inflamação/metabolismo , Inflamação/patologia , Receptores X do Fígado/genética , Receptores X do Fígado/metabolismo , Análise da Randomização Mendeliana
12.
Biomed Res Int ; 2021: 6687551, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34104650

RESUMO

In the present study, we examined the synergetic effect of forskolin and mevastatin administration on lipid profile and lipid metabolism in omental adipose tissue in dyslipidemic rats. The study was conducted on forty male albino rats. The rats were randomly classified into four main groups of ten animals in each group as follows: group A, served as control nontreated; group B, rats that received Triton WR 1339 (500 mg/kg); group C, rats that received Triton WR 1339 with forskolin (100% FSK extract 0.5 mg/kg/day) for four weeks; and group D, dyslipidemic rats received both mevastatin and forskolin. At the end of the experimental period, blood and omental adipose tissue samples were collected, preserved, and used for biochemical determination of lipid profile and mRNA expression profile of adenylate cyclase (AC), hormone-sensitive lipase, respectively (HSL), and adenosine monophosphate-activated protein kinase (AMPK). The results showed a significant decline in the serum concentration of total cholesterol, LDL-cholesterol, and triglycerides, although there was a significant increase in serum levels of HDL-cholesterol and glycerol in rats received forskolin alone or with mevastatin when compared with control and dyslipidemic groups. The mRNA expression levels of AC, HSL, and AMPK were significantly increased in omental adipose tissue of rats received forskolin when compared with other groups. In conclusion, forskolin acts synergistically with mevastatin to lower lipid profile and improve lipid metabolism in dyslipidemic rats through upregulation of AMPK expression.


Assuntos
Monofosfato de Adenosina/metabolismo , Colforsina/farmacologia , Dislipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Lipídeos/fisiologia , Lovastatina/análogos & derivados , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Animais , HDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Dislipidemias/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Lovastatina/farmacologia , Masculino , Ratos , Triglicerídeos/metabolismo , Regulação para Cima/efeitos dos fármacos
13.
Food Funct ; 12(14): 6416-6431, 2021 Jul 21.
Artigo em Inglês | MEDLINE | ID: mdl-34076000

RESUMO

Depression is an important global health issue that is associated with serious physical and mental health consequences. The field of nutritional psychiatry has generated observational and efficacy data supporting a role for healthy dietary patterns in depression. Here, we aim to evaluate the effects of high-fat diet (HFD) consumption on depressive-like behaviors. BALB/c mice were grouped randomly: control, chronic restraint stress (CRS), HFD and CRS + HFD groups. The depressive-like behavior was evaluated using behavioral tests. The serotonin content in murine brain tissue and blood lipid concentrations were detected by ELISA. The fatty acid content in the liver, adipose tissue of epididymis, brain tissue, and serum of mice was determined by gas chromatography (GC). Expression of the fatty acid synthesis pathway-related enzymes at the mRNA level was analyzed by qRT-PCR. The results indicated that a high-fat diet could promote depressive-like behavior. In comparison with regular feeding, concentrations of blood lipids were significantly changed in the HFD group. Correlation analysis implied that high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c) were closely related to depressive-like behavior. Based on fatty acid analysis, the palmitoleic acid, linoleic acid, oleic acid, and arachidonic acid content was remarkably changed in mice with depressive-like behavior. In addition, acetyl-CoA carboxylase (ACC), stearoyl-CoA desaturase-1 (SCD1), fatty acid desaturase 1 (FADS1), and fatty acid desaturase 2 (FADS2) expression, which are involved in de novo fatty acid synthesis, desaturation of fatty acids, and arachidonic acid synthesis, were strengthened in HFD mice with depressive-like behavior. Therefore, we postulated that the disorder of lipid metabolism induced by HFD consumption accelerated the development of depressive-like behavior.


