RESUMO
BACKGROUND: Obesity is a metabolic disease that affects many individuals around the world, related to imbalance between energy consumption and expenditure, which can lead to comorbidities. A healthy diet can significantly contribute to the prevention or treatment of this condition. Jabuticaba is an emerging fruit presenting a wide range of bioactive compounds and is being extensively studied due to its effects on lipid metabolism. The aim of this study was to evaluate the jabuticaba extract in the anxious-like behavior and in the lipid and oxidative metabolism in the context of obesity. METHODS: Forty male Wistar rats divided into five groups were used. The animals received a standard diet and/or a hypercaloric diet and after 60 days of induction, interventions were carried out with jabuticaba extract (5% and 10%) via gavage for 30 days. RESULTS: It can be observed that the jabuticaba extract was able to reverse the anxious behavior observed in obese animals and modulate parameters of lipid and oxidative metabolism. We observed a reduction in cholesterol and triglyceride levels compared to obese animals. Furthermore, we observed an improvement in oxidative parameters, with a reduction in protein carbonylation in the liver and modulation of antioxidant enzymes such as superoxide dismutase and catalase. Contrary to expectations, we did not observe changes in leptin, adiponectin and tumor necrosis factor alpha (TNF-α) levels. CONCLUSION: Our work demonstrates that jabuticaba extract can improve metabolic, oxidative and behavioral changes in animals with obesity. © 2024 Society of Chemical Industry.
Assuntos
Myrtaceae , Obesidade , Extratos Vegetais , Ratos Wistar , Animais , Masculino , Obesidade/metabolismo , Obesidade/tratamento farmacológico , Obesidade/dietoterapia , Ratos , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/administração & dosagem , Myrtaceae/química , Metabolismo dos Lipídeos/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Humanos , Frutas/química , Dieta Hiperlipídica/efeitos adversos , Triglicerídeos/metabolismo , Leptina/metabolismo , Leptina/sangue , Comportamento Animal/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos , Colesterol/metabolismo , Colesterol/sangue , Superóxido Dismutase/metabolismo , Biomarcadores/metabolismoRESUMO
Aim: To evaluate the applicability of Limulus amebocyte lysate (LAL) assay for endotoxin determination in lipid compounding liposomal nanoformulations.Materials & methods: Spiked cholesterol, hydrogenated soy phosphatidylcholine and 1,2-distearoyl-sn-glycero-3-phosphoethanolamine-N-[amino(polyethylene glycol)-2000] (DSPE-PEG 2000) samples with endotoxins, simulating contaminated samples or in-process contamination were analyzed by chromogenic LAL assay.Results: Recovery of spiked endotoxins was achieved from DSPE-PEG 2000 suspended in water, whereas recovery was not achieved from spiked cholesterol and hydrogenated soy phosphatidylcholine suspended in methanol, and from multilamellar vesicles.Conclusion: Endotoxins, when in contact with organic solvents, no longer react in the LAL assay as they do in aqueous media. This indicates limitations of the LAL assay for endotoxin control in raw materials for liposomal nanoformulations.
[Box: see text].
Assuntos
Endotoxinas , Teste do Limulus , Lipossomos , Lipossomos/química , Endotoxinas/análise , Teste do Limulus/métodos , Polietilenoglicóis/química , Fosfatidilcolinas/química , Colesterol/química , Colesterol/análise , Animais , Fosfatidiletanolaminas/químicaRESUMO
In daily clinical practice, cardiologists are confronted with patients with HIV/AIDS and this population needs special attention due to their higher cardiovascular risk. Studies show an increase in cardiovascular disease (CVD) among people with HIV/AIDS and one of the main causes of death in this group. HIV is associated with dyslipidaemia and endothelial damage, which have been proposed as a cause of the increased risk of events, and HIV replication is a determining factor in endothelial dysfunction. With antiretroviral therapy (ART) there has been a reduction in morbidity and mortality from HIV/AIDS, however, several studies have shown an increase risk factors for CVD in this population, both in individuals on ART and those not on it. Two high-impact studies related to cardiovascular risk in the HIV population are Start and Smart. Studies are important for understanding this occurrence and its relationship with the presence of the virus and the use of antiretroviral therapy in this population. In view of the higher cardiovascular risk of these patients and the question of whether they deserve a different cholesterol target from other populations. METHODS: A retrospective, observational study was carried out on a sample of HIV patients from the Brazilian STD/AIDS Reference Centre (CRT), selected by lottery using their registration number, from 1 January 2011 to February 2023, aged over 18. 148 medical records were assessed and the following were collected population characteristics. DISCUSSION: the CRT data were compared with the Start and Smart studies. The Reprieve study showed benefits earlier than expected with patients receiving a statin. An interim analysis revealed a 35 per cent reduction in serious adverse cardiovascular events in the statin group, leading to the placebo group stopping earlier. The viral load varied between the studies, with CRT having an average of 500,000 copies/ml, Start 12,759 copies/ml and Smart less than 400 copies/ml. Studies have associated HIV infection and higher viral loads with impaired endothelial function and vasodilation. Despite the data in the literature, all the patients with heart disease had undetected viral loads and CD4+ cell counts above 500 cells/mm³. Those with a high viral load in the study were not the ones with CVD. CONCLUSIONS: In CRT, the percentage of primary events attributable to serious conditions unrelated to AIDS was 1.3 per cent. Analysing biomarkers could elucidate the effects of antiretroviral therapy on arterial disease. Another fact that probably justifies the low occurrence of cardiovascular and cerebral events in CRT is the multidisciplinary care given to patients, providing intensive primary and secondary prevention through counselling and follow-up. We suggest better control of cardiovascular risk factors with multi-professional intervention and more aggressive targets for the control of comorbidities.
