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All living beings on earth are influenced by the circadian rhythm, the rising and the setting of the sun. The ubiquitous effect of exercise is widely believed to maximize health benefits but has not been formally investigated for cardiac responses in the exercise-induced circadian rhythms. We hypothesized that the exercise-related proteome is differentially influenced by circadian rhythm and analyzed the differences between the effects of morning and evening exercise. Twenty-four Sprague-Dawley rats were randomly divided into four groups (n = 6 per group): morning control, morning exercise, evening control, and evening exercise groups. The exercise groups were subjected to 12-week treadmill exercise (5 days/week) performed either during daytime or nighttime. After 12 weeks, the physiological characteristics (e.g., body weight, heart weight, visceral fat, and blood metabolites), cardiovascular capacity (ejection fraction (%) and fractional shortening (%)), circadian gene expression levels (clock, ball1, per1, per2, cry1, and cry2), and the proteomic data were obtained and subjected to univariate and multivariate analysis. The mRNA levels of per1 and cry2 increased in the evening group compared with those in the morning group. We also found that per2 decreased and cry2 increased in the evening exercise groups. The evening exercise groups showed more decreased triacylglycerides and increased blood insulin levels than the morning exercise group. The principal component analysis, partial least squares discriminant analysis, and orthogonal partial least squares discriminant analysis indicated that the circadian rhythm differently influenced the protein networks of the exercise groups. In the morning exercise group, the transcription-translation feedback loop (TTFL) (clock, per1, per2, cry1, and cry2) formed a protein-protein interaction network with Nme2, Hint1, Ddt, Ndufb8, Ldha, and Eef1a2. In contrast, the TTFL group appeared close to Maoa, Hist2h4, and Macrod1 in the evening exercise group. Interestingly, the evening exercise group decreased the mRNA level of per2 but not per1. Per1 and Per2 are known to transport Cry1 and Cry2 into the nucleus. Taken together, we summarized the characteristics of enriched proteins in the aspect of their molecular function, cellular component, and biological process. Our results might provide a better understanding of the circadian effect on exercise-related proteins.
Assuntos
Adaptação Fisiológica , Ritmo Circadiano , Miocárdio/metabolismo , Condicionamento Físico Animal , Proteoma/metabolismo , Animais , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/genética , Peptídeos e Proteínas de Sinalização do Ritmo Circadiano/metabolismo , Coração/fisiologia , Masculino , Mapas de Interação de Proteínas , Proteoma/genética , Ratos , Ratos Sprague-DawleyRESUMO
Involuntary physical activity induced by the avoidance of electrical shock leads to improved endurance exercise capacity in animals. However, it remains unknown whether voluntary stand-up physical activity (SPA) without forced simulating factors improves endurance exercise capacity in animals. We examined the eff ects of SPA on body weight, cardiac function, and endurance exercise capacity for 12 weeks. Twelve male Sprague-Dawley rats (aged 8 weeks, n=6 per group) were randomly assigned to a control group (CON) or a voluntary SPA group. The rats were induced to perform voluntary SPA (lifting a load equal to their body weight), while the food height (18.0 cm) in cages was increased progressively by 3.5 every 4 weeks until it reached 28.5 cm for 12 weeks. The SPA group showed a lower body weight compared to the CON group, but voluntary SPA did not affect the skeletal muscle and heart weights, food intake, and echocardiography results. Although the SPA group showed higher grip strength, running time, and distance compared to the CON group, the level of irisin, corticosterone, genetic expression of mitochondrial biogenesis, and nuclei numbers were not affected. These findings show that voluntary SPA without any forced stimuli in rats can eff ectively reduce body weight and enhance endurance exercise capacity, suggesting that it may be an important alternative strategy to enhance endurance exercise capacity.
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The differential ability of various milk protein fractions to stimulate muscle protein synthesis (MPS) has been previously described, with whey protein generally considered to be superior to other fractions. However, the relative ability of a whole milk protein to stimulate MPS has not been compared to whey. Sixteen healthy middle-aged males ingested either 20 g of milk protein (n = 8) or whey protein (n = 8) while undergoing a primed constant infusion of ring (13)C6 phenylalanine. Muscle biopsies were obtained 120 min prior to consumption of the protein and 90 and 210 min afterwards. Resting myofibrillar fractional synthetic rates (FSR) were 0.019% ± 0.009% and 0.021% ± 0.018% h(-1) in the milk and whey groups respectively. For the first 90 min after protein ingestion the FSR increased (p < 0.001) to 0.057% ± 0.018% and 0.052% ± 0.024% h(-1) in the milk and whey groups respectively with no difference between groups (p = 0.810). FSR returned to baseline in both groups between 90 and 210 min after protein ingestion. Despite evidence of increased rate of digestion and leucine availability following the ingestion of whey protein, there was similar activation of MPS in middle-aged men with either 20 g of milk protein or whey protein.
