A obesidade está associada ao desenvolvimento de doenças crônicas não transmissíveis como hipertensão, resistência insulínica, dislipidemia e esteatose hepática. O consumo de compostos bioativos impacta na manutenção da saúde e na prevenção de risco de desenvolvimento dessas doenças. Entre os compostos bioativos, os monoterpenos são pouco investigados, apesar da literatura demonstrar efeitos promissores desses compostos sobre o metabolismo. O D-limoneno, o principal monoterpeno encontrado na laranja, é caracterizado por possuir efeitos hipolipemiantes, anti-inflamatórios e anti-obesogênicos. Estudos in vitro e in vivo descrevem sua capacidade de promover a ß-oxidação de ácidos graxos em adipócitos e redução da inflamação. Este estudo teve como objetivo investigar o efeito do D-limoneno no metabolismo e inflamação em um modelo de obesidade induzida por dieta. Para isso, quarenta camundongos machos (C57/Bl6) de 11 semanas de idade, foram distribuídos em 4 grupos, sendo que um dos grupos recebeu ração normolipídica e os demais, ração hiperlipídica. O D-limoneno foi suplementado na ração de dois grupos que receberam dieta hiperlipídica nas concentrações de 0,1%, e 0,8%. Considerando-se a ingestão alimentar dos animais, a ração suplementada com 0,1% D-limoneno correspondeu à ingestão de 0,15 g/kg/dia e ração com 0,8% de D-limoneno correspondeu a 1,3 g/kg/dia. Os animais tiveram o peso e a ingestão alimentar monitorados ao longo da intervenção com duração de 7 semanas. Os camundongos que receberam D-limoneno a 0,1% apresentaram menor ganho de peso e de acúmulo de tecido adiposo, comparado com os animais sem suplementação alimentados com a dieta hiperlipídica. Além disso, o D-limoneno promoveu a diminuição da concentração plasmática de marcadores inflamatórios incluindo TNF-α, INF-Î³ e IL-6 nos animais dos grupos que foram suplementados com D-limoneno. Entretanto, não houve diferença nos marcadores bioquímicos e metabólicos. Uma limitação do estudo foi o fato das complicações metabólicas associadas ao modelo de obesidade não terem sido plenamente estabelecidas, dados o alojamento individual, à curta duração da exposição à ração hiperlipídica e idade dos animais no início da suplementação. Esse fato pode ter dificultado a observação dos efeitos do D-limoneno na reversão dos parâmetros que seriam normalmente deteriorados pelo desenvolvimento da obesidade. Concluímos que o D-limoneno pode interferir no metabolismo energético, com possível efeito anti-obesogênico e anti-inflamatório. Devido às limitações do modelo, são necessários mais estudos para confirmar esses resultados
Obesity is associated with the development of chronic non-communicable diseases such as hypertension, insulin resistance, dyslipidemia, and hepatic steatosis. The intake of dietary bioactive compounds is associated with the maintenance of health and the prevention of chronic diseases. Among the group of bioactive compounds, monoterpenes are poorly investigated, in spite of several reports of their promising effects on metabolism. D-limonene is the main monoterpene found in oranges, known for its hypolipemic, anti-inflammatory, and anti-obesogenic effects. in vitro and in vivo studies associate D-limonene to increased ß-oxidation of fatty acids in adipocytes and reduced inflammation. This study aimed at investigating the effects of D-limonene on metabolism and inflammation in a diet-induced obesity model. For this purpose, forty male mice (C57/Bl6) were distributed in 4 groups, with one group receiving a normolipidic diet and the others, a high-fat diet. D-limonene was supplemented in the diets of two groups that received high-fat diet at the concentrations of 0.1% and 0.8%. Considering the feed intake, mice receiving D-limonene supplementation at 0.1% ingested in average 0.15 g/kg/day, while the mice receiving the supplemmentation at 0.8%, ingested approximately 1.3 g of D-limonene /kg/day. The animals had their weight and food intake monitored throughout the intervention. Mice that received Dlimonene supplementation at 0.1% showed reduced weight gain and accumulation of adipose tissue compared to the non-supplemented mice fed the high-fat diet. In addition, D-limonene promoted a decrease in hepatic inflammatory markers including TNF-α, INF-Î³, and IL-6. However, there was no difference in biochemical and metabolic markers. A limitation of the study was that the metabolic complications associated with the obesity model were not fully established, probably due to the age at the start of the protocol (11 weeks), individual housing and short duration of the exposure to the high-fat feed. This fact may have prevented the observation of the positive effects of D-limonene in reversing parameters that would normally be impaired by the development of obesity. We conclude that D-limonene may interfere in energy metabolism, with a possible anti-obesogenic and anti-inflammatory effect. Due to the limitations of the model, further studies are needed to confirm these findings
Subject(s)Animals , Male , Mice , Limonene/adverse effects , Obesity/chemically induced , In Vitro Techniques/methods , Chronic Disease/classification , Citrus sinensis/metabolism , Monoterpenes/analysis , Diet, High-Fat/adverse effects , Inflammation/complications , Anti-Inflammatory Agents/administration & dosage
Abstract The study was aimed to assess impact of high fat diet (HFD) and synthetic human gut microbiota (GM) combined with HFD and chow diet (CD) in inducing type-2 diabetes (T2D) using mice model. To our knowledge, this is the first study using selected human GM transplantation via culture based method coupled dietary modulation in mice for in vivo establishment of inflammation leading to T2D and gut dysbiosis. Twenty bacteria (T2D1-T2D20) from stool samples of confirmed T2D subjects were found to be morphologically different and subjected to purification on different media both aerobically and anerobically, which revealed seven bacteria more common among 20 isolates on the basis of biochemical characterization. On the basis of 16S rRNA gene sequencing, these seven isolates were identified as Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenes (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). The seven isolates were subsequently used as synthetic gut microbiome (GM) for their role in inducing T2D in mice. Inbred strains of albino mice were divided into four groups and were fed with CD, HFD, GM+HFD and GM+CD. Mice receiving HFD and GM+modified diet (CD/HFD) showed highly significant (P<0.05) increase in weight and blood glucose concentration as well as elevated level of inflammatory cytokines (TNF-α, IL-6, and MCP-1) compared to mice receiving CD only. The 16S rRNA gene sequencing of 11 fecal bacteria obtained from three randomly selected animals from each group revealed gut dysbiosis in animals receiving GM. Bacterial strains including Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) and Lactobacillus gasseri (MT152635) were isolated from mice treated with GM+modified diet (HFD/CD) compared to strains Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629) which were isolated from mice receiving CD/HFD. In conclusion, these findings suggest that constitution of GM and diet plays significant role in inflammation leading to onset or/and possibly progression of T2D. .