Assuntos
Doenças Cardiovasculares , Colesterol , Síndrome da Imunodeficiência Adquirida , Inibidores de Hidroximetilglutaril-CoA Redutases , Fatores de Risco de Doenças Cardíacas , HIV , Contagem de Linfócito CD4RESUMO
BACKGROUND: Capsaicin, a bioactive compound found in peppers, is recognized for its anti-inflammatory, antioxidant, and anti-lipidemic properties. This study aimed to evaluate the effects of capsaicin on atherosclerosis progression. METHODS: Apolipoprotein E knockout mice and their C57BL/6 controls were utilized to assess blood lipid profile, inflammatory status, and atherosclerotic lesions. We also examined the influence of capsaicin on cholesterol influx and efflux, and the role of TRPV1 and PPARγ signaling pathways in bone marrow-derived macrophages. RESULTS: Capsaicin treatment reduced weight gain, visceral adiposity, blood triglycerides, and total and non-HDL cholesterol. These improvements were associated with a reduction in atherosclerotic lesions in the aorta and carotid. Capsaicin also improved hepatic oxidative and inflammatory status. Systemic inflammation was also reduced, as indicated by reduced leukocyte rolling and adhesion on the mesenteric plexus. Capsaicin decreased foam cell formation by reducing cholesterol influx through scavenger receptor A and increasing cholesterol efflux via ATP-binding cassette transporter A1, an effect primarily linked to TRPV1 activation. CONCLUSIONS: These findings underscore the potential of capsaicin as a promising agent for atherosclerosis prevention, highlighting its comprehensive role in modulating lipid metabolism, foam cell formation, and inflammatory responses.
Assuntos
Aterosclerose , Capsaicina , Células Espumosas , Inflamação , PPAR gama , Canais de Cátion TRPV , Animais , Masculino , Camundongos , Anti-Inflamatórios/farmacologia , Aterosclerose/prevenção & controle , Aterosclerose/tratamento farmacológico , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Capsaicina/farmacologia , Colesterol/sangue , Colesterol/metabolismo , Células Espumosas/efeitos dos fármacos , Células Espumosas/metabolismo , Inflamação/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Knockout , Camundongos Knockout para ApoE , PPAR gama/metabolismo , Transdução de Sinais/efeitos dos fármacos , Canais de Cátion TRPV/metabolismoRESUMO
Triacontanol is a long-chain primary alcohol derived from policosanol, known for its diverse biological activities, including functioning as a plant growth regulator and exhibiting anti-inflammatory and antitumoral effects. However, its application is limited due to its high hydrophobicity, resulting in poor absorption and reduced therapeutic effectiveness. A potential solution to this problem is the use of niosomes. Niosomes are carriers composed of non-ionic surfactants, cholesterol, charge-inducing agents, and a hydration medium. They are effective in encapsulating drugs, improving their solubility and bioavailability. The objective of this study was to optimize and synthesize nano-niosomes for the encapsulation of triacontanol. Niosomes were synthesized using a thin-film hydration method combined with ultrasonication, following a Box-Behnken design. Niosomes were characterized using various techniques including dynamic light scattering, Fourier-transform infrared spectroscopy (FTIR), confocal microscopy, high-resolution scanning electron microscopy, and transmission electron microscopy (TEM). Formulation 14 of niosomes achieved the desired size, polydispersity index (0.198 ± 0.008), and zeta potential (-31.28 ± 1.21). FTIR analysis revealed a characteristic signal in the 3400-300 cm-1 range, indicating intermolecular interactions due to a bifurcated hydrogen bond between cholesterol and S60. Confocal microscopy confirmed the presence of triacontanol through Nile Red fluorescence. TEM revealed the spherical structure of niosomes.