Assuntos
Proteínas do Leite/farmacologia , Proteínas Musculares/metabolismo , Músculos/metabolismo , Biossíntese de Proteínas/efeitos dos fármacos , Humanos , Masculino , Pessoa de Meia-Idade , Miofibrilas/metabolismo , Proteínas do Soro do Leite/farmacologiaRESUMO
Echinochrome A (Echi A) improves mitochondrial function in the heart; however, its effects on skeletal muscle are still unclear. We hypothesized that Echi A administration during short-term exercise may improve exercise capacity. Twenty-four male Sprague-Dawley rats were randomly divided into the following groups: control group (CG), Echi A-treated group (EG), aerobic exercise group (AG), and aerobic exercise treated with Echi A group (AEG) (n = 6 per group). Echi A was administered intra-peritoneally (0.1 mg/kg of Echi A in 300 µL phosphate-buffered saline) daily 30 min before each exercise training. The AG and AEG groups performed treadmill running (20 m/min, 60 min/day) five days/week for two weeks. The exercise capacity was significantly higher in the AG and AEG groups compared to other groups. Interestingly, the exercise capacity increased more effectively in the AEG group. The body weight in the EG tended to be slightly lower than that in the other groups. There were no significant changes in the plasma lipids among the groups. However, the gastrocnemius muscle mitochondria content was greater in the EG and AEG groups. These findings show that Echi A administration after short-term endurance training enhances exercise capacity, which was associated with an increase in skeletal muscle mitochondrial content.
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Naftoquinonas/farmacologia , Condicionamento Físico Animal , Resistência Física/efeitos dos fármacos , Animais , Peso Corporal/efeitos dos fármacos , Coração/anatomia & histologia , Coração/efeitos dos fármacos , Lipídeos/sangue , Masculino , Estrutura Molecular , Músculo Esquelético/efeitos dos fármacos , Naftoquinonas/química , Tamanho do Órgão , Ratos , Ratos Sprague-Dawley , Ouriços-do-Mar/químicaRESUMO
Worldwide estimates predict 2 billion people will be aged over 65 years by 2050. A major current challenge is maintaining mobility and quality of life into old age. Impaired mobility is often a precursor of functional decline, disability and loss of independence. Sarcopenia which represents the age-related decline in muscle mass is a well-established factor associated with mobility limitations in older adults. However, there is now evidence that not only changes in muscle mass but other factors underpinning muscle quality including composition, metabolism, aerobic capacity, insulin resistance, fat infiltration, fibrosis and neural activation may also play a role in the decline in muscle function and impaired mobility associated with ageing. Importantly, changes in muscle quality may precede loss of muscle mass and therefore provide new opportunities for the assessment of muscle quality particularly in middle-aged adults who could benefit from interventions to improve muscle function. This review will discuss the accumulating evidence that in addition to muscle mass, factors underpinning muscle quality influence muscle function and mobility with age. Further development of tools to assess muscle quality in community settings is needed. Preventative diet, exercise or treatment interventions particularly in middle-aged adults at the low end of the spectrum of muscle function may help preserve mobility in later years and improve healthspan.
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Rotavirus (RV) is a leading cause of morbidity and mortality in children younger than 5 years of age, presenting commonly with diarrhoeal symptoms. In a prospective 12-week double-blind randomised controlled trial we assessed acceptability and efficacy of a high-ganglioside complex milk lipid (CML) for prevention of RV infection in 450 infants, ages 8 to 24 months, at 3 sites in northern India. Prevalence of diarrhoea and RV was unseasonably low at baseline (all-cause diarrhoea [ACD], nâ=â16; RV diarrhoea [RVD], nâ=â2; RV infection, RV positive [RV+], nâ=â20) and throughout the trial, with only 110 total episodes of ACD for 12 weeks (CML, nâ=â62; control, nâ=â48) of which 10 were RVD (CML, nâ=â4; control, nâ=â6). Mean duration that RVD persisted was lower in the CML group (2.3â±â0.5 days) than that in the control group (3.8â±â1.3 days, Pâ=â0.03), but only 3 of 450 end of trial stool samples were identified as RV+ (<1%; CML, nâ=â2; control, nâ=â1). This hampered the assessment of efficacy of CML, despite the large a priori determined sample size. During the trial similar numbers of infants reported adverse events (AEs: CML 41%, control 46%), with the majority of events classified as mild and not related to the intervention. In conclusion, further clinical trials against a higher background of seasonal prevalence are necessary to assess efficacy of this nutritional intervention to prevent RVD. More important, however, high-ganglioside CML was acceptable for long-term consumption in infants ages 8 to 24 months.