Resumo O estudo teve como objetivo avaliar o impacto da dieta rica em gordura (HFD) e da microbiota intestinal humana sintética (GM) combinada com HFD e dieta alimentar (CD) na indução de diabetes tipo 2 (T2D) usando modelo de camundongos. Para nosso conhecimento, este é o primeiro estudo usando transplante de GM humano selecionado através do método baseado em cultura acoplada à modulação dietética em camundongos para o estabelecimento in vivo de inflamação que leva a T2D e disbiose intestinal. Vinte bactérias (T2D1-T2D20) de amostras de fezes de indivíduos T2D confirmados verificaram ser morfologicamente diferentes e foram submetidas à purificação em meios diferentes aerobicamente e anaerobicamente, o que revelou sete bactérias mais comuns entre 20 isolados com base na caracterização bioquímica. Com base no sequenciamento do gene 16S rRNA, esses sete isolados foram identificados como Bacteroides stercoris (MT152636), Lactobacillus acidophilus (MT152637), Lactobacillus salivarius (MT152638), Ruminococcus bromii (MT152639), Klebsiella aerogenides (MT152640), Bacteroides fragilis (MT152909), Clostridium botulinum (MT152910). Esses sete isolados foram, posteriormente, usados como microbioma intestinal sintético (GM) por seu papel na indução de T2D em camundongos. Linhagens consanguíneas de camundongos albinos foram divididas em quatro grupos e foram alimentadas com CD, HFD, GM + HFD e GM + CD. Camundongos que receberam a dieta modificada com HFD e GM + (CD / HFD) mostraram um aumento altamente significativo (P < 0,05) no peso e na concentração de glicose no sangue, bem como um nível elevado de citocinas inflamatórias (TNF-α, IL-6 e MCP-1) em comparação com os ratos que receberam apenas CD. O sequenciamento do gene 16S rRNA de 11 bactérias fecais obtidas de três animais selecionados aleatoriamente de cada grupo revelou disbiose intestinal em animais que receberam GM. Cepas bacterianas, incluindo Bacteroides gallinarum (MT152630), Ruminococcus bromii (MT152631), Lactobacillus acidophilus (MT152632), Parabacteroides gordonii (MT152633), Prevotella copri (MT152634) e Lactobacillus Gasseri (MT152635D), foram tratadas com dieta modificada / CD) em comparação com as linhagens Akkermansia muciniphila (MT152625), Bacteriodes sp. (MT152626), Bacteroides faecis (MT152627), Bacteroides vulgatus (MT152628), Lactobacillus plantarum (MT152629), que foram isoladas de camundongos recebendo CD / HFD. Em conclusão, esses resultados sugerem que a constituição de GM e dieta desempenham papel significativo na inflamação levando ao início ou/e possivelmente à progressão de T2D.
Subject(s)Humans , Animals , Rabbits , Diabetes Mellitus, Type 2 , Gastrointestinal Microbiome , Bacteroides , RNA, Ribosomal, 16S/genetics , Prevotella , Bacteroidetes , Ruminococcus , Diet, High-Fat/adverse effects , Dysbiosis , Inflammation , Mice, Inbred C57BL
Abstract Consuming a high-fat diet causes a harmful accumulation of fat in the liver, which may not reverse even after switching to a healthier diet. Different reports dealt with the role of purslane as an extract against high-fat diet; meanwhile, it was necessary to study the potential role of fresh purslane as a hypolipidemic agent. This study is supposed to investigate further the potential mechanism in the hypolipidemic effect of fresh purslane, by measuring cholesterol 7a-hydroxylase (CYP7A1) and low-density lipoprotein receptor (Ldlr). Rats were divided into two main groups: the first one is the normal control group (n=7 rats) and the second group (n=28 rats) received a high fat diet for 28 weeks to induce obesity. Then the high fat diet group was divided into equal four subgroups. As, the positive control group still fed on a high fat diet only. Meanwhile, the other three groups were received high-fat diet supplemented with a different percent of fresh purslane (25, 50 and 75%) respectively. At the end of the experiment, rats were sacrificed and samples were collected for molecular, biochemical, and histological studies. Current study reported that, supplementation of fresh purslane especially at a concentration of 75% play an important role against harmful effects of high-fat diet at both cellular and organ level, by increasing CYP7A1 as well as Ldlr mRNA expression. Also, there were an improvement on the tested liver functions, thyroid hormones, and lipid profile. Fresh purslane plays the potential role as a hypolipidemic agent via modulation of both Ldlr and Cyp7A, which will point to use fresh purslane against harmful effects of obesity.
Resumo O consumo de uma dieta rica em gordura causa um acúmulo prejudicial de gordura no fígado, que pode não reverter mesmo após a mudança para uma dieta mais saudável. Diferentes relatórios trataram do papel da beldroega como um extrato contra uma dieta rica em gordura; entretanto, foi necessário estudar o papel potencial da beldroega fresca como agente hipolipemiante. Este estudo pretende investigar mais profundamente o mecanismo potencial no efeito hipolipidêmico da beldroega fresca, medindo o colesterol 7a-hidroxilase (CYP7A1) e o receptor de lipoproteína de baixa densidade (Ldlr). Os ratos foram divididos em dois grupos principais: o primeiro é o grupo controle normal (n = 7 ratos) e o segundo grupo (n = 28 ratos) recebeu dieta rica em gorduras por 28 semanas para induzir a obesidade. Em seguida, o grupo de dieta rica em gordura foi dividido em quatro subgrupos iguais. Como, o grupo de controle positivo ainda se alimentava apenas com dieta rica em gordura. Enquanto isso, os outros três grupos receberam dieta rica em gordura suplementada com diferentes porcentagens de beldroegas frescas (25%, 50% e 75%), respectivamente. Ao final do experimento, os ratos foram sacrificados e amostras coletadas para estudos moleculares, bioquímica e histológicos. O estudo atual relatou que a suplementação de beldroegas frescas, especialmente a uma concentração de 75%, desempenha papel importante contra os efeitos prejudiciais da dieta rica em gordura em nível celular e orgânico, aumentando a expressão de CYP7A1 e Ldlr mRNA. Além disso, houve melhora nas funções hepáticas testadas, nos hormônios tireoidianos e no perfil lipídico. Beldroegas frescas desempenham papel potencial como agente hipolipemiante por meio da modulação de Ldlr e Cyp7A, o que apontará para o uso de beldroegas frescas contra os efeitos nocivos da obesidade.