Assuntos
Álcoois Graxos , Lipossomos , Lipossomos/química , Álcoois Graxos/química , Tamanho da Partícula , Espectroscopia de Infravermelho com Transformada de Fourier , Nanopartículas/química , Portadores de Fármacos/química , Solubilidade , Composição de Medicamentos/métodos , Colesterol/química , Tensoativos/químicaRESUMO
Visceral cestodiases, like cysticercoses and echinococcoses, are caused by cystic larvae from parasites of the Cestoda class and are endemic or hyperendemic in many areas of the world. Current therapeutic approaches for these diseases are complex and present limitations and risks. Therefore, new safer and more effective treatments are urgently needed. The Niemann-Pick C1 (NPC1) protein is a cholesterol transporter that, based on genomic data, would be the solely responsible for cholesterol uptake in cestodes. Considering that human NPC1L1 is a known target of ezetimibe, used in the treatment of hypercholesterolemia, it has the potential for repurposing for the treatment of visceral cestodiases. Here, phylogenetic, selective pressure and structural in silico analyses were carried out to assess NPC1 evolutive and structural conservation, especially between cestode and human orthologs. Two NPC1 orthologs were identified in cestode species (NPC1A and NPC1B), which likely underwent functional divergence, leading to the loss of cholesterol transport capacity in NPC1A. Comparative interaction analyses performed by molecular docking of ezetimibe with human NPC1L1 and cestode NPC1B pointed out to similarities that consolidate the idea of cestode NPC1B as a target for the repurposing of ezetimibe as a drug for the treatment of visceral cestodiases.
Assuntos
Cestoides , Ezetimiba , Proteína C1 de Niemann-Pick , Ezetimiba/farmacologia , Ezetimiba/uso terapêutico , Humanos , Animais , Proteína C1 de Niemann-Pick/metabolismo , Cestoides/metabolismo , Cestoides/efeitos dos fármacos , Cestoides/genética , Filogenia , Simulação de Acoplamento Molecular , Reposicionamento de Medicamentos/métodos , Simulação por Computador , Colesterol/metabolismo , Proteínas de Membrana Transportadoras/metabolismo , Proteínas de Membrana Transportadoras/química , Proteínas de Membrana Transportadoras/genética , Peptídeos e Proteínas de Sinalização Intracelular/metabolismo , Peptídeos e Proteínas de Sinalização Intracelular/genética , Peptídeos e Proteínas de Sinalização Intracelular/química , Anticolesterolemiantes/farmacologia , Anticolesterolemiantes/uso terapêuticoRESUMO
BACKGROUND: Obesity and various biochemical parameters, including triglycerides, cholesterol, glucose, C-reactive protein, and estimated glomerular filtration rate, have been linked to elevated uric acid (UA) levels in populations with normal kidney function due to decreased UA excretion and/or increased UA synthesis. However, it remains unclear whether all these factors exhibit similar associations with UA levels in clinical populations characterized by compromised renal function, such as kidney transplant patients (KTPs). OBJECTIVE: To evaluate whether serum UA levels are associated with body adiposity and biochemical parameters in KTPs. METHODS: A cross-sectional study involving 113 KTPs was conducted. Body fat was estimated using bioelectrical impedance, and waist circumference was measured using an inelastic tape. Serum levels of UA, creatinine, glucose, triglycerides, total cholesterol, and its fractions were measured using the colorimetric method. C-reactive protein levels were assessed using the immunoturbidimetric method, and urea levels were determined via enzymatic kinetics. Glomerular filtration rate was estimated using the chronic kidney disease epidemiology collaboration equation. Linear regression analyses were employed to assess the association between serum UA levels and body adiposity as well as biochemical parameters, while adjusting for confounders. RESULTS: Serum UA levels exhibited a positive association with creatinine (ß = 0.402; p = 0.013) and urea (ß = 0.024; p = 0.001), while demonstrating an inverse association with estimated glomerular filtration rate (ß = -0.030; p < 0.001). However, serum UA levels were not significantly associated with fat mass (both in kilograms and as a percentage), waist circumference, triglycerides, C-reactive protein, glucose, HDL cholesterol, LDL cholesterol, VLDL cholesterol, or total cholesterol. CONCLUSION: Serum UA levels are only associated with biochemical parameters linked to renal function in KTPs. Consequently, in individuals with suboptimal renal function, such as KTPs, UA does not exhibit associations with other biochemical parameters and body adiposity, as commonly observed in non-renal disease populations.
