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1.
J Nutr Sci Vitaminol (Tokyo) ; 67(5): 283-291, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34719613

RESUMO

Zeolite, an abundant mineral in the Earth's crust, is utilized in a wide range of fields because of its well-known adsorption properties. Its application as a functional food ingredient resembling dietary fiber is expected, but it has not yet been investigated in the context of prevention of lifestyle-related diseases. The present study was designed to evaluate the availability and safety of a natural zeolite preparation for this purpose. Acute oral toxicity testing showed that the lowest lethal dose of zeolite was more than 2,000 mg/kg body weight for both male and female mice. In a prolonged feeding test for 18 wk using model mice with high-fat-induced obesity and type 2 diabetes mellitus, intake of a 10% zeolite-containing diet suppressed body weight gain, as well as liver and visceral fat weights, without any changes in food and energy intake. Moreover, plasma lipid (triacylglycerol, total cholesterol and high-density-lipoprotein cholesterol) levels and fasting blood glucose levels decreased in parallel with zeolite intake. No changes in the glycated hemoglobin level were found. However, in an oral glucose tolerance test at week 12, increased postprandial blood glucose levels were suppressed in accordance with zeolite intake, and then insulin secretion was also decreased. On the other hand, a decrease of plasma amylase activity and increases in total bilirubin and urea nitrogen suggested the need for further investigation of safety.


Assuntos
Diabetes Mellitus Tipo 2 , Hiperglicemia , Hiperlipidemias , Zeolitas , Animais , Glicemia , Diabetes Mellitus Tipo 2/prevenção & controle , Dieta Hiperlipídica/efeitos adversos , Feminino , Hiperlipidemias/etiologia , Hiperlipidemias/prevenção & controle , Insulina , Masculino , Camundongos , Obesidade/etiologia , Obesidade/prevenção & controle
2.
Nat Commun ; 12(1): 5323, 2021 09 07.
Artigo em Inglês | MEDLINE | ID: mdl-34493722

RESUMO

The role of intestine clock in energy homeostasis remains elusive. Here we show that mice with Bmal1 specifically deleted in the intestine (Bmal1iKO mice) have a normal phenotype on a chow diet. However, on a high-fat diet (HFD), Bmal1iKO mice are protected against development of obesity and related abnormalities such as hyperlipidemia and fatty livers. These metabolic phenotypes are attributed to impaired lipid resynthesis in the intestine and reduced fat secretion. Consistently, wild-type mice fed a HFD during nighttime (with a lower BMAL1 expression) show alleviated obesity compared to mice fed ad libitum. Mechanistic studies uncover that BMAL1 transactivates the Dgat2 gene (encoding the triacylglycerol synthesis enzyme DGAT2) via direct binding to an E-box in the promoter, thereby promoting dietary fat absorption. Supporting these findings, intestinal deficiency of Rev-erbα, a known BMAL1 repressor, enhances dietary fat absorption and exacerbates HFD-induced obesity and comorbidities. Moreover, small-molecule targeting of REV-ERBα/BMAL1 by SR9009 ameliorates HFD-induced obesity in mice. Altogether, intestine clock functions as an accelerator in dietary fat absorption and targeting intestinal BMAL1 may be a promising approach for management of metabolic diseases induced by excess fat intake.


Assuntos
Fatores de Transcrição ARNTL/genética , Ritmo Circadiano/genética , Diacilglicerol O-Aciltransferase/genética , Fígado Gorduroso/genética , Hiperlipidemias/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética , Obesidade/genética , Fatores de Transcrição ARNTL/deficiência , Animais , Diacilglicerol O-Aciltransferase/metabolismo , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/administração & dosagem , Gorduras na Dieta/metabolismo , Fígado Gorduroso/etiologia , Fígado Gorduroso/metabolismo , Fígado Gorduroso/prevenção & controle , Regulação da Expressão Gênica , Homeostase/efeitos dos fármacos , Homeostase/genética , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/prevenção & controle , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Metabolismo dos Lipídeos/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/antagonistas & inibidores , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/metabolismo , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/prevenção & controle , Regiões Promotoras Genéticas , Ligação Proteica , Pirrolidinas/farmacologia , Transdução de Sinais , Tiofenos/farmacologia , Triglicerídeos/biossíntese
3.
BMJ Open ; 11(7): e048590, 2021 07 05.
Artigo em Inglês | MEDLINE | ID: mdl-34226229

RESUMO

OBJECTIVE: The objective of this study was to evaluate the influence of secondhand smoke (SHS) exposure during childhood on type 2 diabetes mellitus, hypertension, hyperlipidaemia and coronary heart disease among Chinese non-smoking women. METHODS: In this cross-sectional study, the SHS exposure data in childhood were obtained using a questionnaire survey. Self-reported childhood SHS exposure was defined as the presence of at least one parent who smoked during childhood. RESULTS: Of the 6522 eligible participants, 2120 Chinese women who had never smoked were assessed. The prevalence of SHS exposure in the entire population was 28.1% (596). SHS exposure during childhood was not significant for the standard risk factors of type 2 diabetes mellitus (p=0.628) and hypertension (p=0.691). However, SHS was positively associated with hyperlipidaemia (p=0.037) after adjusting for age, obesity, education status, physical activity, alcohol consumption, current SHS exposure status, diabetes mellitus and hypertension. In addition, childhood SHS increased the occurrence of coronary heart disease (p=0.045) among non-smokers after further adjusting for hyperlipidaemia. CONCLUSION: SHS exposure during childhood is associated with prevalent hyperlipidaemia and coronary heart disease in adulthood among non-smoking Chinese women.


