RESUMO
SCOPE: Beta-carotene-15,15'-oxygenase (BCO1) and beta-carotene-9',10'-oxygenase (BCO2) metabolize lycopene to biologically active metabolites, which can ameliorate nonalcoholic fatty liver disease (NAFLD). We investigate the effects of tomato powder (TP containing substantial lycopene (2.3 mg/g)) on NAFLD development and gut microbiome in the absence of both BCO1 and BCO2 in mice. METHOD AND RESULTS: BCO1-/- /BCO2-/- double knockout mice were fed a high fat diet (HFD) alone (n = 9) or with TP feeding (n = 9) for 24 weeks. TP feeding significantly reduced pathological severity of steatosis and hepatic triglyceride levels in BCO1-/- /BCO2-/- mice (p < 0.04 vs HFD alone). This was associated with increased SIRT1 activity, nicotinamide phosphoribosyltransferase expression and AMP-activated protein kinase phosphorylation, and subsequently decreased lipogenesis, hepatic fatty acid uptake, and increasing fatty acid ß-oxidation (p < 0.05). TP feeding significantly decreased mRNA expression of proinflammatory genes (tnf-α, il-1ß, and il-6) in both liver and mesenteric adipose tissue, which were associated with increased plasma adiponectin and hepatic adiponectin receptor-2. Multiplexed 16S rRNA gene sequencing was performed using DNA extracted from cecum fecal samples. TP feeding increased microbial richness and decreased relative abundance of the genus Clostridium. CONCLUSION: Dietary TP can inhibit NAFLD independent of carotenoid cleavage enzymes, potentially through increasing SIRT1 activity and adiponectin production and decreasing Clostridium abundance.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Suplementos Nutricionais , Dioxigenases/metabolismo , Frutas/química , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Solanum lycopersicum/química , beta-Caroteno 15,15'-Mono-Oxigenase/metabolismo , Adiponectina/agonistas , Adiponectina/sangue , Adiponectina/genética , Adiponectina/metabolismo , Animais , Biomarcadores/sangue , Biomarcadores/metabolismo , Dioxigenases/genética , Disbiose/imunologia , Disbiose/metabolismo , Disbiose/microbiologia , Disbiose/prevenção & controle , Fezes/microbiologia , Microbioma Gastrointestinal , Regulação da Expressão Gênica , Gordura Intra-Abdominal/imunologia , Gordura Intra-Abdominal/metabolismo , Gordura Intra-Abdominal/patologia , Metabolismo dos Lipídeos , Fígado/imunologia , Fígado/metabolismo , Fígado/patologia , Licopeno/uso terapêutico , Masculino , Camundongos Knockout , Hepatopatia Gordurosa não Alcoólica/imunologia , Hepatopatia Gordurosa não Alcoólica/metabolismo , Hepatopatia Gordurosa não Alcoólica/microbiologia , Receptores de Adiponectina/agonistas , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Sirtuína 1/química , Sirtuína 1/metabolismo , beta-Caroteno 15,15'-Mono-Oxigenase/genéticaRESUMO
Hypertrophy of adipocytes in obese adipose tissues causes metabolic abnormality by adipocytokine dysregulation, which promotes type 2 diabetes mellitus, hypertension, and dyslipidemia. We investigated the effects of wasabi (Wasabia japonica Matsum) leaf extracts on metabolic abnormalities in SHRSP.Z-Leprfa/IzmDmcr rats (SHRSP/ZF), which are a model of metabolic syndrome. Male SHRSP/ZF rats aged 7 weeks were divided into two groups: control and wasabi leaf extract (WLE) groups, which received water or oral treatment with 4 g/kg/day WLE for 6 weeks. WLE improved the body weight gain and high blood pressure in SHRSP/ZF rats, and the plasma triglyceride levels were significantly lower in the WLE group. Adipocyte hypertrophy was markedly prevented in adipose tissue. The expression of PPARγ and subsequent downstream genes was suppressed in the WLE group adipose tissues. Our data suggest that WLE inhibits adipose hypertrophy by suppressing PPARγ expression in adipose tissue and stimulating the AMPK activity by increased adiponectin.