Assuntos
Adiposidade , Proteína C-Reativa , Taxa de Filtração Glomerular , Transplante de Rim , Ácido Úrico , Humanos , Ácido Úrico/sangue , Masculino , Estudos Transversais , Feminino , Pessoa de Meia-Idade , Adulto , Proteína C-Reativa/metabolismo , Creatinina/sangue , Triglicerídeos/sangue , Obesidade/sangue , Glicemia/metabolismo , Circunferência da Cintura , Colesterol/sangue , Ureia/sangue , Índice de Massa CorporalRESUMO
BACKGROUND: This study evaluated the expression of ACE and ACE2 in the placenta and white adipose tissue in lean and obese women, and correlated their levels with anthropometric, clinical, and laboratory parameters, and tissue count of inflammatory cells. METHODS: A cross-sectional analytical study was performed with 49 pregnant women and their respective newborns. Samples of placenta and adipose tissue were used for measuring mRNA expression for ACE and ACE2 through qRT-PCR. Inflammatory cell counting was performed through conventional microscopy. RESULTS: An increase in ACE expression and a decrease in ACE2 were observed in the placenta and adipose tissue of women with obesity. ACE2 levels showed a negative correlation with pre-pregnancy BMI and total cholesterol. CONCLUSION: Maternal obesity can modulate the expression of RAS components in the placenta and white adipose tissue, with ACE2 correlated with pre-pregnancy BMI and total cholesterol.
Assuntos
Tecido Adiposo Branco , Enzima de Conversão de Angiotensina 2 , Índice de Massa Corporal , Obesidade , Peptidil Dipeptidase A , Placenta , Humanos , Feminino , Gravidez , Placenta/metabolismo , Enzima de Conversão de Angiotensina 2/genética , Enzima de Conversão de Angiotensina 2/metabolismo , Peptidil Dipeptidase A/genética , Peptidil Dipeptidase A/metabolismo , Adulto , Estudos Transversais , Obesidade/genética , Obesidade/metabolismo , Tecido Adiposo Branco/metabolismo , Colesterol/metabolismo , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Obesidade Materna/metabolismo , Obesidade Materna/genética , Recém-NascidoRESUMO
MicroRNAs (miRs) are small non-coding RNAs that regulate gene expression post-transcriptionally and are crucial in lipid metabolism. ATP-binding cassette transporter A1 (ABCA1) is essential for cholesterol efflux from cells to high-density lipoprotein (HDL). Dysregulation of miRs targeting ABCA1 can affect cholesterol homeostasis and contribute to coronary artery disease (CAD). This study aimed to investigate the expression of miRs targeting ABCA1 in human monocytes, their role in cholesterol efflux, and their relationship with CAD. We included 50 control and 50 CAD patients. RT-qPCR examined the expression of miR-33a-5p, miR-26a-5p, and miR-144-3p in monocytes. Logistic regression analysis explored the association between these miRs and CAD. HDL's cholesterol acceptance was analyzed using the J774A.1 cell line. Results showed that miR-26a-5p (p = 0.027) and ABCA1 (p = 0.003) expression levels were higher in CAD patients, while miR-33a-5p (p < 0.001) levels were lower. Downregulation of miR-33a-5p and upregulation of ABCA1 were linked to a lower CAD risk. Atorvastatin upregulated ABCA1 mRNA, and metformin downregulated miR-26a-5p in CAD patients. Decreased cholesterol efflux correlated with higher CAD risk and inversely with miRs in controls. Reduced miR-33a-5p expression and increased ABCA1 expression are associated with decreased CAD risk. miR deregulation in monocytes may influence atherosclerotic plaque formation by regulating cholesterol efflux. Atorvastatin and metformin could offer protective effects by modulating miR-33a-5p, miR-26a-5p, and ABCA1, suggesting potential therapeutic strategies for CAD prognosis and treatment.
Assuntos
Transportador 1 de Cassete de Ligação de ATP , Doença da Artéria Coronariana , MicroRNAs , Humanos , MicroRNAs/genética , MicroRNAs/metabolismo , Transportador 1 de Cassete de Ligação de ATP/genética , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Doença da Artéria Coronariana/genética , Doença da Artéria Coronariana/metabolismo , Doença da Artéria Coronariana/sangue , Masculino , Feminino , Pessoa de Meia-Idade , Leucócitos Mononucleares/metabolismo , Regulação da Expressão Gênica , Idoso , Linhagem Celular , Colesterol/metabolismo , Colesterol/sangue , Monócitos/metabolismoRESUMO
Most patients with schizophrenia (SCZ) do not exhibit violent behaviors and are more likely to be victims rather than perpetrators of violent acts. However, a subgroup of forensic detainees with SCZ exhibit tendencies to engage in criminal violations. Although numerous models have been proposed, ranging from substance use, serotonin transporter gene, and cognitive dysfunction, the molecular underpinnings of violence in SCZ patients remains elusive. Lithium and clozapine have established anti-aggression properties and recent studies have linked low cholesterol levels and ultraviolet (UV) radiation with human aggression, while vitamin D3 reduces violent behaviors. A recent study found that vitamin D3, omega-3 fatty acids, magnesium, and zinc lower aggression in forensic population. In this review article, we take a closer look at aryl hydrocarbon receptor (AhR) and the dysfunctional lipidome in neuronal membranes, with emphasis on cholesterol and vitamin D3 depletion, as sources of aggressive behavior. We also discuss modalities to increase the fluidity of neuronal double layer via membrane lipid replacement (MLR) and natural or synthetic compounds. This article is part of the Special Issue on "Personality Disorders".