Assuntos
Doença das Coronárias , Diabetes Mellitus Tipo 2 , Hiperlipidemias , Poluição por Fumaça de Tabaco , Adulto , China/epidemiologia , Doença das Coronárias/epidemiologia , Doença das Coronárias/etiologia , Estudos Transversais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/etiologia , Exposição Ambiental/efeitos adversos , Feminino , Humanos , Hiperlipidemias/epidemiologia , Hiperlipidemias/etiologia , Inquéritos e Questionários , Poluição por Fumaça de Tabaco/efeitos adversos
4.
Chem Biol Interact ; 347: 109601, 2021 Sep 25.
Artigo em Inglês | MEDLINE | ID: mdl-34324854

RESUMO

Exploration of long-term in vivo effects of nanomaterials, particularly those with potential biomedical applications, is quite important for better understanding and evaluating their biosafety. Selenium nanoparticles (SeNPs) has been considered as a good candidate in biomedical applications due to its high bioavailability, considerable biological activity, and low toxicity. However, its long-term biological effects and biosafety remain unknown. Our previous study demonstrated that 8-week supplementation with SeNPs (50 µg Se/kg/day) was safe and had an anti-atherosclerotic activity in apolipoprotein E-deficient (ApoE-/-) mice, a well-known animal model of atherosclerosis. As a chronic disease, atherosclerosis needs long-term drug therapy. The aim of this study is to investigate the long-term effects of SeNPs with different sizes on atherosclerotic lesions and their biosafety in ApoE-/- mice fed with a high fat diet. Unexpectedly, the results showed that 24-week administration of SeNPs even at a low dose (50 µg Se/kg/day) aggravated atherosclerotic lesions. Furthermore, SeNPs exacerbated oxidative stress by inhibiting the activities of antioxidant enzymes and the expression of antioxidant selenoenzymes. SeNPs also exacerbated hyperlipidaemia by inducing hepatic lipid metabolic disorder. In the meanwhile, SeNPs aggravated organ injury, especially liver and kidney injury. The above adverse effects of SeNPs were size dependent: SeNPs with the size of 40.4 nm showed the highest adverse effects among the SeNPs with three sizes (23.1 nm, 40.4 nm, and 86.8 nm). In conclusion, the present work shows that long-term administration of low-dose SeNPs aggravated atherosclerotic lesions by enhancing oxidative stress and hyperlipidaemia in ApoE-/- mice, indicative of cardiovascular toxicity. Moreover, long-term administration of SeNPs led to injury to liver and kidney. These results offer novel insights for better understanding the biosafety of SeNPs and other biomedical nanomaterials.


Assuntos
Aterosclerose/etiologia , Nanopartículas/toxicidade , Selênio/toxicidade , Animais , Apolipoproteínas E/deficiência , Aterosclerose/metabolismo , Aterosclerose/patologia , Doença Hepática Induzida por Substâncias e Drogas/etiologia , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Doença Hepática Induzida por Substâncias e Drogas/patologia , Glutationa Peroxidase/metabolismo , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Nefropatias/etiologia , Nefropatias/metabolismo , Nefropatias/patologia , Fígado/patologia , Efeitos Adversos de Longa Duração , Masculino , Camundongos , Nanopartículas/administração & dosagem , Nanopartículas/química , Estresse Oxidativo/efeitos dos fármacos , Tamanho da Partícula , Selênio/administração & dosagem , Selênio/química , Tiorredoxina Redutase 1/metabolismo , Tiorredoxina Redutase 2/metabolismo
5.
Molecules ; 26(14)2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-34299566

RESUMO

Citrus fruits are a rich source of high-value bioactive compounds and their consumption has been associated with beneficial effects on human health. Red (blood) oranges (Citrus sinensis L. Osbeck) are particularly rich in anthocyanins (95% of which are represented by cyanidin-3-glucoside and cyanidin-3-6″-malonyl-glucoside), flavanones (hesperidin, narirutin, and didymin), and hydroxycinnamic acids (caffeic acid, coumaric acid, sinapic, and ferulic acid). Lemon fruit (Citrus limon) is also rich in flavanones (eriocitrin, hesperidin, and diosmin) and other polyphenols. All of these compounds are believed to play a very important role as dietary antioxidants due to their ability to scavenge free radicals. A standardized powder extract, red orange and lemon extract (RLE), was obtained by properly mixing anthocyanins and other polyphenols recovered from red orange processing waste with eriocitrin and other flavanones recovered from lemon peel by a patented extraction process. RLE was used for in vivo assays aimed at testing a potential beneficial effect on glucose and lipid metabolism. In vivo experiments performed on male CD1 mice fed with a high-fat diet showed that an 8-week treatment with RLE was able to induce a significant reduction in glucose, cholesterol and triglycerides levels in the blood, with positive effects on regulation of hyperglycemia and lipid metabolism, thus suggesting a potential use of this new phytoextract for nutraceutical purposes.