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Diarreia/prevenção & controle , Gangliosídeos/uso terapêutico , Leite/química , Infecções por Rotavirus/prevenção & controle , Rotavirus , Animais , Bovinos , Pré-Escolar , Diarreia/etiologia , Diarreia/virologia , Método Duplo-Cego , Fezes/virologia , Feminino , Gangliosídeos/efeitos adversos , Humanos , Índia , Lactente , Masculino , Prevalência , Estudos Prospectivos , Infecções por Rotavirus/complicações , Infecções por Rotavirus/virologia , Estações do Ano , Resultado do Tratamento , Adulto JovemRESUMO
Progressive age-related changes in skeletal muscle mass and composition, underpin decreases in muscle function, which can inturn lead to impaired mobility and quality of life in older adults. MicroRNAs (miRNAs) are important post-transcriptional regulators of gene expression in skeletal muscle and are associated with aging. Accumulating evidence suggests that miRNAs play an important role in the age-related changes in skeletal muscle mass, composition and function. At the cellular level, miRNAs have been demonstrated to regulate muscle cell proliferation and differentiation. Furthermore, miRNAs are involved in the transitioning of muscle stem cells from a quiescent, to either an activated or senescence state. Evidence from animal and human studies has shown miRNAs are modulated in muscle atrophy and hypertrophy. In addition, miRNAs have been implicated in changes in muscle fiber composition, fat infiltration and insulin resistance. Both exercise and dietary interventions can combat age-related changes in muscle mass, composition and function, which may be mediated by miRNA modulation in skeletal muscle. Circulating miRNA species derived from myogenic cell populations represent potential biomarkers of aging muscle and the molecular responses to exercise or diet interventions, but larger validation studies are required. In future therapeutic approaches targeting miRNAs, either through exercise, diet or drugs may be able to slow down or prevent the age-related changes in skeletal muscle mass, composition, function, hence help maintain mobility and quality of life in old age.
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Envelhecimento/metabolismo , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Adaptação Fisiológica , Diferenciação Celular , Senescência Celular , Dieta , Exercício Físico/fisiologia , Humanos , Resistência à Insulina , Metabolismo dos Lipídeos , Músculo Esquelético/citologia , Atrofia Muscular/metabolismo , Células-Tronco/metabolismoRESUMO
Worldwide obesity and related comorbidities are increasing, but identifying new therapeutic targets remains a challenge. A plethora of microarray studies in diet-induced obesity models has provided large datasets of obesity associated genes. In this review, we describe an approach to examine the underlying molecular network regulating obesity, and we discuss interactions between obesity candidate genes. We conducted network analysis on functional protein-protein interactions associated with 25 obesity candidate genes identified in a literature-driven approach based on published microarray studies of diet-induced obesity. The obesity candidate genes were closely associated with lipid metabolism and inflammation. Peroxisome proliferator activated receptor gamma (Pparg) appeared to be a core obesity gene, and obesity candidate genes were highly interconnected, suggesting a coordinately regulated molecular network in adipose tissue. In conclusion, the current network analysis approach may help elucidate the underlying molecular network regulating obesity and identify anti-obesity targets for therapeutic intervention.
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Tecido Adiposo Branco , Dieta Hiperlipídica , Obesidade/etiologia , Obesidade/genética , Adipocinas/fisiologia , Tecido Adiposo Branco/química , Tecido Adiposo Branco/metabolismo , Animais , Metabolismo Energético/genética , Inflamação/genética , Metabolismo dos Lipídeos/genética , Camundongos , Camundongos Endogâmicos C57BL , Nutrigenômica , Estresse Oxidativo/genética , PPAR gama/genética , PPAR gama/fisiologia , Análise Serial de ProteínasRESUMO
AIMS: This study investigated the hepatoprotective effects of low doses of curcumin against liver damage induced by chronic alcohol intake and a high-fat diet. We also examined several potential underlying mechanisms including action on alcohol metabolism, antioxidant activity, AMPK level and lipid metabolism. MAIN METHOD: Alcohol (25% v/v, 5 g/kg body weight) was orally administered once a day for 6 weeks to mice fed a high-fat diet with or without two different doses of curcumin (0.02% and 0.05%, wt/wt). KEY FINDINGS: Curcumin significantly decreased the plasma aspartate aminotransferase, alanine aminotransferase, lactate dehydrogenase and alkaline phosphatase activities (p<0.05) and prevented hepatic steatosis compared with the alcohol control group. Curcumin significantly reversed the alcohol-induced inhibition of the alcohol dehydrogenase, aldehyde dehydrogenase 2 and antioxidant enzyme activities as well as the activation of cytochrome P4502E1 and promotion of lipid peroxidation (p<0.05). Curcumin significantly increased the hepatic total AMPK protein level and concomitantly suppressed the fatty acid synthase and phosphatidate phosphohydrolase activities compared with the alcohol control group (p<0.05). Furthermore, curcumin significantly lowered the plasma leptin, free fatty acids and triglycerides levels and hepatic lipid levels (p<0.05). SIGNIFICANCE: These findings indicate that low doses of curcumin may protect against liver damage caused by chronic alcohol intake and a high-fat diet partly by modulating the alcohol metabolic enzyme activity, the antioxidant activity and the lipid metabolism. Therefore, curcumin may provide a promising natural therapeutic strategy against liver disease.