Assuntos
Antipsicóticos , Esquizofrenia , Humanos , Esquizofrenia/metabolismo , Antipsicóticos/uso terapêutico , Colesterol/metabolismo , Animais , Colecalciferol/metabolismo , Agressão/fisiologia , Agressão/efeitos dos fármacosRESUMO
There is scarce information about the effect of sperm morphology and seminal plasma composition on cat semen freezability. Thus, this study aims to assess the effect of cat sperm morphology and seminal plasma cholesterol (CHOL) and triacylglyceride (TAG) concentrations on sperm post-thaw survival. Ejaculates (n = 49) were evaluated, and seminal plasma was separated and frozen until CHOL and TAG concentrations were measured. The sperm pellet was diluted in a tris-based egg yolk extender, frozen (n = 38), or processed for sperm ultrastructure study (n = 11). Abnormalities recorded were abnormal head shape and size, detached heads, knobbed or ruffled acrosomes, eccentric mid-piece insertion, proximal and distal cytoplasmic droplets, folded and coiled tails, and Dag defect. Ultramicroscopic evaluation detected several sperm abnormalities in fresh semen and some sperm damage in frozen semen. Seminal plasma lipids components were positively correlated with post-thaw motility and acrosome integrity. Higher freezability indices for motility and acrosome integrity were observed in frozen-thawed semen with high seminal plasma CHOL and TAG concentrations. No freezability differences were observed between teratozoospermic and normozoospermic ejaculates. Our results showed that even when seminal plasma was removed before cryopreservation, sperm survival after thawing was significantly higher in samples with high seminal plasma CHOL and TAG concentrations, indicating a rapid adherence to these compounds to the sperm plasma membrane, protecting sperm cells from temperature changes. Nevertheless, there were no differences in sperm freezability by sperm morphology.
Assuntos
Colesterol , Criopreservação , Preservação do Sêmen , Sêmen , Espermatozoides , Triglicerídeos , Animais , Masculino , Gatos , Sêmen/química , Colesterol/sangue , Preservação do Sêmen/veterinária , Triglicerídeos/sangue , Criopreservação/veterinária , Análise do Sêmen/veterinária , Motilidade dos EspermatozoidesRESUMO
The present study aimed to establish zebrafish as an experimental model for investigations into obesity and physical exercise, as well as to assess the effects of these factors on metabolism. The experiment spanned twelve weeks, comprising a feeding trial during which the last four weeks incorporated a physical exercise protocol. This protocol involved placing fifteen animals in a five-liter aquarium, where they were subjected to swimming at an approximate speed of 0.08 m/s for 30 min daily. Throughout the experiment, histological analyses of visceral, subcutaneous, and hepatic adipose tissues were conducted, along with biochemical analyses of total cholesterol and its fractions, triglycerides, glucose, lactate, and alanine aminotransferase (ALT) levels. Additionally, oxidative stress markers, such as reactive oxygen species (ROS) levels, superoxide dismutase (SOD) activity, and catalase activity and the formation of thiobarbituric acid-reactive substances, were investigated. The results revealed that the group fed a high-fat diet exhibited an increase in ROS production and SOD activity. In contrast, the group administered the high-fat diet and subjected to physical exercise demonstrated a notable reduction in visceral adipocyte area, hepatic steatosis levels, ALT levels, and SOD activity. These findings indicate that physical exercise has a positive effect on obesity and oxidative stress in zebrafish, providing promising evidence for future investigations in this field.
Assuntos
Dieta Hiperlipídica , Estresse Oxidativo , Condicionamento Físico Animal , Espécies Reativas de Oxigênio , Superóxido Dismutase , Peixe-Zebra , Animais , Condicionamento Físico Animal/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Superóxido Dismutase/metabolismo , Fígado/metabolismo , Masculino , Tecido Adiposo/metabolismo , Triglicerídeos/metabolismo , Triglicerídeos/sangue , Alanina Transaminase/sangue , Alanina Transaminase/metabolismo , Catalase/metabolismo , Obesidade/metabolismo , Natação , Colesterol/metabolismo , Colesterol/sangueRESUMO
The objective of the study was to evaluate the effect of the inclusion of cocoa bran in the diet of lambs and its effect on reproductive parameters. For this, 40 lambs were randomly assigned to four treatments, and including 0, 10, 20 and 30% levels of cocoa bran in the concentrate. Blood was collected to measure cholesterol and testosterone and semen for physical and morphological evaluation; testicular biometry and morphometry were also evaluated. There was significant difference (P < 0.05) in body weight and tubulosomatic index between the lambs in the control treatment and those in the 30% cocoa bran treatment. There was no difference in testicular biometry, physical and morphological parameters of fresh semen, testicular morphometry, and volumetric ratio between lambs in all the treatments (P < 0.05). In addition, there was no difference in plasma cholesterol or testosterone concentration (P > 0.05). Thus, it is possible to include up to 30% of cocoa bran in diet without affecting the reproductive parameters of lambs.