Subject(s)Animals , Rats , Portulaca , Diet, High-Fat/adverse effects , Hypolipidemic Agents , Cholesterol 7-alpha-Hydroxylase , Rats, Sprague-Dawley , Liver
The inverse relationship between HDL-C (high-density lipoprotein cholesterol) and cardiovascular disease is well established. However, it is consensus that the cholesterol content present in HDL does not capture its complexity, and other metrics need to be explored. HDL is a heterogeneous, protein-enriched particle with functions going beyond lipid metabolism. In this way, its protein content seems to be attractive to investigate its behavior in the face of pathologies. Many of the proteins with important function in HDL are in low abundance (<1% of total proteins), which makes their detection challenging. Quantitative proteomics allows detecting proteins with high precision and robustness in complex matrix. However, quantitative proteomics is still poorly explored in the context of HDL. In this sense, in the second chapter of this thesis, the analytical performance of two quantitative methodologies was carefully investigated. These methods achieved adequate linearity and high precision using labeled peptides in a pool HDL, in addition to comparable ability to differentiate proteins from HDL subclasses of healthy subjects. Another bottleneck that waits for a solution in proteomics is the lack of standardization in data processing and analysis after mass spectrometry acquisition. In addition, interest in the cardioprotective properties of omega-3 is growing, but little is known about its effects on the HDL proteome. Thus, in the third chapter of this thesis, we compared five protein quantification strategies using Skyline and MaxDIA software platforms in order to investigate the HDL proteome from mice submitted to a high-fat diet supplemented or not with omega-3. MaxDIA with label-free quantification (MaxLFQ) achieved high precision to show that polyunsaturated fatty acids remodel the HDL proteome to a less inflammatory profile. Therefore, the two studies presented in this thesis begin to open new paths for a deeper and more reliable understanding of HDL, both at the level of protein quantification by mass spectrometry and after data acquisition
A inversa relação entre HDL-C (do inglês, high-density lipoprotein cholesterol) e doenças cardiovasculares é bem estabelecida. No entanto, é consenso que o conteúdo de colesterol presente na HDL não captura sua complexidade, e outras métricas precisam ser exploradas. A HDL é uma partícula heterogênea, enriquecida em proteínas, com funções que vão além do metabolismo de lipídeos. Dessa forma, seu conteúdo proteico parece ser mais atrativo para exprimir seu comportamento frente às patologias. Muitas das proteínas com função importante estão em baixa abundância (<1% do total de proteínas), o que torna a detecção desafiadora. Métodos quantitativos de proteômica permitem detectar proteínas com alta precisão e robustez em matrizes complexas. No entanto, a proteômica quantitativa ainda é pouco explorada no contexto da HDL. Nesse sentido, no segundo capítulo dessa tese, a performance analítica de dois métodos quantitativos foi criteriosamente investigada, os quais alcançaram adequada linearidade e alta precisão usando peptídeos marcados em um pool de HDL, além de comparável habilidade em diferenciar as proteínas das subclasses da HDL de indivíduos saudáveis. Outro gargalo que aguarda por solução em proteômica é a falta de padronização no processamento e análise de dados após a aquisição por espectrometria de massas. Além disso, é crescente o interesse das propriedades cardioprotetivas do ômega-3, porém pouco se conhece sobre seus efeitos no proteoma da HDL. Então, no terceiro capítulo dessa tese, comparamos cinco estratégias de quantificação de proteínas utilizando os softwares Skyline e MaxDIA com o intuito de comparar o proteoma da HDL de camundongos submetidos a uma dieta hiperlipídica suplementados ou não com ômega-3. MaxDIA com quantificação label-free (MaxLFQ) apresentou alta precisão para mostrar que o ômega-3 remodela o proteoma da HDL para um perfil menos inflamatório. Portanto, os dois estudos apresentados nessa tesa começam a abrir novos caminhos para o entendimento mais profundo e confiável da HDL tanto por meio da quantificação das proteínas por espectrometria de massas quanto após à aquisição dos dados
Subject(s)Proteomics/instrumentation , Hyperlipidemias/pathology , Cholesterol, HDL/analysis , Mass Spectrometry/methods , Cardiovascular Diseases/pathology , Diet/classification , Diet, High-Fat/adverse effects
OBJECTIVE@#This study aimed to investigate the effects of caprylic acid (C8:0) on lipid metabolism and inflammation, and examine the mechanisms underlying these effects in mice and cells.@*METHODS@#Fifty-six 6-week-old male C57BL/6J mice were randomly allocated to four groups fed a high-fat diet (HFD) without or with 2% C8:0, palmitic acid (C16:0) or eicosapentaenoic acid (EPA). RAW246.7 cells were randomly divided into five groups: normal, lipopolysaccharide (LPS), LPS+C8:0, LPS+EPA and LPS+cAMP. The serum lipid profiles, inflammatory biomolecules, and ABCA1 and JAK2/STAT3 mRNA and protein expression were measured.@*RESULTS@#C8:0 decreased TC and LDL-C, and increased the HDL-C/LDL-C ratio after injection of LPS. Without LPS, it decreased TC in mice ( P < 0.05). Moreover, C8:0 decreased the inflammatory response after LPS treatment in both mice and cells ( P < 0.05). Mechanistic investigations in C57BL/6J mouse aortas after injection of LPS indicated that C8:0 resulted in higher ABCA1 and JAK2/STAT3 expression than that with HFD, C16:0 and EPA, and resulted in lower TNF-α, NF-κB mRNA expression than that with HFD ( P < 0.05). In RAW 264.7 cells, C8:0 resulted in lower expression of pNF-κBP65 than that in the LPS group, and higher protein expression of ABCA1, p-JAK2 and p-STAT3 than that in the LPS and LPS+cAMP groups ( P < 0.05).@*CONCLUSION@#Our studies demonstrated that C8:0 may play an important role in lipid metabolism and the inflammatory response, and the mechanism may be associated with ABCA1 and the p-JAK2/p-STAT3 signaling pathway.