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Proteínas Quinases Ativadas por AMP/fisiologia , Curcumina/administração & dosagem , Citocromo P-450 CYP2E1/fisiologia , Etanol/metabolismo , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/prevenção & controle , Animais , Relação Dose-Resposta a Droga , Etanol/administração & dosagem , Etanol/toxicidade , Masculino , Redes e Vias Metabólicas/efeitos dos fármacos , Redes e Vias Metabólicas/fisiologia , Camundongos , Camundongos Endogâmicos ICRRESUMO
Epidemiological evidence shows that consumption of dairy products is associated with decreased prevalence of metabolic related disorders, whilst evidence from experimental studies points towards dairy protein as a dietary component which may aid prevention of type 2 diabetes (T2DM). Poor metabolic health is a common characteristic of overweight, obesity and aging, and is the forerunner of T2DM and cardiovascular disease (CVD), and an ever increasing global health issue. Progressive loss of metabolic control is evident from a blunting of carbohydrate, fat and protein metabolism, which is commonly manifested through decreased insulin sensitivity, inadequate glucose and lipid control, accompanied by a pro-inflammatory environment and hypertension. Adverse physiological changes such as excess visceral adipose tissue deposition and expansion, lipid overspill and infiltration into liver, muscle and other organs, and sarcopaenia or degenerative loss of skeletal muscle mass and function all underpin this adverse profile. 'Sarcobesity' and sarcopaenic diabetes are rapidly growing health issues. As well as through direct mechanisms, dairy protein may indirectly improve metabolic health by aiding loss of body weight and fat mass through enhanced satiety, whilst promoting skeletal muscle growth and function through anabolic effects of dairy protein-derived branch chain amino acids (BCAAs). BCAAs enhance muscle protein synthesis, lean body mass and skeletal muscle metabolic function. The composition and processing of dairy protein has an impact on digestion, absorption, BCAA kinetics and function, hence the optimisation of dairy protein composition through selection and combination of specific protein components in milk may provide a way to maximize benefits for metabolic health.
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OBJECTIVE: To investigate the functional effects of probiotic treatment on the gut microbiota, as well as liver and adipose gene expression in diet-induced obese mice. DESIGN: Male C57BL/6J mice were fed a high-fat diet (HFD) for 8 weeks to induce obesity, and then randomized to receive HFD+probiotic (Lactobacillus curvatus HY7601 and Lactobacillus plantarum KY1032, nâ=â9) or HFD+placebo (nâ=â9) for another 10 weeks. Normal diet (ND) fed mice (nâ=â9) served as non-obese controls. RESULTS: Diet-induced obese mice treated with probiotics showed reduced body weight gain and fat accumulation as well as lowered plasma insulin, leptin, total-cholesterol and liver toxicity biomarkers. A total of 151,061 pyrosequencing reads for fecal microbiota were analyzed with a mean of 6,564, 5,274 and 4,464 reads for the ND, HFD+placebo and HFD+probiotic groups, respectively. Gut microbiota species were shared among the experimental groups despite the different diets and treatments. The diversity of the gut microbiota and its composition were significantly altered in the diet-induced obese mice and after probiotic treatment. We observed concurrent transcriptional changes in adipose tissue and the liver. In adipose tissue, pro-inflammatory genes (TNFα, IL6, IL1ß and MCP1) were down-regulated in mice receiving probiotic treatment. In the liver, fatty acid oxidation-related genes (PGC1α, CPT1, CPT2 and ACOX1) were up-regulated in mice receiving probiotic treatment. CONCLUSIONS: The gut microbiota of diet-induced obese mice appears to be modulated in mice receiving probiotic treatment. Probiotic treatment might reduce diet-induced obesity and modulate genes associated with metabolism and inflammation in the liver and adipose tissue.