Assuntos
Ração Animal , Colesterol , Dieta , Carneiro Doméstico , Testículo , Testosterona , Animais , Masculino , Ração Animal/análise , Dieta/veterinária , Testículo/anatomia & histologia , Carneiro Doméstico/fisiologia , Testosterona/sangue , Colesterol/sangue , Colesterol/análise , Cacau/química , Reprodução , Sêmen/fisiologia , Fenômenos Fisiológicos da Nutrição Animal , Distribuição Aleatória , Ovinos/fisiologiaRESUMO
PURPOSE OF REVIEW: This review aims to critically examine how VLCKD affects plasma lipoprotein, lipid and cholesterol metabolism. Cardiovascular disease is a worldwide health problem affecting millions of people and leading to high rates of mortality and morbidity. There is a well-established association between cardiovascular disease and circulating cholesterol. Various dietary recommendations are currently available for the management of dyslipidemia. RECENT FINDINGS: The very low-calorie ketogenic diet (VLCKD) is becoming increasingly popular as a treatment option for several pathological conditions, including dyslipidemia. In addition to being low in calories, the VLCKD's main feature is its unique calorie distribution, emphasizing a reduction in carbohydrate consumption in favor of fat as the primary calorie source. Lowering calorie intake through a VLCKD can reduce the endogenous production of cholesterol. However, if the foods consumed are from animal sources, dietary cholesterol intake may increase due to the higher fat content of animal products. When combined, these dietary practices may have opposing effects on plasma cholesterol levels. Studies investigating the impact of VLCKD on plasma cholesterol and low-density lipoprotein cholesterol levels report contradictory findings. While some studies found an increase in low-density lipoprotein cholesterol levels, others showed a decrease in total cholesterol and low-density lipoprotein cholesterol, along with an increase in high-density lipoprotein cholesterol.
Assuntos
Restrição Calórica , Dieta Cetogênica , Metabolismo dos Lipídeos , Humanos , Dislipidemias/dietoterapia , Colesterol/sangue , Ingestão de Energia , Doenças Cardiovasculares/prevenção & controle , Doenças Cardiovasculares/dietoterapia , Colesterol na Dieta , LDL-Colesterol/sangueRESUMO
In this study, we evaluated the impact of incorporating diblock and triblock amphiphilic copolymers, as well as cholesterol into DPPC liposomes on the release of a model molecule, calcein, mediated by exogenous phospholipase A2 activity. Our findings show that calcein release slows down in the presence of copolymers at low concentration, while at high concentration, the calcein release profile resembles that of the DPPC control. Additionally, calcein release mediated by exogenous PLA2 decreases as the amount of solubilized cholesterol increases, with a maximum between 18 mol% and 20 mol%. At concentrations higher than 24 mol%, no calcein release was observed. Studies conducted on HEK-293 and HeLa cells revealed that DPPC liposomes reduced viability by only 5% and 12%, respectively, after 3 hours of incubation, while DPPC liposome in presence of 33 mol% of Cholesterol reduced viability by approximately 11% and 23%, respectively, during the same incubation period. For formulations containing copolymers at low and high concentrations, cell viability decreased by approximately 20% and 40%, respectively, after 3 hours of incubation. Based on these preliminary results, we can conclude that the presence of amphiphilic copolymers at low concentration can be used in the design of new DPPC liposomes, and together with cholesterol, they can modulate liposome stabilization. The new formulations showed low cytotoxicity in HEK-293 cells, and it was observed that calcein release depended entirely on PLA2 activity and the presence of calcium ions.