Subject(s)Animals , Humans , Male , Mice , ATP Binding Cassette Transporter 1/immunology , Caprylates/chemistry , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Inflammation/metabolism , Janus Kinase 2/immunology , Lipid Metabolism/drug effects , Macrophages/immunology , Mice, Inbred C57BL , STAT3 Transcription Factor/immunology , Signal Transduction
Mounting evidence has shown that exercise exerts extensive beneficial effects, including preventing and protecting against chronic diseases, through improving metabolism and other mechanisms. Recent studies have shown that exercise preconditioning affords significant cardioprotective effects. However, whether exercise preconditioning improves high fat diet (HFD)-induced obesity and lipid metabolic disorder remains unknown. The study was aimed to explore the effects of exercise preconditioning on HFD-induced obesity and lipid metabolic disorder in mice. 4-week-old C57BL/6 mice were subjected to swimming or sedentary control for 3 months, and then were fed with normal diet (ND) or HFD for 4 more months. The results showed that the blood glucose was decreased, and the glucose tolerance and grip strength were increased in exercised mice after training. Exercise preconditioning failed to improve HFD-induced body weight gain, but improved HFD-induced glucose intolerance. Exercise preconditioning showed no significant effects on both exercise capacity and physical activity in ND- and HFD-fed mice. HFD feeding increased total cholesterol and low density lipoprotein (LDL) levels in circulation, promoted subcutaneous fat and epididymal fat accumulation in mice. Exercise preconditioning increased circulating high density lipoprotein (HDL) and decreased circulating LDL, without affecting the subcutaneous fat and epididymal fat in HFD-fed mice. HFD feeding increased liver weight and hepatic total cholesterol contents, and dysregulated the expressions of several mitochondria function-related proteins in mice. These abnormalities were partially reversed by exercise preconditioning. Together, these results suggest that exercise preconditioning can partially reverse the HFD-induced lipid metabolic disorder and hepatic dysfunction, and these beneficial effects of exercise sustain for a period of time, even after exercise is discontinued.
Subject(s)Animals , Mice , Cholesterol/metabolism , Diet, High-Fat/adverse effects , Lipids , Liver , Mice, Inbred C57BL , Obesity
Exposure to the hight-fat diet may alter the control of food intake promoting hyperphagia and obesity. The objective of this study was to investigate the effects of this diet on dopamine receptors (drd1 and drd2), proopiomelanocortin (pomc), neuropeptideY (npy) genes expression, and preference food in adult rats. Wistar female rats were fed a hight-fat or control diet during pregnancy and lactation. The offspring were allocated into groups: Lactation - Control (C) and High-fat (H). Post-weaning Control Control (CC), offspring of mothers C, fed a control diet after weaning; Control Hight-fat (CH), offspring of mothers C, fed a hight-fat diet after weaning; Hight-fat Control (HC), offspring of mothers H, fed with control diet after weaning; and Hight-fat Hight-fat (HH), offspring of mothers H, fed a H diet after weaning. The groups CH and HH presented greater expression of drd1 in comparison to the CC. The drd2 of CH and HC presented higher gene expression than did CC. HH presented higher pomc expression in comparison to the other groups. HC also presented greater expression in comparison to CH. The npy of HH presented greater expression in relation to CH and HC. HH and HC have had a higher preference for a high-fat diet at 102º life's day. The high-fat diet altered the gene expression of the drd1, drd2, pomc and npy, and influencing the food preference for high-fat diet.
A exposição à dieta hiperlipídica pode alterar o controle da ingestão de alimentos, promovendo hiperfagia e obesidade. O objetivo deste estudo foi investigar os efeitos dessa dieta sobre a expressão gênica dos receptores de dopamina (drd1 e drd2), da proopiomelanocortina (pomc) e neuropeptídeo Y (npy), e preferência alimentar em ratos adultos. Ratas Wistar foram alimentadas com uma dieta hiperlipídica ou controle durante a gestação e lactação. Os descendentes foram alocados em grupos: Lactação Controle (C) e Hiperlipídica (H). Pós-desmame - Controle Controle (CC), descendentes das genitoras do grupo controle e alimentados com dieta controle após o desmame; Controle Hiperlipídica (CH), descendentes das genitoras do grupo controle e alimentados com dieta hiperlipídica após o desmame; Hiperlipídica Controle (HC), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta controle após o desmame; Hiperlipídica Hiperlipídica (HH), descendentes das genitoras do grupo hiperlipídica e alimentados com dieta hiperlipídica após o desmame. Os grupos CH e HH apresentaram maior expressão de drd1 em comparação ao CC. O drd2 de CH e HC apresentou maior expressão gênica que o CC. HH apresentou maior expressão de pomc em comparação com os outros grupos. O HC também apresentou maior expressão de pomc em comparação ao CH. O npy do HH apresentou maior expressão em relação ao CH e HC. HH e HC tiveram uma preferência maior por uma dieta rica em gordura no 102º dia de vida. A dieta hiperlipídica alterou a expressão gênica dos drd1, drd2, pomc e npy e influenciou na preferência alimentar pela dieta hiperlipídica.
Subject(s)Animals , Female , Pregnancy , Rats , Pro-Opiomelanocortin/genetics , Diet, High-Fat/adverse effects , Body Weight , Neuropeptide Y/genetics , Gene Expression , Receptors, Dopamine/genetics , Rats, Wistar , Food Preferences
The current investigation was carried out to estimate the protective effect of aqueous extract of Cheatomorpha gracilis (AEC) against High fat Diet (HFD) induced liver damage in mice. The results of the in vitro study showed that AEC have higher antioxidant capacities in the DPPH and hydroxyl radical-scavenging assays. Indeed, many phenolic compounds (gallic acid, quercetin, naringenin, apigenin, kaempferol and rutin) were identified in the AEC. In the animal studies, during 6 weeks, HFD promoted oxidative stress with a rise level of malonaldehyde (MDA), protein carbonyls (PCOs) levels and a significant decrease of the antioxidant enzyme activities such as superoxide dismutase, catalase and glutathione peroxidase. Interestingly, the treatment with AEC (250 mg/kg body weight) significantly reduced the effects of HFD disorders on some plasmatic liver biomarkers (AST, ALT and ALP) in addition to, plasmatic proteins inflammatory biomarkers (α2 and ß1 decreases / ß2 and Î³ globulins increases). It can be suggest that supplementation of MECG displays high potential to quench free radicals and attenuates high fat diet promoted liver oxidative stress and related disturbances.