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Dieta/efeitos adversos , Intestinos/efeitos dos fármacos , Intestinos/microbiologia , Lactobacillus plantarum/fisiologia , Obesidade/dietoterapia , Obesidade/microbiologia , Probióticos/farmacologia , Adipócitos/efeitos dos fármacos , Adipócitos/metabolismo , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Animais , Biodiversidade , Peso Corporal/efeitos dos fármacos , Colesterol/sangue , Regulação da Expressão Gênica/efeitos dos fármacos , Hormônios/sangue , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Metagenoma/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/etiologia , Obesidade/metabolismo , Probióticos/uso terapêuticoRESUMO
AIM: To investigate the effect of novel probiotics on the clinical characteristics of high-fructose induced metabolic syndrome. METHODS: Male Wistar rats aged 4 wk were fed a 70% w/w high-fructose diet (n = 27) or chow diet (n = 9) for 3 wk to induce metabolic syndrome, the rats were then randomized into groups and administered probiotic [Lactobacillus curvatus (L. curvatus) HY7601 and Lactobacillus plantarum (L. plantarum) KY1032] at 10(9) cfu/d or 10(10) cfu/d or placebo by oral gavage for 3 wk. Food intake and body weight were measured once a week. After 6 wk, the rats were fasted for 12 h, then anesthetized with diethyl ether and sacrificed. Blood samples were taken from the inferior vena cava for plasma analysis of glucose, insulin, C-peptide, total-cholesterol, triglycerides and thiobarbituric acid-reacting substances. Real-time polymerase chain reaction was performed using mouse-specific Taqman probe sets to assess genes related to fatty acid ß-oxidation, lipogenesis and cholesterol metabolism in the liver. Target gene expression was normalized to the housekeeping gene, glyceraldehyde-3-phosphate dehydrogenase. RESULTS: Rodents fed a high-fructose diet developed clinical characteristics of the metabolic syndrome including increased plasma glucose, insulin, triglycerides, total cholesterol and oxidative stress levels, as well as increased liver mass and liver lipids compared to chow fed controls. Probiotic treatment (L. curvatus HY7601 and L. plantarum KY1032) at high (10(10) cfu/d) or low dosage (10(9) cfu/d) lowered plasma glucose, insulin, triglycerides and oxidative stress levels. Only high-dose probiotic treatment reduced liver mass and liver cholesterol. Probiotic treatment reduced lipogenesis via down-regulation of SREBP1, FAS and SCD1 mRNA levels and increased ß-oxidation via up-regulation of PPARα and CPT2 mRNA levels. CONCLUSION: Probiotic L. curvatus HY7601 and L. plantarum KY1032 combined suppressed the clinical characteristics of high-fructose-induced metabolic syndrome, therefore, may provide a natural alternative for the treatment of diet-induced metabolic syndrome.
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Carboidratos da Dieta/efeitos adversos , Frutose/efeitos adversos , Lactobacillus/classificação , Síndrome Metabólica/etiologia , Síndrome Metabólica/prevenção & controle , Probióticos/uso terapêutico , Animais , Glicemia/metabolismo , Peptídeo C/sangue , Colesterol/sangue , Modelos Animais de Doenças , Insulina/sangue , Masculino , Síndrome Metabólica/sangue , Estresse Oxidativo/efeitos dos fármacos , Ratos , Substâncias Reativas com Ácido Tiobarbitúrico/metabolismo , Triglicerídeos/sangueRESUMO
Prolonged high-fat diet leads to the development of obesity and multiple comorbidities including non-alcoholic steatohepatitis (NASH), but the underlying molecular basis is not fully understood. We combine molecular networks and time course gene expression profiles to reveal the dynamic changes in molecular networks underlying diet-induced obesity and NASH. We also identify hub genes associated with the development of NASH. Core diet-induced obesity networks were constructed using Ingenuity pathway analysis (IPA) based on 332 high-fat diet responsive genes identified in liver by time course microarray analysis (8 time points over 24 weeks) of high-fat diet-fed mice compared to normal diet-fed mice. IPA identified five core diet-induced obesity networks with time-dependent gene expression changes in liver. These networks were associated with cell-to-cell signaling and interaction (Network 1), lipid metabolism (Network 2), hepatic system disease (Network 3 and 5), and inflammatory response (Network 4). When we merged these core diet-induced obesity networks, Tlr2, Cd14, and Ccnd1 emerged as hub genes associated with both liver steatosis and inflammation and were altered in a time-dependent manner. Further, protein-protein interaction network analysis revealed Tlr2, Cd14, and Ccnd1 were interrelated through the ErbB/insulin signaling pathway. Dynamic changes occur in molecular networks underlying diet-induced obesity. Tlr2, Cd14, and Ccnd1 appear to be hub genes integrating molecular interactions associated with the development of NASH. Therapeutics targeting hub genes and core diet-induced obesity networks may help ameliorate diet-induced obesity and NASH.