Assuntos
Citrus , Hiperglicemia/tratamento farmacológico , Hiperlipidemias/tratamento farmacológico , Hipoglicemiantes/uso terapêutico , Hipolipemiantes/uso terapêutico , Extratos Vegetais/uso terapêutico , Animais , Antocianinas/química , Antocianinas/uso terapêutico , Antioxidantes/química , Antioxidantes/uso terapêutico , Citrus/química , Dieta Hiperlipídica/efeitos adversos , Flavanonas/química , Flavanonas/uso terapêutico , Hiperglicemia/etiologia , Hiperlipidemias/etiologia , Hipoglicemiantes/química , Hipolipemiantes/química , Masculino , Camundongos , Extratos Vegetais/química
6.
J Agric Food Chem ; 69(27): 7629-7640, 2021 Jul 14.
Artigo em Inglês | MEDLINE | ID: mdl-34213907

RESUMO

A high-fat diet (HFD) causes hyperlipidemia, which worsens disturbances in bile acid (BA) metabolism and gut microbiota. This study aimed to investigate the regulation of flavonoids from whole-grain oat (FO) on BA metabolism and gut microbiota in HFD-induced hyperlipidemic mice. The experiment results showed that FO improved serum lipid profiles and decreased body weight and lipid deposition in HFD-fed mice. Through real-time qualitative polymerase chain reaction (RT-qPCR) and Western blot assays, by up-regulating the expression of PPARα, CPT-1, CYP7A1, FXR, TGR5, NTCP, and BSTP, and down-regulating those of SREBP-1c, FAS, and ASBT, FO suppressed lipogenesis, promoted lipolysis and BA synthesis, and efflux to faeces via the FXR pathway. 16s rRNA sequencing revealed that FO significantly increased Akkermansia and significantly decreased Lachnoclostridium, Blautia, Colidextribacter, and Desulfovibrio. Spearman's correlation analysis showed that these bacteria were strongly correlated with hyperlipidemia-related parameters. Therefore, our results indicated that FO possessed an antihyperlipidemic effect via regulating the gut-liver axis, i.e., BA metabolism and gut microbiota.


Assuntos
Microbioma Gastrointestinal , Hiperlipidemias , Animais , Avena , Ácidos e Sais Biliares , Dieta Hiperlipídica/efeitos adversos , Flavonoides , Hiperlipidemias/etiologia , Hiperlipidemias/genética , Metabolismo dos Lipídeos , Camundongos , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S
7.
Nutrients ; 13(7)2021 Jun 29.
Artigo em Inglês | MEDLINE | ID: mdl-34209561

RESUMO

Obesity is one of the major health problems worldwide. Following healthy dietary patterns can be difficult in some countries due to the lack of availability of certain foods; thus, alternative foods are needed. Our aim was to evaluate the effect of a dietary pattern consisting of fruit, avocado, whole grains, and trout (FAWGT) on postprandial insulinemia and lipemia in obese Colombian subjects. A randomized controlled crossover study was conducted, in which 44 subjects with BMI ≥ 30 kg/m2 followed either a FAWGT diet or a diet high in saturated fat and rich in processed carbohydrates. Levels of lipids and carbohydrates were measured during the postprandial state. The FAWGT diet reduced fasting insulin, VLDL, and HOMA-IR after 8 weeks (p < 0.05), while there was a lower postprandial increase in TG, VLDL, and insulin levels after both acute and chronic intake of FAWGT diet (p < 0.05). The intake of FAWGT-diet was characterized by high consumption of foods rich in fiber, MUFAs, and vitamins C and E (p < 0.05). The consumption of a diet composed of fruit, avocado, whole grains, and trout has emerged as a valid alternative to the foods included in other heart-healthy diets since it improves postprandial lipemia and insulinemia in obese people and has similar beneficial effects to these healthy models.


Assuntos
Dieta Saudável/métodos , Ingestão de Alimentos/fisiologia , Hiperinsulinismo/dietoterapia , Hiperlipidemias/dietoterapia , Obesidade/dietoterapia , Animais , Glicemia/análise , Índice de Massa Corporal , VLDL-Colesterol/sangue , Estudos Cross-Over , Carboidratos da Dieta/administração & dosagem , Gorduras na Dieta/administração & dosagem , Jejum/sangue , Feminino , Frutas , Humanos , Hiperinsulinismo/sangue , Hiperinsulinismo/etiologia , Hiperlipidemias/sangue , Hiperlipidemias/etiologia , Insulina/sangue , Resistência à Insulina , Lipídeos/sangue , Masculino , Pessoa de Meia-Idade , Obesidade/sangue , Obesidade/complicações , Persea , Período Pós-Prandial/fisiologia , Alimentos Marinhos , Triglicerídeos/sangue , Truta , Grãos Integrais
8.
Sci Rep ; 11(1): 12478, 2021 06 14.
Artigo em Inglês | MEDLINE | ID: mdl-34127697

RESUMO

Childhood eating behaviour contributes to the rise of obesity and related noncommunicable disease worldwide. However, we lack a deep understanding of biochemical alterations that can arise from aberrant eating behaviour. In this study, we prospectively associate longitudinal trajectories of childhood overeating, undereating, and fussy eating with metabolic markers at age 16 years to explore adolescent metabolic alterations related to specific eating patterns in the first 10 years of life. Data are from the Avon Longitudinal Study of Parents and Children (n = 3104). We measure 158 metabolic markers with a high-throughput (1H) NMR metabolomics platform. Increasing childhood overeating is prospectively associated with an adverse cardiometabolic profile (i.e., hyperlipidemia, hypercholesterolemia, hyperlipoproteinemia) in adolescence; whereas undereating and fussy eating are associated with lower concentrations of the amino acids glutamine and valine, suggesting a potential lack of micronutrients. Here, we show associations between early behavioural indicators of eating and metabolic markers.