Assuntos
Comportamento Animal , Depressão/etiologia , Dieta Hiperlipídica/efeitos adversos , Metabolismo dos Lipídeos , Tecido Adiposo/metabolismo , Animais , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Depressão/metabolismo , Depressão/psicologia , Ácidos Graxos/metabolismo , Lipídeos/sangue , Lipogênese , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Serotonina/metabolismo
14.
FEMS Microbiol Lett ; 368(10)2021 06 11.
Artigo em Inglês | MEDLINE | ID: mdl-34089327

RESUMO

Obesity, which is often caused by adipocyte metabolism dysfunction, is rapidly becoming a serious global health issue. Studies in the literature have shown that camellia oil (Camellia oleifera Abel) exerted potential lipid regulation and other multiple biological activities. Here, we aimed to investigate the effects of camellia oil on obese mice induced by a high-fat diet and to explore gut microbiota alterations after camellia oil intervention. The results showed that oral administration of camellia oil dramatically attenuated the fat deposits, serum levels of the total cholesterol, triacylglycerol, low-density lipoprotein cholesterol, fasting plasma glucose, the atherosclerosis index, the hepatic steatosis and inflammation in high-fat diet-induced obese mice. Meanwhile, the high-density lipoprotein cholesterol level in obese mice was enhanced after the camellia oil treatment. Furthermore, 16S rRNA analysis showed that certain aspects of the gut microbiota, especially the gut microbiota diversity and the relative abundance of Actinobacteria, Coriobacteriaceae, Lactobacillus and Anoxybacillus, were significantly increased by camellia oil treatment while the ratio of Firmicutes to Bacteroidetes was decreased. Taken together, our finding suggested that camellia oil was a potential dietary supplement and functional food for ameliorating fat deposits, hyperglycemia and fatty liver, probably by modifying the gut microbiota composition.


Assuntos
Camellia/química , Microbioma Gastrointestinal , Obesidade/dietoterapia , Obesidade/microbiologia , Óleos Vegetais/metabolismo , Animais , Bactérias/classificação , Bactérias/genética , Bactérias/isolamento & purificação , Camellia/metabolismo , Colesterol/metabolismo , HDL-Colesterol/metabolismo , Dieta Hiperlipídica/efeitos adversos , Humanos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Óleos Vegetais/química , Triglicerídeos/metabolismo
15.
PLoS One ; 16(5): e0251324, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043644

RESUMO

INTRODUCTION: The dietary carotenoids lutein (L) and zeaxanthin (Z) are transported in the bloodstream by lipoproteins, sequestered by adipose tissue, and eventually captured in the retina where they constitute macular pigment. There are no L&Z dietary intake recommendations nor desired blood/tissue concentrations for the Spanish general population. Our aim was to assess the correlation of L&Z habitual dietary intake (excluding food supplements), resulting serum concentrations and lipid profile with macular pigment optical density (MPOD) as well as the contrast sensitivity (CT), as visual outcome in normolipemic subjects (n = 101) aged 45-65. METHODS: MPOD was measured by heterochromatic flicker photometry, serum L&Z by HPLC, the dietary intake by a 3-day food records and CT using the CGT-1000-Contrast-Glaretester at six stimulus sizes, with and without glare. RESULTS: Lutein and zeaxanthin concentrations (median) in serum: 0.361 and 0.078 µmol/L, in dietary intake: 1.1 mg L+Z/day. MPOD: 0.34du. L+Z intake correlates with their serum concentrations (rho = 0.333, p = 0.001), which in turn correlates with MPOD (rho = 0.229, p = 0.000) and with fruit and vegetable consumption (rho = 0.202, p = 0.001), but not with lutein+zeaxanthin dietary intake. MPOD correlated with CT, with and without glare (rho ranges: -0.135, 0.160 and -0.121, -0.205, respectively). MPOD predictors: serum L+Z, L+Z/HDL-cholesterol (ß-coeficient: -0.91±0.2, 95%CI: -1.3,-0.5) and HDL-cholesterol (R2 = 15.9%). CT predictors: MPOD, mainly at medium and smaller visual angles (corresponding to spatial frequencies for which sensitivity declines with age) and gender (ß-coefficients ranges: -0.95,-0.39 and -0.13,-0.39, respectively). CONCLUSION: A higher MPOD is associated with a lower ratio of L+Z/HDL-cholesterol and with a lower CT (higher contrast sensitivity). The HDL-cholesterol would also act indirectly on the CT improving the visual function.