A presente investigação foi realizada para estimar o efeito protetor do extrato aquoso de Cheatomorpha gracilis (AEC) contra o dano hepático induzido por dieta rica em gordura (HFD) em camundongos. Os resultados do estudo in vitro mostraram que os AEC têm maiores capacidades antioxidantes nos ensaios DPPH e de eliminação de radicais hidroxila. De fato, muitos compostos fenólicos (ácido gálico, quercetina, naringenina, apigenina, kaempferol e rutina) foram identificados no AEC. Nos estudos em animais, durante 6 semanas, HFD promoveu estresse oxidativo com aumento do nível de malonaldeído (MDA), níveis de proteína carbonil (PCOs) e diminuição significativa das atividades de enzimas antioxidantes como superóxido dismutase, catalase e glutationa peroxidase. Curiosamente, o tratamento com AEC (250 mg / kg de peso corporal) reduziu significativamente os efeitos dos distúrbios de HFD em alguns biomarcadores hepáticos plasmáticos (AST, ALT e ALP), além de biomarcadores inflamatórios de proteínas plasmáticas (reduções α2 e ß1 / ß2 e Î³ aumenta as globulinas). Pode-se sugerir que a suplementação de MECG apresenta alto potencial para extinguir os radicais livres e atenua o estresse oxidativo do fígado promovido pela dieta rica em gordura e distúrbios relacionados.
Subject(s)Animals , Rats , Plant Extracts/pharmacology , Diet, High-Fat/adverse effects , Chromatography, High Pressure Liquid , Oxidative Stress , Liver , Antioxidants/metabolism
This study aimed to explore the effects of Gynostemma pentaphyllum saponins(GPs) on non-alcoholic fatty liver disease(NAFLD) induced by high-fat diet in rats and reveal the underlying mechanism. The NAFLD model rats were prepared with high-fat diet. Forty male Sprague Dawley(SD) rats were randomly assigned into the control group, model group, and low-, moderate-, and high-dose GPs(50, 100, and 150 mg·kg~(-1), respectively) groups. After intragastric administration for 8 continuous weeks, we determined the body weight, liver weight, the levels of total cholesterol(TC), triglyceride(TG), low-density lipoprotein cholesterol(LDL-c), high-density lipoprotein cholesterol(HDL-c), alanine aminotransferase(ALT), and aspartate aminotransferase(AST) in serum, and the levels of TC, TG, malondialdehyde(MDA), superoxide dismutase(SOD), catalase(CAT), and interleukin 6(IL-6) in the liver. Furthermore, we observed the pathological changes of liver tissue by oil red O staining and hematoxylin-eosin(HE) staining, sequenced the 16 S rRNA of the intestinal flora in rat feces, and determined the content of short-chain fatty acids in rat feces. The results showed that GPs inhibited the excessive weight gain of high-fat diet-induced NAFLD in rats, reduced the liver weight, lowered the TC, TG, LDL-c, AST, and ALT levels in serum(P<0.05), and rose the HDL-c level in serum(P<0.01). GPs relieved the liver damage caused by high-fat diet, mainly manifested by the lowered levels of TC, TG, MDA, and IL-6 in the liver(P<0.01) and elevated levels of CAT and SOD in the liver. Furthermore, GPs reversed the intestinal flora disorder caused by high-fat diet, restored the diversity of intestinal flora, increased the relative abundance of Bacteroides, and reduced the relative abundance of Firmicutes and the ratio of Firmicutes to Bacteroides. Moreover, GPs promoted the proliferation of beneficial bacteria such as Akkermansia, Bacteroides, and Parabacteroides, and inhibited the growth of harmful bacteria such as Desulfovibrio, Escherichia-Shigella, and Helicobacter. GPs increased the content of short-chain fatty acids(acetic acid, propionic acid, and butyric acid)(P<0.01). These findings indicate that GPs can alleviate the high-fat diet-induced NAFLD in rats via regulating the intestinal flora and short-chain fatty acid metabolism.
Subject(s)Animals , Male , Rats , Alanine Transaminase/metabolism , Cholesterol, LDL/pharmacology , Diet, High-Fat/adverse effects , Gastrointestinal Microbiome , Gynostemma , Interleukin-6/metabolism , Liver , Non-alcoholic Fatty Liver Disease/metabolism , Rats, Sprague-Dawley , Saponins/pharmacology , Superoxide Dismutase/metabolism
Objective: To investigate the effects of continuous exercise training (CT) and high-intensity interval exercise training (HIIT) on liver lipid metabolism and the correlation of the level of fibroblast growth factor 21(FGF21) in serum and liver tissues. Methods: Male SD rats were randomly divided into normal diet group (N) and obesity model group (H) after 1 week of adaptive feeding. Rats in the obesity model group were fed with 45% high-fat diet for about 8 weeks, and 20% weight increase compared with normal rats was considered as obesity. The rats were divided into normal diet control group (LC), normal diet HIIT group (LHI), normal diet CT group (LCT), High fat diet-induced obese control group (OC), obese HIIT group (OHI), and obese CT group (OCT) (n=10). Exercised rats were given weight-bearing swimming training intervention for 8 weeks. Blood samples were collected at least 24h after the last exercise intervention to detect the serum levels of inflammatory factors and FGF21. Liver tissue samples were collected to detect the lipid content, lipid metabolic enzyme content and FGF21 expression level. Results: Compared with LC group, the body weight, serum inflammatory factors levels and hepatic triglyceride content were increased significantly (P＜0.05). Hepatic triglyceride content was downregulated in LHI group and FGF21 expression level was enhanced in LCT group (P＜0.05). Compared with OC group, the body weight and hepatic triglyceride content were decreased significantly (P＜0.05), mitochondrial CPT-1β and β-HAD enzyme contents in liver were increased significantly (P＜0.05) in OHI group, the contents of LPL and FAT/CD36 enzyme in liver and the levels of FGF21 in serum and liver of OCT group were increased significantly (P＜0.05). Conclusion: Both exercise modes can reduce the body weight in normal and obese rats, and lipid deposition in the liver of obese rats. HIIT has a more significant effect on alleviating liver lipid deposition in obese rats by upregulating mitochondrial lipid oxidation level in normal and obese rats. CT improves the levels of FGF21 in serum and liver tissues of normal and obese rats, enhances enzyme contents that involved in fatty acids uptake to the liver, which has limited effect on alleviating lipid deposition in liver of obese rats.