Assuntos
Doenças Cardiovasculares/epidemiologia , Fenômenos Fisiológicos da Nutrição Infantil , Comportamento Alimentar , Hiperlipidemias/epidemiologia , Hiperfagia/complicações , Adolescente , Índice de Massa Corporal , Fatores de Risco Cardiometabólico , Doenças Cardiovasculares/diagnóstico , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/metabolismo , Criança , Comportamento Infantil , Pré-Escolar , Feminino , Humanos , Hiperlipidemias/diagnóstico , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperfagia/epidemiologia , Hiperfagia/metabolismo , Hiperfagia/psicologia , Lactente , Recém-Nascido , Estudos Longitudinais , Masculino , Metabolômica , Estudos Prospectivos , Inquéritos e Questionários/estatística & dados numéricos
9.
Sci Rep ; 11(1): 9931, 2021 05 11.
Artigo em Inglês | MEDLINE | ID: mdl-33976292

RESUMO

Whether anthropometric or body composition indices are better indicators of metabolic risk remains unclear. The objectives of this study were to compare the association of metabolic risk factors with anthropometric and body composition indices and to identify the better indicators for risk factors in a large-scale Korean population. In this cross-sectional study, the associations of body mass index (BMI), waist circumference (WC), and waist-to-height ratio (WHtR) as anthropometric indices and trunk fat mass (TFM), percent trunk fat mass (%TFM), whole-body total fat mass (WBTFM), and percent whole-body total fat mass (%WBTFM) as body composition indices with metabolic risk factors were compared by complex-samples multiple logistic regression models based on complex-sample survey data. In men, WHtR, BMI, and TFM were similarly associated with hypertension. Diabetes, hyperlipidemia, and hypo-high-density lipoprotein (HDL) cholesterolemia tended to be more strongly associated with WHtR and WC than body composition indices. Hypertriglyceridemia and hypercholesterolemia were more strongly associated with WHtR and %TFM than other indices. In women, hypertension tended to be more strongly associated with WHtR than other indices. TFM, %TFM, and WHtR were similarly associated with hyperlipidemia. Diabetes and hypo-HDL cholesterolemia were more strongly associated with WHtR and WC than body composition indices. Hypertriglyceridemia and hypercholesterolemia were more strongly associated with WHtR and %TFM than other indices. Among six metabolic risk factors, the validity and utility of the anthropometric indices in identifying risk factors tended to be similar to or better than those of the body composition indices, except for hypertension and hypercholesterolemia in men and hyperlipidemia and hypercholesterolemia in women.


Assuntos
Diabetes Mellitus/etiologia , Hiperlipidemias/etiologia , Hipertensão/etiologia , Adulto , Composição Corporal , Índice de Massa Corporal , Estudos Transversais , Diabetes Mellitus/metabolismo , Feminino , Humanos , Hiperlipidemias/metabolismo , Hipertensão/metabolismo , Masculino , Fatores de Risco , Circunferência da Cintura , Razão Cintura-Estatura
10.
Mol Nutr Food Res ; 65(6): e2001090, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33559369

RESUMO

SCOPE: This study aimed to explore the anti-obesity potential of blackcurrant anthocyanins (BCA) and investigate the correlation between the gut microbiota and the BCA-induced beneficial effects. METHODS AND RESULTS: Male C57BL/6J mice (n = 36) are randomly assigned into low-fat diet group (LFD), high-fat diet group (HFD), and BCA group feeding HFD supplemented with BCA for 12 weeks. Body weight and food intake are monitored weekly. Obesity-related biochemical indexes and the expression levels of genes related to lipid metabolism are determined. Amplicon sequencing of the bacterial 16S rRNA gene is conducted to analyze the gut microbiota structure, and spearman correlation analysis is used to determine the correlations between gut microbiota and obesity-related indicators. The results showed that BCA treatment alleviated HFD-induced obesity, hyperlipemia, and hepatic steatosis. Moreover, BCA supplement improved hepatic lipid metabolism by regulating the expression of genes related to the synthesis and degradation of lipids and cholesterols. Microbial analysis revealed that BCA supplementation significantly changed the overall structure and composition of the gut microbiota, and resulted in an enrichment of Akkermansia_muciniphila, which is negatively correlated with the physical biomarkers. CONCLUSION: This study demonstrated that BCA supplement could be a beneficial treatment for preventing HFD-induced obesity by targeting microbiota.


Assuntos
Antocianinas/farmacologia , Microbioma Gastrointestinal/efeitos dos fármacos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/dietoterapia , Ribes/química , Animais , Dieta Hiperlipídica , Microbioma Gastrointestinal/fisiologia , Hiperlipidemias/dietoterapia , Hiperlipidemias/etiologia , Metabolismo dos Lipídeos/genética , Masculino , Camundongos Endogâmicos C57BL , Camundongos Obesos , Hepatopatia Gordurosa não Alcoólica/dietoterapia , Hepatopatia Gordurosa não Alcoólica/etiologia , Hepatopatia Gordurosa não Alcoólica/patologia , Obesidade/etiologia , Obesidade/metabolismo , Obesidade/microbiologia , Transcriptoma/efeitos dos fármacos
11.
Nutr Hosp ; 38(2): 281-289, 2021 Apr 19.
Artigo em Inglês | MEDLINE | ID: mdl-33478227