Assuntos
Sensibilidades de Contraste/efeitos dos fármacos , Ingestão de Alimentos/fisiologia , Pigmento Macular/metabolismo , HDL-Colesterol/metabolismo , Dieta , Suplementos Nutricionais , Feminino , Ofuscação , Voluntários Saudáveis , Humanos , Lipídeos/sangue , Lipoproteínas/metabolismo , Luteína/administração & dosagem , Macula Lutea/efeitos dos fármacos , Macula Lutea/metabolismo , Masculino , Pessoa de Meia-Idade , Retina/efeitos dos fármacos , Retina/metabolismo , Visão Ocular/efeitos dos fármacos , Zeaxantinas/administração & dosagem
16.
Am J Cardiol ; 151: 15-24, 2021 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-34049675

RESUMO

Statin therapy plays an important role in stabilizing and regressing coronary artery plaques. Omega-3 supplements also have anti-inflammatory and antioxidant effects on coronary plaques. However, the effect of omega-3 supplementation on the basis of statin therapy on the stability and composition of plaques, is still unclear. We searched for randomized controlled trials published prior to November 2020 in the PubMed, Embase and Cochrane databases. Finally, eight studies using different imaging techniques to evaluate coronary atherosclerotic plaque, including optical coherence tomography (OCT), coronary CT angiography (cCTA) and intravascular ultrasound (IB-IVUS), met our inclusion criteria. We pooled data extracted from the included studies using the standardized mean difference (SMD) or mean difference (MD) of the random effects model. Compared with statin treatment alone, the combined treatment further delayed the progression of total plaque volume [SMD -0.36, 95% confidence interval (CI) -0.64 to -0.08, p = 0.01] and fiber content (SMD -0.40, 95% CI -0.68 to -0.13, p = 0.004). The plasma high-sensitivity C-reactive protein (hs-CRP) level of patients in the combination treatment group was significantly lower than that of the patients in the statin treatment group alone (SMD -0.30, 95% CI -0.59 to -0.01, p = 0.04). In addition, the combined use of omega-3 further increases the fibrous cap thickness (FCT) of the plaque with an MD of 29.45 µm. There were no significant differences in plasma high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), or lipid content in plaques between the two groups. Omega-3 combined with statins is superior to the statin treatment group in stabilizing and promoting coronary plaque regression and may help to further reduce the occurrence of cardiovascular events.


Assuntos
Doença da Artéria Coronariana/tratamento farmacológico , Ácidos Graxos Ômega-3/uso terapêutico , Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , Placa Aterosclerótica/tratamento farmacológico , Proteína C-Reativa/metabolismo , HDL-Colesterol/metabolismo , LDL-Colesterol/metabolismo , Angiografia por Tomografia Computadorizada , Doença da Artéria Coronariana/diagnóstico por imagem , Quimioterapia Combinada , Humanos , Placa Aterosclerótica/diagnóstico por imagem , Ensaios Clínicos Controlados Aleatórios como Assunto , Tomografia de Coerência Óptica , Resultado do Tratamento , Ultrassonografia de Intervenção
17.
Med Sci Sports Exerc ; 53(10): 2076-2085, 2021 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-33966000