Subject(s)Animals , Male , Rats , Body Weight , Diet, High-Fat/adverse effects , Fatty Liver , Fibroblast Growth Factors , Obesity/metabolism , Rats, Sprague-Dawley , Triglycerides
OBJECTIVE@#To investigate the changes of tetraspanin 8 (TSPAN8) expression levels and its role in lipid metabolism during the development of non-alcoholic fatty liver disease (NAFLD).@*METHODS@#Thirty male C57BL/6J mice were randomly divided into normal diet group and high-fat diet (HFD) group (n=15), and after feeding for 1, 3, and 6 months, the expression levels of TSPAN8 in the liver tissues of the mice were detected with Western blotting. In a HepG2 cell model of NAFLD induced by free fatty acids (FFA), the effect of TSPAN8 overexpression on lipid accumulation was examined using Oil Red O staining and an automated biochemical analyzer, and the mRNA expressions of the key genes involved in lipid metabolism were detected using qRT-PCR.@*RESULTS@#Western blotting showed that compared with that in mice with normal feeding, the expression of TSPAN8 was significantly decreased in the liver tissues of mice with HFD feeding for 3 and 6 months (P < 0.05). In HepG2 cells, treatment with FFA significantly decreased the expression of TSPAN8 at both the mRNA and protein levels (P < 0.01). TSPAN8 overexpression in FFA-treated cells showed significantly lowered intracellular triglyceride levels (P < 0.001) and obviously reduced mRNA expression of fatty acid transport protein 5 (FATP5) (P < 0.01). The expression of FATP5 was significantly increased in FFA-treated cells as compared with the control cells (P < 0.001).@*CONCLUSION@#TSPAN8 is involved in lipid metabolism in NAFLD, and overexpression of TSPAN8 may inhibit cellular lipid deposition by reducing the expression of FATP5.
Subject(s)Animals , Male , Mice , Diet, High-Fat/adverse effects , Fatty Acids, Nonesterified , Lipid Metabolism , Liver/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/metabolism , RNA, Messenger/metabolism
Abstract Introduction: Obesity, diabetes, and hypertension are common risk factors for chronic kidney disease (CKD). CKD arises due to many pathological insults, including inflammation and oxidative stress, which affect renal function and destroy nephrons. Rice bran (RB) is rich in vitamins and minerals, and contains signiﬁcant amount of antioxidants. The aim of this study was to evaluate the preventive effect of RB on renal disease risk factors. Methods: Male Wistar rats (±325 g) were divided into two experimental groups to received a high sugar-fat diet (HSF, n = 8) or high sugar-fat diet with rice bran (HSF + RB, n = 8) for 20 weeks. At the end, renal function, body composition, metabolic parameters, renal inflammatory and oxidative stress markers were analyzed. Results: RB prevented obesity [AI (HSF= 9.92 ± 1.19 vs HSF + RB= 6.62 ± 0.78)], insulin resistance [HOMA (HSF= 83 ± 8 vs. HSF + RB= 42 ± 11)], dyslipidemia [TG (HSF= 167 ± 41 vs. HSF + RB=92 ± 40)], inflammation [TNF-α (HSF= 80 ± 12 vs. HSF + RB=57 ± 14), IL-6 (903 ± 274 vs. HSF + RB=535 ± 277)], oxidative stress [protein carbonylation (HSF= 3.38 ± 0.18 vs. HSF + RB=2.68 ± 0.29), RAGE (HSF=702 ± 36 vs. RSF + RB=570 ± 190)], and renal disease [protein/creatinine ratio (HSF=1.10 ± 0.38 vs. HSF + RB=0.49 ± 0.16)]. Conclusion: In conclusion, rice bran prevented renal disease by modulating risk factors.
Resumo Introdução: Obesidade, diabetes e hipertensão arterial são fatores de risco comuns para doenças renais crônicas (DRC). A DRC surge devido a muitos insultos patológicos, incluindo inflamação e estresse oxidativo, que afetam a função renal e destroem os néfrons. O farelo de arroz (FA) é rico em vitaminas e minerais, e contém uma quantidade significativa de antioxidantes. O objetivo deste estudo foi avaliar o efeito preventivo do FA nos fatores de risco de doenças renais. Métodos: Ratos Wistar machos (±325 g) foram divididos em dois grupos experimentais para receber uma dieta rica em gordura e açúcar (DRGA, n = 8) ou uma dieta rica em gordura e açúcar com farelo de arroz (DRGA + FA, n = 8) por 20 semanas. Ao final, foram analisados a função renal, composição corporal, parâmetros metabólicos, marcadores renais inflamatórios e de estresse oxidativo. Resultados: FA preveniu a obesidade [IA (DRGA= 9,92 ± 1,19 vs. DRGA + FA= 6,62 ± 0. 78)], resistência à insulina [HOMA (DRGA= 83 ± 8 vs DRGA + FA= 42 ± 11)], dislipidemia [TG (DRGA= 167 ± 41 vs. DRGA + FA=92 ± 40)], inflamação [FNT-α (DRGA= 80 ± 12 vs. DRGA + FA=57 ± 14), IL-6 (903 ± 274 vs. DRGA + FA= 535 ± 277)], estresse oxidativo [carbonilação de proteína (DRGA= 3. 38 ± 0,18 vs. DRGA + FA=2,68 ± 0,29), RAGE (DRGA=702 ± 36 vs. DRGA + FA=570 ± 190)], e doença renal [relação proteína/creatinina (DRGA=1,10 ± 0,38 vs. DRGA + FA=0,49 ± 0,16)]. Conclusão: Em conclusão, o farelo de arroz preveniu doenças renais através da modulação dos fatores de risco.