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BACKGROUND: Visceral white adipose tissue (WAT) hypertrophy, adipokine production, inflammation and fibrosis are strongly associated with obesity, but the time-course of these changes in-vivo are not fully understood. Therefore, the aim of this study was to establish the time-course of changes in adipocyte morphology, adipokines and the global transcriptional landscape in visceral WAT during the development of diet-induced obesity. RESULTS: C57BL/6 J mice were fed a high-fat diet (HFD) or normal diet (ND) and sacrificed at 8 time-points over 24 weeks. Excessive fat accumulation was evident in visceral WAT depots (Epidydimal, Perirenal, Retroperitoneum, Mesentery) after 2-4 weeks. Fibrillar collagen accumulation was evident in epidydimal adipocytes at 24 weeks. Plasma adipokines, leptin, resistin and adipsin, increased early and time-dependently, while adiponectin decreased late after 20 weeks. Only plasma leptin and adiponectin levels were associated with their respective mRNA levels in visceral WAT. Time-course microarrays revealed early and sustained activation of the immune transcriptome in epididymal and mesenteric depots. Up-regulated inflammatory genes included pro-inflammatory cytokines, chemokines (Tnf, Il1rn, Saa3, Emr1, Adam8, Itgam, Ccl2, 3, 4, 6, 7 and 9) and their upstream signalling pathway genes (multiple Toll-like receptors, Irf5 and Cd14). Early changes also occurred in fibrosis, extracellular matrix, collagen and cathepsin related-genes, but histological fibrosis was only visible in the later stages. CONCLUSIONS: In diet-induced obesity, early activation of TLR-mediated inflammatory signalling cascades by CD antigen genes, leads to increased expression of pro-inflammatory cytokines and chemokines, resulting in chronic low-grade inflammation. Early changes in collagen genes may trigger the accumulation of ECM components, promoting fibrosis in the later stages of diet-induced obesity. New therapeutic approaches targeting visceral adipose tissue genes altered early by HFD feeding may help ameliorate the deleterious effects of diet-induced obesity.
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Adipocinas/metabolismo , Fibrose/genética , Obesidade/genética , Transcriptoma/genética , Adiponectina/sangue , Adiponectina/genética , Tecido Adiposo Branco/metabolismo , Animais , Catepsinas/genética , Catepsinas/metabolismo , Quimiocinas/genética , Quimiocinas/metabolismo , Fator D do Complemento/genética , Fator D do Complemento/metabolismo , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica , Fibrose/metabolismo , Leptina/sangue , Leptina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/imunologia , Obesidade/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Resistina/sangue , Resistina/genética , Transdução de Sinais , Fatores de TempoRESUMO
SCOPE: This study investigated the effects of resveratrol (RV) on diabetes-related metabolic changes in a spontaneous model of type 2 diabetes, as well as activation of AMP-activated protein kinase (AMPK) and downstream targets. METHODS AND RESULTS: C57BL/KsJ-db/db mice were fed a normal diet with RV (0.005% and 0.02%, w/w) or rosiglitazone (RG, 0.001%, w/w) for 6 weeks. Both doses of RV significantly decreased blood glucose, plasma free fatty acid, triglyceride, apo B/apo AÐ levels and increased plasma adiponectin levels. RV activated AMPK and downstream targets leading to decreased blood HbA1c levels, hepatic gluconeogenic enzyme activity, and hepatic glycogen, while plasma insulin levels, pancreatic insulin protein, and skeletal muscle GLUT4 protein were higher after RV supplementation. The high RV dose also significantly increased hepatic glycolytic gene expression and enzyme activity, along with skeletal muscle glycogen synthase protein expression, similar to RG. Furthermore, RV dose dependently decreased hepatic triglyceride content and phosphorylated I kappa B kinase (p-IKK) protein expression, while hepatic uncoupling protein (UCP) and skeletal muscle UCP expression were increased. CONCLUSION: RV potentiates improving glycemic control, glucose uptake, and dyslipidemia, as well as protecting against pancreatic ß-cell failure in a spontaneous type 2 diabetes model. Dietary RV has potential as an antidiabetic agent via activation of AMPK and its downstream targets.