RESUMO

PURPOSES: The aims of this study were to investigate the cross-sectional and prospective associations between accelerometer-measured physical activity and cardiometabolic health in the transition to adulthood. METHODS: Data from the 1993 Pelotas (Brazil) Birth Cohort were analyzed (n = 2280). Moderate-to-vigorous intensity physical activity (MVPA) (measured using a triaxial accelerometer) and cardiometabolic health (total fat mass, blood glucose, non-high-density lipoprotein cholesterol, triglycerides, and mean resting blood pressure) were examined at age 18 and 22 yr. RESULTS: Overall, inverse dose-response associations between MVPA and cardiometabolic health at age 18 and 22 yr were observed in cross-sectional analyses of data from men and women. Prospective analyses showed that, in general, MVPA declined, and cardiometabolic health worsened in this 4-yr period in both men and women. Cardiometabolic health at age 22 yr reflected both MVPA at age 18 yr (ß, -0.007; 95% confidence interval [CI], -0.014 to 0.000) and changes in MVPA from 18 to 22 yr (ß, -0.030; 95% CI, -0.043 to -0.016) in men, but only changes in MVPA in women (ß, -0.035; 95% CI, -0.058 to -0.011). In analyses of change over time, men who improved MVPA by 20 to 30 min·d-1 showed significant improvements in cardiometabolic health over 4 yr. The magnitude of association was slightly stronger for MVPA in 10-min bouts than for MVPA accumulated in bouts of 1 min, especially in women. CONCLUSIONS: Moderate-to-vigorous intensity physical activity is an important predictor of cardiometabolic health in early adulthood. Strategies to prevent declines in MVPA at this life stage are required to prevent deteriorating cardiometabolic health profiles.


Assuntos
Acelerometria/instrumentação , Aptidão Cardiorrespiratória , Exercício Físico/fisiologia , Monitores de Aptidão Física , Adolescente , Glicemia/metabolismo , Pressão Sanguínea , Distribuição da Gordura Corporal , HDL-Colesterol/metabolismo , Estudos Transversais , Feminino , Humanos , Masculino , Estudos Prospectivos , Comportamento Sedentário , Triglicerídeos/sangue , Adulto Jovem
18.
Sci Rep ; 11(1): 9524, 2021 05 04.
Artigo em Inglês | MEDLINE | ID: mdl-33947900

RESUMO

This study was performed to evaluate the waist-to-height ratio (WHtR) distribution and assess its relationship with cardiometabolic risk in children and adolescents. A total of 8091 subjects aged 10-18 years were included from a nationally representative survey. Participants were classified into three groups: (1) < 85th, (2) ≥ 85th and < 95th, and (3) ≥ 95th percentile of WHtR. The WHtR distribution varied with sex and age. Whereas WHtR decreased from age 10-15 years in boys and from age 10-12 years in girls, it slightly increased thereafter. Compared to the < 85th percentile group, the WHtR ≥ 85th and < 95th percentile group had an odds ratio (OR) of 1.2 for elevated blood pressure (BP), 1.89 for elevated triglycerides (TGs), 1.47 for reduced high-density lipoprotein cholesterol (HDL-C) and 4.82 for metabolic syndrome (MetS). The ≥ 95th percentile group had an OR of 1.4 for elevated BP, 2.54 for elevated glucose, 2.22 for elevated TGs, 1.74 for reduced HDL-C, and 9.45 for MetS compared to the < 85th percentile group. Our results suggest that sex- and age-specific WHtR percentiles can be used as a simple clinical measurement to estimate cardiometabolic risk.


Assuntos
Estatura/fisiologia , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/fisiopatologia , Circunferência da Cintura/fisiologia , Adolescente , Pressão Sanguínea/fisiologia , Índice de Massa Corporal , Doenças Cardiovasculares/metabolismo , Criança , HDL-Colesterol/metabolismo , Feminino , Humanos , Hipertensão/metabolismo , Hipertensão/fisiopatologia , Masculino , Síndrome Metabólica/complicações , Síndrome Metabólica/metabolismo , Síndrome Metabólica/fisiopatologia , Obesidade Abdominal/complicações , Obesidade Abdominal/metabolismo , Obesidade Abdominal/fisiopatologia , Fatores de Risco , Triglicerídeos/metabolismo , Razão Cintura-Estatura
19.
Biochem Biophys Res Commun ; 556: 65-71, 2021 06 04.
Artigo em Inglês | MEDLINE | ID: mdl-33839416