RESUMO

Introduction: Background: the dietary pattern that characterizes western diet is strongly associated with metabolic diseases and excess weight, as well as chronic illnesses. Misaligned feeding schedules can lead to or aggravate the development of such conditions. Aim: this study evaluated the influence of dietary composition and/or time-restricted feeding on the anthropometric and biochemical profile of adult rats. Methods: forty male rats, at 60 days of life, were divided into the following groups: Control (C), Restricted Control (RC), Westernized (W), and Restricted Westernized (RW). Results: westernized groups, in spite of a low energy intake (C = 5399 ± 401.2 kcal; RC = 4279.0 ± 476.2 kcal; W = 4302 ± 619.8 kcal; RW = 4081.0 ± 404.4 kcal, p < 0.001), had a higher body weight (C = 404.6 ± 39.1 g; RC = 335.1 ± 36.5 g; W = 488.9 ± 51.2 g; RW = 438.8 ± 36.5 g, p < 0.001) as compared to their paired controls (RC and C) - around 30 % and 20 % more for RW and W, respectively. The westernized diet caused glucose intolerance and mixed hyperlipidemia, characterized by higher concentrations of cholesterol (C = 40.8 ± 7.4 mg/dL; RC = 76.7 ± 10.8 mg/dL; W = 61.3 ± 20.2 mg/dL; RW = 42.2 ± 8.2 mg/dL), LDLc (C = 17.4 ± 7.5 mg/dL; RC = 38.8 ± 7.2 mg/dL ; W = 45.3 ± 15.8 mg/dL; RW = 11.0 ± 5.8 mg/dL), and triacylglycerol (C = 45.2 ± 15.0 mg/dL; RC = 73.2 ± 21.5 mg/dL ; W = 83.6 ± 23.4 mg/dL; RW = 57.5 ± 13.6 mg/dL) in the serum (p < 0.05). Conclusion: the effect of time-restricted feeding on body weight was strongly dependent on diet composition. The glucose tolerance test showed an influence of the circadian cycle phase. Mixed hyperlipidemia varied according to the presence of westernized diet and/or time-restricted food.


Assuntos
Ritmo Circadiano , Dieta Ocidental/efeitos adversos , Jejum/efeitos adversos , Hiperlipidemias/etiologia , Animais , Glicemia/metabolismo , Colesterol/sangue , Escuridão , Ingestão de Energia , Intolerância à Glucose/etiologia , Teste de Tolerância a Glucose , Hiperlipidemias/sangue , Masculino , Ratos , Ratos Wistar , Triglicerídeos/sangue , Ganho de Peso
12.
Free Radic Biol Med ; 165: 229-242, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33513420

RESUMO

Ferroptosis is a form of regulated cell death that involves metabolic dysfunction resulting from iron-dependent excessive lipid peroxidation. Elevated plasma levels of free fatty acids are tightly associated with cardiometabolic risk factors in patients with obesity, diabetes mellitus, and metabolic syndrome. Metformin (Met) is an antidiabetic drug with beneficial cardiovascular disease effects. The aim of this study was to determine the effects of Met on ferroptosis induced by lipid overload and the effects of these changes on vascular smooth muscle cells (VSMCs) calcification. We developed a hyperlipidaemia-related vascular calcification in vivo model with rats fed a high-fat diet combined with vitamin D3 plus nicotine, and palmitic acid (PA), the most abundant long-chain saturated fatty acid in plasma, was used to induce lipid overload and develop an oxidative stress-related calcification model in vitro. The results showed that Met inhibits hyperlipidaemia-associated calcium deposition in the rat aortic tissue. In vitro, treatment of VSMCs with PA stimulates ferroptosis concomitant with increased calcium deposition in VSMCs, while pretreatment with Met attenuates these effects. Furthermore, PA also promotes the protein expression of the extracellular matrix protein periostin (POSTN) and its secretion into the extracellular environment. More importantly, upregulation of POSTN increased the sensitivity of cells to ferroptosis. Mechanistically, upregulation of POSTN suppresses SLC7A11 expression through the inhibition of p53 in VSMCs, which contributes to a decrease in glutathione synthesis and therefore triggers ferroptosis. Interestingly, overexpression of p53 attenuates the inhibitory effect of POSTN on SLC7A11 expression, accompanied by increased Gpx4 expression. Furthermore, p53 knockdown suppresses Met-mediated anti-ferroptosis effects in PA-treated VSMCs, which may be related to the downregulation of SLC7A11 expression. In addition, supplementation of VSMCs with Met enhances the antioxidative capacity of VSMCs through Nrf2 signalling activation. Collectively, targeting POSTN in VSMCs may provide a new strategy for vascular calcification prevention or treatment.


Assuntos
Hiperlipidemias , Metformina , Calcificação Vascular , Animais , Humanos , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/etiologia , Metformina/farmacologia , Músculo Liso Vascular , Miócitos de Músculo Liso , Ratos , Calcificação Vascular/tratamento farmacológico , Calcificação Vascular/etiologia
13.
J Pharmacol Exp Ther ; 377(1): 146-156, 2021 04.
Artigo em Inglês | MEDLINE | ID: mdl-33509902