Assuntos
1,2-Dipalmitoilfosfatidilcolina , Sobrevivência Celular , Colesterol , Fluoresceínas , Lipossomos , Fosfolipases A2 , Humanos , Lipossomos/química , Fosfolipases A2/metabolismo , Fosfolipases A2/química , Fluoresceínas/química , Células HEK293 , Colesterol/química , Colesterol/metabolismo , Sobrevivência Celular/efeitos dos fármacos , 1,2-Dipalmitoilfosfatidilcolina/química , Células HeLa , Polímeros/química , Polímeros/farmacologia , Liberação Controlada de FármacosRESUMO
Cholesterol is crucial for the proper functioning of eukaryotic cells, especially neurons, which rely on cholesterol to maintain their complex structure and facilitate synaptic transmission. However, brain cells are isolated from peripheral cholesterol by the blood-brain barrier and mature neurons primarily uptake the cholesterol synthesized by astrocytes for proper function. This study aimed to investigate the effect of aging on cholesterol trafficking in astrocytes and its delivery to neurons. We found that aged astrocytes accumulated high levels of cholesterol in the lysosomal compartment, and this cholesterol buildup can be attributed to the simultaneous occurrence of two events: decreased levels of the ABCA1 transporter, which impairs ApoE-cholesterol export from astrocytes, and reduced expression of NPC1, which hinders cholesterol release from lysosomes. We show that these two events are accompanied by increased microR-33 in aged astrocytes, which targets ABCA1 and NPC1. In addition, we demonstrate that the microR-33 increase is triggered by oxidative stress, one of the hallmarks of aging. By coculture experiments, we show that cholesterol accumulation in astrocytes impairs the cholesterol delivery from astrocytes to neurons. Remarkably, we found that this altered transport of cholesterol could be alleviated through treatment with endocannabinoids as well as cannabidiol or CBD. Finally, according to data demonstrating that aged astrocytes develop an A1 phenotype, we found that cholesterol buildup is also observed in reactive C3+ astrocytes. Given that reduced neuronal cholesterol affects synaptic plasticity, the ability of cannabinoids to restore cholesterol transport from aged astrocytes to neurons holds significant implications in aging and inflammation.
Assuntos
Transportador 1 de Cassete de Ligação de ATP , Astrócitos , Canabinoides , Colesterol , Lisossomos , Neurônios , Astrócitos/metabolismo , Astrócitos/efeitos dos fármacos , Animais , Colesterol/metabolismo , Neurônios/metabolismo , Neurônios/efeitos dos fármacos , Lisossomos/metabolismo , Lisossomos/efeitos dos fármacos , Transportador 1 de Cassete de Ligação de ATP/metabolismo , Canabinoides/farmacologia , Canabinoides/metabolismo , Células Cultivadas , Proteína C1 de Niemann-Pick , Camundongos , Envelhecimento/metabolismo , Técnicas de Cocultura , Camundongos Endogâmicos C57BLRESUMO
INTRODUCTION: Despite strong evidences supporting the protective role of exercise against stress-induced repercussions, the literature remains inconclusive regarding metabolic aspects. Therefore, this study aimed to evaluate the effect of Physical Training (PT) by swimming on the metabolic parameters of rats subjected to restraint stress. METHODS: Wistar rats (n = 40) were divided into four groups: Control (C), Trained (T), Stressed (S), and Trained/Stressed (TS). The restraint stress protocol involved confining the animals in PVC pipes for 60 minutes/day for 12 weeks. Concurrently, the swimming PT protocol was performed without additional load in entailed sessions of 60 minutes conducted five days a week for the same duration. The following parameters were analyzed: fitness progression assessed by the physical capacity test, body mass, serum level of glucose, triglyceride, cholesterol and corticosterone, as well as glycemic tolerance test, evaluated after glucose administration (2 g/kg, i.p.). RESULTS: Trained groups (T and TS) exhibited enhanced physical capacity (169 ± 21 and 162 ± 22% increase, respectively) compared to untrained groups (C: 9 ± 5 and S: 11 ± 13% increase). Corticosterone levels were significantly higher in the S group (335 ± 9 nmoL/L) compared to C (141 ± 3 nmoL/L), T (174 ± 3 nmoL/L) and TS (231 ± 7 nmoL/L), which did not differ from each other. There were no significant changes in serum glucose, cholesterol, and triglyceride levels among the groups. However, the glycemic curve after glucose loading revealed increased glycemia in the S group (area under curve 913 ± 30 AU) but the TS group exhibited values (673 ± 12 AU) similar to the groups C (644 ± 10 AU) and T (649 ± 9 AU). CONCLUSION: Swimming-based training attenuated stress-induced corticosterone release and prevented glucose intolerance in rats, reinforcing the importance of exercise as a potential strategy to mitigate the pathophysiological effects of stress.
Assuntos
Glicemia , Corticosterona , Condicionamento Físico Animal , Ratos Wistar , Restrição Física , Estresse Psicológico , Natação , Animais , Condicionamento Físico Animal/fisiologia , Masculino , Corticosterona/sangue , Glicemia/análise , Natação/fisiologia , Estresse Psicológico/metabolismo , Colesterol/sangue , Ratos , Triglicerídeos/sangue , Fatores de Tempo , Teste de Tolerância a Glucose , Distribuição Aleatória , Metaboloma/fisiologiaRESUMO
Obesity increases serum triglycerides and decreases high-density lipoprotein cholesterol (HDL-C). The objective is to explore some functions of HDL, cholesterol transfers and antioxidant, in subjects with grade I (G1-OB) and III (G3-OB) obesity and effects of bariatric surgery on G3-OB. Fifteen G3-OB patients (43 ± 6 years, BMI 49 ± 3 kg/m2) were studied before and 1 year after bariatric surgery; 15 G1-OB (32 ± 2 years, 32 ± 2 kg/m2) and 15 normal weight (NW) (38 ± 6 years, 22 ± 1 kg/m2) were also studied. HDL diameter, cholesterol transfer to HDL and antioxidant capacity of HDL were determined. G3-OB had higher triglycerides and lower HDL-C; G1-OB had higher triglycerides than NW but HDL-C was equal. Compared to NW, HDL size was smaller in G3-OB but equal in G1-OB. One year after bariatric surgery, BMI and triglycerides of G3-OB decreased (p < .0001 and p = .0012, respectively) and HDL-C increased (p < .0001), equalling of NW group. Antioxidant capacity and cholesterol transfers were not different in groups and were unchanged 1 year after bariatric surgery in G3-OB. HDL antioxidant capacity and transfer of cholesterol to HDL were not defective in obesity despite HDL-C reduction and smaller HDL size. In addition, pronounced weight loss by bariatric surgery did not change those protective functions.