Subject(s)Animals , Male , Rats , Oryza , Risk Factors , Rats, Wistar , Oxidative Stress , Sugars , Diet, High-Fat/adverse effects , Kidney/physiology
ABSTRACT Objective: Obesity is characterized by a state of chronic, low-intensity systemic inflammation frequently associated with insulin resistance and dyslipidemia. Materials and methods: Given that chronic inflammation has been implicated in the pathogenesis of mood disorders, we investigated if chronic obesity that was initiated early in life - lasting through adulthood - could be more harmful to memory impairment and mood fluctuations such as depression. Results: Here we show that pre-pubertal male rats (30 days old) treated with a high-fat diet (40%) for 8-months gained ~50% more weight when compared to controls, exhibited depression and anxiety-like behaviors but no memory impairment. The prefrontal cortex of the obese rats exhibited an increase in the expression of genes related to inflammatory response, such as NFKb, MMP9, CCl2, PPARb, and PPARg. There were no alterations in genes known to be related to depression. Conclusion: Long-lasting obesity with onset in prepuberal age led to depression and neuroinflammation but not to memory impairment.
Subject(s)Animals , Male , Rats , Behavior, Animal , Depression/etiology , Anxiety , Diet, High-Fat/adverse effects , Obesity
Nonalcoholic fatty liver disease (NAFLD), characterized by hepatosteatosis and steatohepatitis, is intrinsically related to obesity. Our previous study reported on the anti-obese activity of α,β-amyrin (AMY), a pentacyclic triterpene isolated from Protium heptaphyllum. This study investigated its ability to prevent fatty liver and the underlying mechanism using the mouse model of NAFLD. NAFLD was induced in male Swiss mice fed a high fat diet (HFD) for 15 weeks. The controls were fed a normal chow diet (ND). The mice were simultaneously treated with AMY at 10 and 20 mg/kg or fenofibrate at 50 mg/kg. Lipid levels along with metabolic and inflammatory parameters were assessed in liver and serum. The liver sections were histologically examined using H&E staining. RT-qPCR and western blotting assays were performed to analyze signaling mechanisms. Mice fed HFD developed severe hepatic steatosis with elevated triglycerides and lipid droplets compared with ND controls. This was associated with a decrease in AMP-activated protein kinase (AMPK) activity, an increase of mechanistic target of rapamycin complex 1 (mTORC1) signaling, and enhanced sterol regulatory element binding protein 1 (SREBP1) expression, which have roles in lipogenesis, inhibition of lipolysis, and inflammatory response. AMY treatment reversed these signaling activities and decreased the severity of hepatic steatosis and inflammatory response, evidenced by serum and liver parameters as well as histological findings. AMY-induced reduction in hepatic steatosis seemed to involve AMPK-mTORC1-SREBP1 signaling pathways, which supported its beneficial role in the prevention and treatment of NAFLD.
Subject(s)Animals , Male , Rabbits , Insulin Resistance , Non-alcoholic Fatty Liver Disease/prevention & control , Non-alcoholic Fatty Liver Disease/drug therapy , Oleanolic Acid/analogs & derivatives , Sterol Regulatory Element Binding Protein 1 , AMP-Activated Protein Kinases , Diet, High-Fat/adverse effects , Mechanistic Target of Rapamycin Complex 1 , Liver , Mice, Inbred C57BL
Mechanisms involved in cardiac function and calcium (Ca2+) handling in obese-resistant (OR) rats are still poorly determined. We tested the hypothesis that unsaturated high-fat diet (HFD) promotes myocardial dysfunction in OR rats, which it is related to Ca2+ handling. In addition, we questioned whether exercise training (ET) becomes a therapeutic strategy. Male Wistar rats (n=80) were randomized to standard or HFD diets for 20 weeks. The rats were redistributed for the absence or presence of ET and OR: control (C; n=12), control + ET (CET; n=14), obese-resistant (OR; n=9), and obese-resistant + ET (ORET; n=10). Trained rats were subjected to aerobic training protocol with progressive intensity (55-70% of the maximum running speed) and duration (15 to 60 min/day) for 12 weeks. Nutritional, metabolic, and cardiovascular parameters were determined. Cardiac function and Ca2+ handling tests were performed in isolated left ventricle (LV) papillary muscle. OR rats showed cardiac atrophy with reduced collagen levels, but there was myocardial dysfunction. ET was efficient in improving most parameters of body composition. However, the mechanical properties and Ca2+ handling from isolated papillary muscle were similar among groups. Aerobic ET does not promote morphological and cardiac functional adaptation under the condition of OR.
Subject(s)Animals , Male , Rats , Physical Conditioning, Animal , Obesity , Rats, Wistar , Diet, High-Fat/adverse effects , Heart
ABSTRACT Purpose: To evaluate the morphological, biochemical, and histological effects of aqueous extracts of peanut (skinless and added to 1% skin) in Swiss mice submitted to a high-fat diet. Methods: Forty male Swiss mice were divided into four groups (n=10 per group): GI) normocaloric diet; GII) high-fat diet; GIII) high-fat diet + 0.5 mL of peanut extract; GIV) high-fat diet + 0.5 mL of peanut extract + 1% peanut skin. The animals were weighed weekly and euthanized after 12 weeks for histopathological and biochemical analyses. The study was approved by the Animal Use Ethics Committee. Results: The animals in the GIV group had higher body weight when compared to the other ones. Increase in total cholesterol in GIII, increase in blood glucose in groups GII, GIII and GIV, decrease in serum low-density lipoprotein (LDL) concentration in groups GI and GIV and increase in serum concentration of C-reactive protein in GII were seen. The presence of vacuolar fat deposits was found in animal livers from GII. Conclusions: The extracts improved the plasma concentrations of animals that received a high-fat diet, including preventing morphological damage to liver tissue. These benefits were enhanced by the association of peanut shells with the extract.