RESUMO

Insulin resistance (IR) is the common basis of diabetes and cardiovascular diseases, and its development is closely associated with lipid metabolism disorder. Flavonoids have definite chemical defense effects, including anti-inflammatory effects, anticancer effects, and antimutation effects. However, the function and mechanism of apigenin (AP, a kind of flavonoid) in IR are still unclear. In our study, intracellular fat accumulation model cells and high-fat diet (HFD)-fed model mice were established using palmitate (PA) and HFD. Mechanistically, we first demonstrated that AP could notably downregulate sterol regulatory element-binding protein 1c (SREBP-1c), sterol regulatory element-binding protein 2 (SREBP-2), fatty acid synthase, stearyl-CoA desaturase 1, and 3-hydroxy-3-methyl-glutaryl-CoA reductase in PA-induced hyperlipidemic cells and mice. Functionally, we verified that AP could markedly reduce lipid accumulation in PA-induced hyperlipidemic cells and decrease the body weight, visceral fat weight, IR, and lipid accumulation in HFD-induced hyperlipidemic mice. Besides, we showed that PA could significantly downregulate endoplasmic reticulum stress (ERS)-related proteins and inhibit ERS. Furthermore, we proved that AP could reduce blood lipids by inhibiting ERS in PA-induced hyperlipidemic cells. Meanwhile, 4-phenyl butyric acid (also called ERS alleviator), like AP, could significantly reduce blood lipids and alleviate IR in HFD-fed model mice. Therefore, we concluded that AP could substantially improve the disorder of lipid metabolism, and its mechanism might be related to the decrease of SREBP-1c, SREBP-2, and downstream genes, the inhibition of ERS, and the reduction of blood lipids and IR. SIGNIFICANCE STATEMENT: Apigenin, a nontoxic and naturally sourced flavonoid, has antihyperlipidemic properties in mice and hepatocyte. This study highlights a new mechanism of apigenin and proposes that these hypolipidemic effects are associated with the mitigation of endoplasmic reticulum stress and insulin resistance in diet-induced obesity. This study might provide translational insight into the prevention and treatment of apigenin in hyperlipidemia-related diseases.


Assuntos
Apigenina/farmacologia , Estresse do Retículo Endoplasmático , Hiperlipidemias/tratamento farmacológico , Hipolipemiantes/farmacologia , Resistência à Insulina , Metabolismo dos Lipídeos , Adiposidade/efeitos dos fármacos , Animais , Apigenina/uso terapêutico , Dieta Hiperlipídica/efeitos adversos , Células Hep G2 , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hipolipemiantes/uso terapêutico , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Palmitatos/farmacologia , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 2/metabolismo
14.
J Sci Food Agric ; 101(6): 2561-2569, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-33063356

RESUMO

BACKGROUND: Hyperlipidemia is one of the metabolic disorders that poses a great threat to human health. This study is aimed at investigating the potential hypolipidemic properties of extract from peanut meal fermented with Bacillus natto and Monascus in mice fed with a high-fat diet. Herein, 60 male C57BL/6J mice were randomly divided into six groups: four control groups, comprised of a normal group, a model (M) group, a positive control group (atorvastatin 10 mg kg-1 ), and a nonfermented peanut meal extract group (150 mg kg-1 ), and two experimental groups, comprised of a fermented peanut meal extract low-dose group (50 mg kg-1 ) and a fermented peanut meal extract high-dose group (FH, 150 mg kg-1 ). RESULTS: Body weight (P = 0.001) and levels of serum total cholesterol (P = 0.007), triacylglycerol (P = 0.040), low-density lipoprotein cholesterol (P < 0.001), and leptin (P < 0.001) were remarkably decreased in the FH group, whereas the serum high-density lipoprotein cholesterol levels were increased (P < 0.001) by 78.3% compared with the M group. Ileum tissue stained with hematoxylin and eosin showed that the ileal villus detachments in mice were improved, and the villus height was increased by supplementation with extract from fermented peanut meal. Moreover, the expressions of intestinal ZO-1 (P = 0.003) and occludin (P = 0.013) were elevated in the FH group, compared with the M group. CONCLUSION: Extract of peanut meal fermented by B. natto and Monascus can effectively improve hyperlipidemia caused by a high-fat diet in mice, via regulating leptin and blood lipid levels, and protect the intestinal mucosal barrier, which provides evidence for its anti-hyperlipidemia effects and is a research basis for potential industrial development. © 2020 Society of Chemical Industry.


Assuntos
Arachis/metabolismo , Bacillus/metabolismo , Hiperlipidemias/dietoterapia , Hipolipemiantes/metabolismo , Metabolismo dos Lipídeos , Monascus/metabolismo , Extratos Vegetais/metabolismo , Animais , Arachis/microbiologia , HDL-Colesterol , LDL-Colesterol , Dieta Hiperlipídica/efeitos adversos , Fermentação , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Mucosa Intestinal/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Alimentos de Soja/análise , Alimentos de Soja/microbiologia , Triglicerídeos/metabolismo
15.
Clin Nutr ; 40(2): 420-427, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-32684486