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Proteínas Quinases Ativadas por AMP/metabolismo , Diabetes Mellitus Tipo 2/tratamento farmacológico , Diabetes Mellitus Tipo 2/metabolismo , Estilbenos/farmacologia , Adiponectina/sangue , Animais , Glicemia/metabolismo , Peso Corporal/efeitos dos fármacos , Suplementos Nutricionais , Dislipidemias/tratamento farmacológico , Dislipidemias/metabolismo , Transportador de Glucose Tipo 4/metabolismo , Hemoglobinas Glicadas/metabolismo , Glicogênio/metabolismo , Insulina/metabolismo , Secreção de Insulina , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Músculo Esquelético/efeitos dos fármacos , Músculo Esquelético/metabolismo , Resveratrol , Rosiglitazona , Tiazolidinedionas/farmacologia , Triglicerídeos/sangueRESUMO
SCOPE: Atherosclerosis is a major cause of cardiovascular disease caused by high cholesterol. Stains are widely prescribed to lower cholesterol levels, but natural dietary compounds may also be effective. Therefore, we studied the effect of the natural dietary compound curcumin on atherosclerosis and its underlying mechanisms based on plasma and hepatic lipid metabolism. METHODS AND RESULTS: LDLR(-/-) mice were fed a high-cholesterol diet and treated with curcumin, lovastatin or control (n=10 per group) for 18 wk. Aortic arch sections revealed curcumin ameliorated early atherosclerotic lesions, lipid infiltration, ICAM-1 and VCAM-1 localization, similar to lovastatin treatment. Furthermore, curcumin lowered plasma cholesterol, triglycerides, LDL cholesterol and Apo B levels as well as CETP activity, while curcumin increased plasma HDL cholesterol and liver Apo A-I expression, similar to lovastatin treatment. Curcumin caused transcriptional inhibition of HMG-CoA reductase, independent of ACAT1 and ACAT2 expression. Hepatic PPARα and LXRα expression was upregulated by curcumin treatment. Hepatic complement factor D (Cfd) and systemic CRP levels, markers of immune complement pathway activation, were significantly reduced by curcumin treatment. CONCLUSION: Long-term curcumin treatment lowers plasma and hepatic cholesterol and suppresses early atherosclerotic lesions comparable to the protective effects of lovastatin. The anti-atherogenic effect of curcumin is mediated via multiple mechanisms including altered lipid, cholesterol and immune gene expression.
Assuntos
Aterosclerose/prevenção & controle , Colesterol/metabolismo , Curcumina/administração & dosagem , Lipoproteínas/metabolismo , Fígado/efeitos dos fármacos , Acetil-CoA C-Acetiltransferase/genética , Acetil-CoA C-Acetiltransferase/metabolismo , Animais , Apolipoproteína A-I/genética , Apolipoproteína A-I/metabolismo , Apolipoproteínas B/sangue , Apolipoproteínas B/efeitos dos fármacos , Colesterol na Dieta , HDL-Colesterol/sangue , HDL-Colesterol/efeitos dos fármacos , LDL-Colesterol/sangue , LDL-Colesterol/efeitos dos fármacos , Hidroximetilglutaril-CoA Redutases/metabolismo , Inibidores de Hidroximetilglutaril-CoA Redutases/metabolismo , Molécula 1 de Adesão Intercelular/efeitos dos fármacos , Molécula 1 de Adesão Intercelular/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/metabolismo , Receptores X do Fígado , Lovastatina/administração & dosagem , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Receptores Nucleares Órfãos/genética , Receptores Nucleares Órfãos/metabolismo , PPAR alfa/genética , PPAR alfa/metabolismo , Triglicerídeos/sangue , Regulação para Cima , Molécula 1 de Adesão de Célula Vascular/efeitos dos fármacos , Molécula 1 de Adesão de Célula Vascular/metabolismoRESUMO
BACKGROUND: Natural food supplements with high flavonoid content are often claimed to promote weight-loss and lower plasma cholesterol in animal studies, but human studies have been more equivocal. The aim of this study was firstly to determine the effectiveness of natural food supplements containing Glycine max leaves extract (EGML) or Garcinia cambogia extract (GCE) to promote weight-loss and lower plasma cholesterol. Secondly to examine whether these supplements have any beneficial effect on lipid, adipocytokine or antioxidant profiles. METHODS: Eighty-six overweight subjects (Male:Female = 46:40, age: 20~50 yr, BMI > 23 < 29) were randomly assigned to three groups and administered tablets containing EGML (2 g/day), GCE (2 g/day) or placebo (starch, 2 g/day) for 10 weeks. At baseline and after 10 weeks, body composition, plasma cholesterol and diet were assessed. Blood analysis was also conducted to examine plasma lipoproteins, triglycerides, adipocytokines and antioxidants. RESULTS: EGML and GCE supplementation failed to promote weight-loss or any clinically significant change in %body fat. The EGML group had lower total cholesterol after 10 weeks compared to the placebo group (p < 0.05). EGML and GCE had no effect on triglycerides, non-HDL-C, adipocytokines or antioxidants when compared to placebo supplementation. However, HDL-C was higher in the EGML group (p < 0.001) after 10 weeks compared to the placebo group. CONCLUSIONS: Ten weeks of EGML or GCE supplementation did not promote weight-loss or lower total cholesterol in overweight individuals consuming their habitual diet. Although, EGML did increase plasma HDL-C levels which is associated with a lower risk of atherosclerosis.