Subject(s)Arachis , Diet, High-Fat/adverse effects , Plant Extracts/pharmacology , Overweight , Liver
OBJECTIVES@#To study the effect of high-fat diet for maternal Sprague-Dawley rats at different stages on glucose and lipid metabolism in offspring and related mechanisms.@*METHODS@#According to the diet before pregnancy and during pregnancy and lactation, maternal rats were randomly divided into four groups (@*RESULTS@#Compared with the control diet groups (CC and CH groups), the groups with high-fat diet before pregnancy (HC and HH groups) had a significant increase in body weight (@*CONCLUSIONS@#High-fat diet for rats at different stages before and after pregnancy has different effects on glucose and lipid metabolism of offspring rats, and high-fat diet before pregnancy and during pregnancy and lactation has the greatest effect. The effect of high-fat diet on glucose and lipid metabolism of offspring rats is considered associated with the changes in the expression of genes involved in glucose and lipid metabolism.
Subject(s)Animals , Female , Male , Pregnancy , Rats , Body Weight , Diet, High-Fat/adverse effects , Glucose/metabolism , Insulin , Insulin Resistance , Lipid Metabolism , Liver/metabolism , Rats, Sprague-Dawley
This study investigated the differential mechanisms of Rehmanniae Radix and Rehmanniae Radix Praeparata in improving diabetes in mice through AMPK-mediated NF-κB/NLRP3 signaling pathway. The diabetic mouse model was established with high-fat diet coupled with streptozotocin(STZ, intraperitoneal injection, 100 mg·kg~(-1), once a day for three consecutive days), after which the mice were randomly divided into model group, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix groups, low-dose(5 g·kg~(-1)) and high-dose(15 g·kg~(-1)) Rehmanniae Radix Praeparata groups, catalpol group(250 mg·kg~(-1)), 5-hydroxymethylfurfural(5-HMF) group(250 mg·kg~(-1)), metformin group(250 mg·kg~(-1)), with the normal group also set. The organ indexes of heart,liver, spleen, lung, kidney and pancreas were calculated after four weeks of administration. The pathological changes and fibrosis of pancreas, kidney and liver in mice were observed by hematoxylin-eosin(HE) staining and Masson staining. Western blot was used to determine the expression levels of Toll-like receptor-4(TLR4), nuclear factor-κB(NF-κB), Nod-like receptor protein 3(NLRP3),interleukin-1β(IL-1β), adenosine monophosphate-activated protein kinase(AMPK), phosphorylated AMPK(p-AMPK) in the pancreas, kidney and liver of mice. Compared with the model group, the administration groups witnessed significant decrease in the liver,spleen, kidney, pancreas and fat indexes of diabetic mice, and there was no significant difference in heart and lung indexes. The pathological states and fibrosis of pancreatic, kidney and liver tissues were significantly improved after administration. Additionally, the expression levels of TLR4, NF-κB and NLRP3 in pancreas, kidney and liver of diabetic mice were significantly lowered. The expression levels of p-AMPK/AMPK were enhanced significantly in kidney and liver of mice in Rehmanniae Radix group while in pancreas, kidney and liver in Rehmanniae Radix Praeparata group. This suggests that Rehmanniae Radix and Rehmanniae Radix Praeparata differ in the mechanism of regulating energy metabolism of multiple organs and thereby exerting anti-inflammatory effects to alleviate symptoms of diabetic mice.
Subject(s)Animals , Mice , AMP-Activated Protein Kinases/genetics , Diabetes Mellitus, Experimental/drug therapy , Diet, High-Fat/adverse effects , NF-kappa B/metabolism , NLR Family, Pyrin Domain-Containing 3 Protein , Plant Extracts , Rehmannia , Signal Transduction , Streptozocin
This study aimed to investigate the effects and the underlying mechanism of CD36 gene on glucose and lipid metabolism disorder induced by high-fat diet in mice. Wild type (WT) mice and systemic CD36 knockout (CD36
Subject(s)Animals , Mice , Diet, High-Fat/adverse effects , Fatty Liver/metabolism , Glucose/metabolism , Insulin/metabolism , Insulin Resistance , Lipid Metabolism , Liver , Triglycerides
OBJECTIVE@#To study the effects of buckwheat-oat-pea (BOP) composite flour [buckwheat ∶ oats ∶ peas=6 ∶ 1 ∶ 1 (quality ratio)] on blood glucose in diabetic rats.@*METHODS@#In this study, 64 male Sprague-Dawley rats were divided into 8 groups by fasting blood glucose (FBG) and body weight: normal control group, model control group, metformin group, buckwheat group, oats group, BOP low-dose group (BOP-L), medium-dose group (BOP-M), and high-dose group (BOP-H). The rats in the normal control group were fed with normal diet, the rats in the model control group and metformin group were fed with a high-fat diet (HFD), and the rats in the buckwheat group, oats group, and BOP-L, BOP-M, BOP-H groups were fed with HFD containing 10% buckwheat flour, 10% oat flour, 3.3% BOP, 10% BOP, 30% BOP, respectively. The HFD in all the groups had the same percentage of energy from fat (45%). After 30 days, the rats fed with HFD received intraperitoneal injection of streptozotocin (30 mg/kg, once a week for two weeks) to establish diabetes mellitus. After the model was successful established, the rats were fed for another 28 days. During the study, the body weight, food intake/body weight (FI/BW) and water intake/body weight (WI/BW), food utilization rate, 24 h urine volume, FBG, glucose area under curve (GAUC) of oral glucose tolerance test were measured regularly. At the end of the study, the fasting serum glucose and insulin were measured, and homeostasis model assessment of insulin resistance (HOMA-IR) was calculated.@*RESULTS@#With the inducing of HFD and streptozotocin, compared with the normal control group, the rats in the model control group had higher FI/BW, WI/BW, 24 h urine volume, FBG, GAUC, HOMA-IR (P < 0.05), and lower body weight, food utilization rate (P < 0.05). Compared with the model control group, the rats in the three BOP groups all had higher body weight, food utilization rate (P < 0.05), and lower WI/BW, HOMA-IR (P < 0.05); the rats in the BOP-L and BOP-M groups had lower FI/BW, 24 h urine volume, FBG (P < 0.05), and the rats in the BOP-M group also had lower GAUC (P < 0.05). After the establishment of diabetes, there was no significant difference in blood glucose and the other indicators between the rats in the three BOP groups and the buckwheat group or the oats group (P>0.05).@*CONCLUSION@#The BOP had the effects of reducing blood glucose, insulin resistance and diabetic symptoms on diabetic rats, and had the value for further development and utilization.