Assuntos
Cirurgia Bariátrica , HDL-Colesterol , Obesidade , Redução de Peso , Humanos , Adulto , Masculino , Feminino , Pessoa de Meia-Idade , Obesidade/cirurgia , Obesidade/metabolismo , HDL-Colesterol/sangue , HDL-Colesterol/metabolismo , Lipoproteínas HDL/sangue , Lipoproteínas HDL/metabolismo , Colesterol/sangue , Triglicerídeos/sangue , Índice de Massa Corporal , Obesidade Mórbida/cirurgia , Obesidade Mórbida/metabolismo , Obesidade Mórbida/sangue , Antioxidantes/metabolismoRESUMO
This study evaluated the growth and physiological response of proactive and reactive Colossoma macropomum juveniles in a recirculating aquaculture system (RAS). In Phase 1 of the experiment (50 days of cultivation), juveniles, weighing 2.16 ± 0.52 g, were stocked in 12 28-L tanks to test the following treatments: proactive (PT), reactive (RT) and mixed (MT) composed of reactive (MRT) and proactive (MPT) animals. In Phase 2 of the experiment (40 days of cultivation), the animals were transferred to 175-L tanks with the same treatments as Phase 1. The animals were fed twice a day with commercial diet during both phases. After Phase 1, MPT animals showed higher growth than MRT animals (P < 0.05), and higher weight gain and daily weight than PT animals (P < 0.05). After Phase 2, PT animals showed higher weight gain and daily weight gain than RT and MT animals (P < 0.05), as did MPT animals compared to PT animals. Performance for RT animals was superior (P < 0.05) to that of MRT animals. Glucose (P < 0.04) and cholesterol (P < 0.01) were higher for RT animals compared to PT animals. Cholesterol was higher for MPT animals compared to MRT animals (P < 0.01), while plasma protein was lower (P < 0.001). Glucose (P < 0.001) and cholesterol (P < 0.01) were higher for MPT animals compared to PT animals and for MRT animals compared to RT animals (glucose P < 0.02, cholesterol P < 0.01). After 90 days of cultivation, proactive animals cultivated separately presented better performance. When cultivated together, reactive animals experienced a decrease in performance and both stress coping styles showed more signs of stress.
Assuntos
Aquicultura , Animais , Aquicultura/métodos , Caraciformes/fisiologia , Caraciformes/crescimento & desenvolvimento , Aumento de Peso , Colesterol/sangue , Colesterol/análise , Ração Animal/análise , Dieta/veterináriaRESUMO
Cholesterol-rich nanoemulsion (LDE) can carry chemotherapeutic agents in the circulation and can concentrate those agents in the neoplastic and inflammatory tissues. This method improves the biodistribution of the drug and reduces toxicity. However, the structural stability of LDE particles, without or with associated drugs, has not been extensively investigated. The aim of the present study is to investigate the structural stability of LDE and LDE associated to paclitaxel, etoposide or methotrexate in aqueous solution over time by small-angle X-ray scattering (SAXS and Ultra SAXS) and dynamic light scattering (DLS). The results show that LDE and LDE associated with those chemotherapeutic agents had reproducible and stable particle diameter, physical structure, and aggregation behavior over 3-month observation period. As estimated from both DLS and Ultra-SAXS methods, performed at pre-established intervals, the average particle diameter of LDE alone was approx. 32â¯nm, of LDE-paclitaxel was 31â¯nm, of LDE-methotrexate was 35â¯nm and of LDE-etoposide was 36â¯nm. Ultra-SAXS analysis showed that LDE nanoparticles were quasi-spherical, and SAXS showed that drug molecules inside the particles showed a layered-like organization. Formulations of LDE with associated PTX, ETO or MTX were successfully tested in animal experiments and in patients with cancer or with cardiovascular disease, showing markedly low toxicity, good tolerability and possible superior pharmacological action. Our results may be useful for ensuing clinical trials of this novel Nanomedicine tool, by strengthening the knowledge of the structural aspects of those LDE formulations.