RESUMO

BACKGROUND & AIMS: Postprandial lipaemic response has emerged as a risk factor for cardiovascular disease. Dietary fats such as medium-chain saturated fatty acids (MCSFA) and long-chain omega-3 polyunsaturated fatty acids (LCn-3PUFA) are known to reduce postprandial lipaemic responses. The combination of the two could potentially have complementary and/or synergistic effects for optimising cardiovascular health. This study aims to investigate the effects of MCSFA (coconut oil) with or without LCn-3PUFA (fish oil) inclusion in the test meal on postprandial blood lipids in healthy adults. METHODS: In a randomised, double-blinded, placebo-controlled, 2 × 2 factorial cross-over study, participants (n = 15) were randomised to receive four standardised isocaloric test meals. Test meals include: placebo [PL, containing no fish oil (0 g EPA & DHA) or coconut oil (0 g MCSFA)], fish oil [FO, 6 g fish oil (3.85 g EPA & DHA), containing no coconut oil (0 g MCSFA)], coconut oil [CO, 18.65 g coconut oil (15 g MCSFA), containing no fish oil (0 g EPA & DHA)] and coconut oil + fish oil [COFO, 18.65 g coconut oil (15 g MCSFA) + 6 g fish oil (3.85 g EPA & DHA)]; all providing a total fat content of 33.5 g. Participants received all four treatments on four separate test days with at least 3 days washout in between. Blood parameters were measured by finger pricks at 7 timepoints between 0 and 300min. The primary outcome of this study was the change in postprandial triglycerides (TG) concentrations with secondary outcomes as total cholesterol, high-density lipoprotein cholesterol and blood glucose concentrations. RESULTS: TG area under the curve (AUC) (mmol/L/min) was significantly lower for FO (383.67, p = 0.0125) and COFO (299.12, p = 0.0186) in comparison to PL (409.17) only. TG incremental area under the curve (iAUC) (mmol/L/min) was significantly lower with COFO (59.67) in comparison to CO (99.86), (p = 0.0480). Compared to PL, the change in absolute TG concentrations (mmol/L) from baseline to post TG peak time (180min) after FO were significantly less at 240min (0.39 vs 0.15), 270min (0.2 vs 0.1), and 300min (0.28 vs 0.06), and after COFO was significantly less at 300min (0.28 vs 0.16) (p < 0.05). No significant differences in postprandial AUC and iAUC for any other blood parameters were reported. CONCLUSIONS: Our study demonstrated that LCn-3PUFA with or without MCSFA but not MCSFA alone are effective in reducing postprandial TG in healthy individuals.


Assuntos
Gorduras na Dieta/administração & dosagem , Ácidos Graxos Ômega-3/administração & dosagem , Hiperlipidemias/prevenção & controle , Refeições/fisiologia , Período Pós-Prandial/efeitos dos fármacos , Adulto , Idoso , Glicemia/metabolismo , Colesterol/sangue , Óleo de Coco/administração & dosagem , Estudos Cross-Over , Método Duplo-Cego , Feminino , Óleos de Peixe/administração & dosagem , Alimentos Fortificados , Voluntários Saudáveis , Humanos , Hiperlipidemias/etiologia , Lipoproteínas HDL/sangue , Masculino , Pessoa de Meia-Idade , Triglicerídeos/sangue
16.
J Microbiol Biotechnol ; 31(2): 181-188, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33144552

RESUMO

Bacillus subtilis and Enterococcus faecium are commonly used probiotics. This study aimed to identify the effect of live combined Bacillus subtilis R0179 and Enterococcus faecium R0026 (LCBE) on obesityassociated hyperlipidemia and gut microbiota in C57BL/6 mice. Forty male C57BL/6 mice were divided into four groups: normal group (N group), model group (M group), low-dose group (L group), and high-dose group (H group). Mice were gavaged with LCBE at 0.023 g/mice/day (L group) or 0.23 g/mice/day (H group) and fed with a high-fat diet for 8 weeks. In vitro E. faecium R0026 showed an ability to lower the low-concentration of cholesterol by 46%, and the ability to lower the highconcentration of cholesterol by 58%. LCBE significantly reduced the body weight gain, Lee index, brown fat index and body mass index of mice on a high-fat diet. Moreover, LCBE markedly improved serum lipids (including serum triglyceride, total cholesterol, low-density lipoprotein and highdensity lipoprotein) while also significantly reducing liver total cholesterol. Serum lipopolysaccharide and total bile acid in L and H groups decreased significantly compared with M group. PCR-DGGE analysis showed that the composition of gut microbiota in the treatment groups was improved. Akkermansia muciniphila was found in H group. The PCA result indicated a similar gut microbiota structure between LCBE treatment groups and normal group while the number of bands and Shannon diversity index increased significantly in the LCBE treatment groups. Finally, qPCR showed Bifidobacterium spp. increased significantly in H group compared with M group, LCBE alleviated liver steatosis and improved brown adipose tissue index.


Assuntos
Bacillus subtilis/fisiologia , Enterococcus faecium/fisiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Hiperlipidemias/prevenção & controle , Obesidade/complicações , Probióticos/administração & dosagem , Animais , Colesterol/metabolismo , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/metabolismo , Hiperlipidemias/microbiologia , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Ganho de Peso/efeitos dos fármacos
17.
J Cell Mol Med ; 25(4): 1884-1895, 2021 02.
Artigo em Inglês | MEDLINE | ID: mdl-33369150

RESUMO

Endothelial dysfunction (ED) is a key feature of diabetes and is a major cause of diabetic vasculopathy. Diabetic patients who also exhibit hyperlipidaemia suffer from accelerated vascular complications. While the deleterious effects of high glucose levels (HG) and hyperlipidaemia alone on ED are well established, the effects of combined hyperlipidaemia and HG have not been thoroughly studied. Therefore, the current study examines whether HG and hyperlipidaemia exert synergistic ED, and explores the mechanisms underlying this phenomenon. We applied multi-disciplinary approaches including cultured HUVECs and HMEC-1 as well as knockout mice CByJ.129S7(B6)-Ldlrtm1Her/J (LDLR-/- ) to investigate the mechanisms underlying combined HG and hyperlipidaemia-induced ED. Incremental doses of glucose in the presence or absence of OxLDL were added to HUVECs and HMEC-1. After 5 days, the status of nitric oxide (NO) and endothelin (ET)-1 systems as well as their signal transduction were assessed using Western blot, ELISA and immunoreactive staining. The effects of chronic combination of HG and hyperlipidaemia on endothelial integrity and function as well as alterations in circulatory NO and ET-1 systems were examined in knockout mice LDLR-/- and their wild-type. HUVEC cells exposed to HG and OxLDL displayed enhanced ET-1 production, more than HG or OxLDL when added alone. Overproduction of ET-1 stems from up-regulation of endothelin converting enzyme (ECE)-1 as observed under these conditions. In contrast, combination of HG and OxLDL dramatically decreased both total endothelial NO synthase (eNOS) by 60%, and activated eNOS (peNOS) by 80%. Moreover, NRF2 decreased by 42% and its active form (pNRF2) by 56%, as compared to baseline. Likewise, ETB levels decreased by 64% from baseline on endothelial cells. Furthermore, diabetic LDLR-/- mice displayed a higher blood pressure, plasma triglycerides, cholesterol, ET-1 and NO2/NO3 levels, when compared with normoglycemic LDLR-/- and BALB mice. Combined hyperglycaemia and hyperlipidaemia activates the ET system and attenuates the nitric oxide system with the Nrf2 signalling pathway. These findings suggest that perturbations in these paracrine systems may contribute to ED.