RESUMO

Ethyl gallate (EG) is a well-known constituent of medicinal plants, but its effects on atherosclerosis development are not clear. In the present study, the anti-atherosclerosis effects of EG and the underlying mechanisms were explored using macrophage cultures, zebrafish and apolipoprotein (apo) E deficient mice. Treatment of macrophages with EG (20 µM) enhanced cellular cholesterol efflux to HDL, and reduced net lipid accumulation in response to oxidized LDL. Secretion of monocyte chemotactic protein-1 (MCP-1) and interleukin-6 (IL-6) from activated macrophages was also blunted by EG. Fluorescence imaging techniques revealed EG feeding of zebrafish reduced vascular lipid accumulation and inflammatory responses in vivo. Similar results were obtained in apoE-/- mice 6.5 months of age, where plaque lesions and monocyte infiltration into the artery wall were reduced by 70% and 42%, respectively, after just 6 weeks of injections with EG (20 mg/kg). HDL-cholesterol increased 2-fold, serum cholesterol efflux capacity increased by ∼30%, and the levels of MCP-1 and IL-6 were reduced with EG treatment of mice. These results suggest EG impedes early atherosclerosis development by reducing the lipid and macrophage-content of plaque. Underlying mechanisms appeared to involve HDL cholesterol efflux mechanisms and suppression of pro-inflammatory cytokine secretion.


Assuntos
Aterosclerose/tratamento farmacológico , Aterosclerose/metabolismo , Benzoatos/metabolismo , Ácido Gálico/análogos & derivados , Metabolismo dos Lipídeos/efeitos dos fármacos , Plantas Medicinais/metabolismo , Transportadores de Cassetes de Ligação de ATP/biossíntese , Transportadores de Cassetes de Ligação de ATP/genética , Animais , Apolipoproteínas E/deficiência , Aterosclerose/patologia , Aterosclerose/prevenção & controle , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Células Espumosas/citologia , Células Espumosas/efeitos dos fármacos , Células Espumosas/imunologia , Células Espumosas/metabolismo , Ácido Gálico/administração & dosagem , Ácido Gálico/metabolismo , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Inflamação/prevenção & controle , Mediadores da Inflamação/metabolismo , Camundongos , Camundongos Endogâmicos C57BL , Placa Aterosclerótica/tratamento farmacológico , Placa Aterosclerótica/metabolismo , Placa Aterosclerótica/patologia , Placa Aterosclerótica/prevenção & controle , Células RAW 264.7 , Regulação para Cima/efeitos dos fármacos , Peixe-Zebra/metabolismo
20.
Int J Mol Sci ; 22(7)2021 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-33805921

RESUMO

Colorectal cancer (CRC) is a highly prevalent malignancy with multifactorial etiology, which includes metabolic alterations as contributors to disease development. Studies have shown that lipid status disorders are involved in colorectal carcinogenesis. In line with this, previous studies have also suggested that the serum high-density lipoprotein cholesterol (HDL-C) level decreases in patients with CRC, but more recently, the focus of investigations has shifted toward the exploration of qualitative properties of HDL in this malignancy. Herein, a comprehensive overview of available evidences regarding the putative role of HDL in CRC will be presented. We will analyze existing findings regarding alterations of HDL-C levels but also HDL particle structure and distribution in CRC. In addition, changes in HDL functionality in this malignancy will be discussed. Moreover, we will focus on the genetic regulation of HDL metabolism, as well as the involvement of HDL in disturbances of cholesterol trafficking in CRC. Finally, possible therapeutic implications related to HDL will be presented. Given the available evidence, future studies are needed to resolve all raised issues concerning the suggested protective role of HDL in CRC, its presumed function as a biomarker, and eventual therapeutic approaches based on HDL.


Assuntos
Neoplasias Colorretais/metabolismo , Lipoproteínas HDL/metabolismo , Animais , Apolipoproteína A-I/metabolismo , Apolipoproteínas M/metabolismo , Arildialquilfosfatase/metabolismo , Biomarcadores/metabolismo , Carcinogênese , Colesterol/metabolismo , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , HDL-Colesterol/metabolismo , Homeostase , Humanos , Camundongos , Polimorfismo de Nucleotídeo Único , Medicina de Precisão , Receptores Depuradores Classe B/metabolismo
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