Assuntos
Adipocinas/sangue , Antioxidantes/metabolismo , Colesterol/sangue , Garcinia cambogia , Glycine max , Sobrepeso/tratamento farmacológico , Redução de Peso/efeitos dos fármacos , Alanina Transaminase/sangue , Aspartato Aminotransferases/sangue , Suplementos Nutricionais , Feminino , Humanos , Lipídeos/sangue , Masculino , Sobrepeso/sangue , Extratos Vegetais/uso terapêutico , Folhas de Planta/químicaRESUMO
SCOPE: This study investigated the global transcriptional and metabolic changes occurring at multiple time points over 24 wk in response to a high-fat diet (HFD). METHODS AND RESULTS: C57BL/6J mice were fed a HFD or normal diet (ND) over 24 wk. HFD-fed mice developed early clinical indicators of obesity-related co-morbidities including fatty liver, insulin resistance, hyperglycemia and hypercholesterolemia. Time-course microarray analysis at eight time points over 24 wk identified 332 HFD responsive genes as potential targets to counteract diet-induced obesity (DIO) and related co-morbidities. Glucose regulating enzyme activity and gene expression were altered early in the HFD-fed mice. Fatty acid (FA) and triglyceride (TG) accumulation in combination with inflammatory changes appear to be likely candidates contributing to hepatic insulin resistance. Cidea seemed to be one of representative genes related to these changes. CONCLUSION: Global transcriptional and metabolic profiling across multiple time points in liver revealed potential targets for nutritional interventions to reverse DIO. In future, new approaches targeting HFD responsive genes and hepatic metabolism could help ameliorate the deleterious effects of an HFD and DIO-related complication.
Assuntos
Dieta Hiperlipídica/efeitos adversos , Perfilação da Expressão Gênica , Fígado/metabolismo , Obesidade/etiologia , Animais , Antioxidantes/metabolismo , Peso Corporal/genética , Enzimas/metabolismo , Fígado Gorduroso/metabolismo , Regulação da Expressão Gênica , Glucose/metabolismo , Teste de Tolerância a Glucose , Hipercolesterolemia/metabolismo , Hiperglicemia/metabolismo , Resistência à Insulina , Metabolismo dos Lipídeos , Lipídeos/sangue , Fígado/fisiologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Obesidade/metabolismo , Análise de Sequência com Séries de Oligonucleotídeos , Fatores de Tempo , Triglicerídeos/metabolismoRESUMO
The need for greater sensitivity in exercise performance measures is of particular importance in nutritional intervention studies and such measures have been investigated in trained cyclists, but not in those who have no experience of laboratory testing and/or the need to pace their effort. The aim of the present study was to evaluate a mixed design approach (constant load then time-trial) endurance type cycle ergometer protocol using recreationally active participants not well accustomed to cycling. Seven participants including one female (age 25 +/- 5 years; body mass 74.4 +/- 9.3 kg; peak VO(2) 3.91 +/- 0.96 l) completed four repeat cycle tests. The test consisted of a "pre-load" (60 min at 65% of peak VO(2)) followed by a 20 min time trial (performance measure). Reliability for the performance measure was assessed by calculating the individual participant coefficient of variation (CV) and a mean CV for the group. Excluding a familiarisation trial, mean CV for the group was 3.4% (95% confidence interval between 2.0 and 10.1%). It is concluded that the performance test described can be used in recreationally active young adults with lower variation after one familiarisation trial. The protocol might be used to evaluate an intervention if changes in performance are expected to be greater than 3.4%, or greater than around 7% if a signal to noise ratio of 2: 1 was to be considered appropriate.