Assuntos
Endotélio/metabolismo , Hiperglicemia/metabolismo , Hiperlipidemias/metabolismo , Animais , Biomarcadores , Movimento Celular , Células Cultivadas , Modelos Animais de Doenças , Suscetibilidade a Doenças , Endotelinas/metabolismo , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Hiperglicemia/etiologia , Hiperlipidemias/etiologia , Lipoproteínas LDL/metabolismo , Camundongos , Camundongos Knockout , Fator 2 Relacionado a NF-E2/metabolismo , Óxido Nítrico/metabolismo
19.
Nutrients ; 12(12)2020 Dec 11.
Artigo em Inglês | MEDLINE | ID: mdl-33322540

RESUMO

Postprandial plasma glucose and triglyceride concentrations are predictive of relative cardiovascular disease (CVD) risk, and the pathogenesis of both insulin resistance and atherosclerosis has been attributed to acute states of hyperglycemia and hypertriglyceridemia. Postprandial lipemia and hyperglycemia suppress vascular reactivity and induce endothelial dysfunction. Epidemiological studies suggest that chronically-high consumption of milk and milk products is associated with a reduced risk of type 2 diabetes, metabolic syndrome, and CVD. The addition of dairy products to meals high in carbohydrates and fat may lessen these risks through reductions in postprandial glucose and triglyceride responses. Purported mechanisms include dairy proteins and bioactive compounds, which may explain the inverse relationship between dairy consumption and cardiometabolic diseases. The current review evaluates the available literature describing the relationships between metabolic dysfunction, postprandial metabolism, and vascular dysfunction and discusses the potential role of milk and dairy products in attenuating these impairments.


Assuntos
Laticínios , Hiperglicemia/prevenção & controle , Hiperlipidemias/prevenção & controle , Hipertrigliceridemia/prevenção & controle , Leite/metabolismo , Animais , Glicemia/metabolismo , Doenças Cardiovasculares/etiologia , Doenças Cardiovasculares/prevenção & controle , Endotélio Vascular/metabolismo , Fatores de Risco de Doenças Cardíacas , Humanos , Hiperglicemia/etiologia , Hiperlipidemias/etiologia , Hipertrigliceridemia/etiologia , Resistência à Insulina/fisiologia , Período Pós-Prandial , Triglicerídeos/sangue
20.
J Agric Food Chem ; 68(51): 15154-15163, 2020 Dec 23.
Artigo em Inglês | MEDLINE | ID: mdl-33300795

RESUMO

In this study, Pediococcus pentococcus PP04 isolated from the Northeast pickled cabbage had good gastrointestinal tolerance and can colonize in the intestine stably. C57BL/6N mice were fed a high-fat diet to build animal models and treated with Pediococcus pentosaceus PP04 to evaluate the antihyperlipidemia effect. After 8 weeks, the indicators of hyperlipidemia, liver injury, and inflammation were measured. The treatment of P. pentosaceus PP04 reduced the gain of total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), free fatty acids (FFAs), leptin, alanine aminotransferase (ALT), aspartate aminotransferase (AST), lipopolysaccharides (LPS), and tumor necrosis factor-α (TNF-α) significantly. The western blotting results suggested P. pentosaceus PP04 ameliorated high-fat diet-induced hyperlipidemia by the AMPK signaling pathway, which stimulated lipolysis via upregulation of PPARα and inhibited lipogenesis by downregulation of SREBP-1c, fatty acid synthase (FAS), and stearoyl-CoA desaturase-1 (SCD1) mainly. Furthermore, P. pentosaceus PP04 improved high-fat diet-induced oxidative stress effectively by triggering the Nrf2/CYP2E1 signaling pathway that enhanced the antioxidant activity including superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px).


Assuntos
Hiperlipidemias/tratamento farmacológico , Metabolismo dos Lipídeos/efeitos dos fármacos , Pediococcus pentosaceus/fisiologia , Probióticos/administração & dosagem , Animais , Dieta Hiperlipídica/efeitos adversos , Humanos , Hiperlipidemias/etiologia , Hiperlipidemias/genética , Hiperlipidemias/metabolismo , Lipogênese/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Estresse Oxidativo/efeitos dos fármacos , PPAR alfa/genética , PPAR alfa/metabolismo , Estearoil-CoA Dessaturase/genética , Estearoil-CoA Dessaturase/metabolismo , Proteína de Ligação a Elemento Regulador de Esterol 1/genética , Proteína de Ligação a Elemento Regulador de Esterol 1/metabolismo , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Triglicerídeos/metabolismo
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