Assuntos
Proteínas Quinases Ativadas por AMP/genética , Adipócitos/efeitos dos fármacos , Tecido Adiposo/efeitos dos fármacos , Síndrome Metabólica/tratamento farmacológico , PPAR gama/genética , Extratos Vegetais/farmacologia , Wasabia/química , Proteínas Quinases Ativadas por AMP/metabolismo , Adipócitos/metabolismo , Adipócitos/patologia , Adiponectina/agonistas , Adiponectina/genética , Adiponectina/metabolismo , Tecido Adiposo/metabolismo , Tecido Adiposo/patologia , Administração Oral , Animais , Pressão Sanguínea/efeitos dos fármacos , Tamanho Celular/efeitos dos fármacos , Modelos Animais de Doenças , Esquema de Medicação , Regulação da Expressão Gênica , Masculino , Síndrome Metabólica/sangue , Síndrome Metabólica/genética , Síndrome Metabólica/patologia , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Folhas de Planta/química , Ratos , Ratos Transgênicos , Transdução de Sinais , Triglicerídeos/sangue , Aumento de Peso/efeitos dos fármacosRESUMO
Little is known about the effects of fatty acids on adiponectin oligomer assembly and trafficking. The aim of this study was to examine the effects of different fatty acids on adiponectin transport and secretion in differentiated 3T3-L1 adipocytes. Subcellular fractionation and immunofluorescence microscopy revealed that the majority of cellular adiponectin was located in the endoplasmic reticulum (ER). Adiponectin secretion was increased by treatment with fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), and several fatty acids changed the cellular localization of adiponectin. Adiponectin secretion has been shown to be altered by ER stress and interactions with ER chaperone proteins. However these mechanisms were not influenced by fatty acids, suggesting that alternative mechanisms must be responsible for the increased secretion of adiponectin observed with fatty acid treatment. Secretion of adiponectin was blocked by Brefeldin A, but we identified a minor pool of adiponectin that could be secreted from beyond the Brefeldin A block. Exosomes appeared to contribute to a minor amount of adiponectin secreted from the cell, and exosome release was increased by treatment with DHA. These data suggest that the ER is an important site of adiponectin accumulation and that treatment with long chain omega-3 fatty acids increases adiponectin release. Furthermore, the secretory pathway of adiponectin is complex, involving both the classical ER-Golgi pathway as well as unconventional secretory mechanisms such as an exosome-mediated pathway.
Assuntos
Adipócitos/efeitos dos fármacos , Adiponectina/metabolismo , Ácidos Docosa-Hexaenoicos/farmacologia , Ácido Eicosapentaenoico/farmacologia , Retículo Endoplasmático/efeitos dos fármacos , Exossomos/efeitos dos fármacos , Células 3T3-L1 , Adipócitos/metabolismo , Adiponectina/agonistas , Adiponectina/genética , Animais , Transporte Biológico/efeitos dos fármacos , Brefeldina A/farmacologia , Diferenciação Celular , Retículo Endoplasmático/metabolismo , Exossomos/metabolismo , Expressão Gênica , Complexo de Golgi/efeitos dos fármacos , Complexo de Golgi/metabolismo , Camundongos , Chaperonas Moleculares/genética , Chaperonas Moleculares/metabolismo , Transdução de SinaisRESUMO
Cardiovascular disease (CVD) has emerged as an important cause of death in patients with systemic lupus erythematosus (SLE). Reduced adiponectin and elevated leptin levels may contribute to CVD in SLE patients. The purpose of this study was to verify the effects of fish oil (FO) on adiponectin and leptin in patients with SLE. Biochemical and disease activity analysis were performed. Patients with SLE were divided in two groups: patients who used fish oil for four months and patients who did not use fish oil. Patients with SLE who used FO had a significant decrease in SLE disease activity index (SLEDAI) score (p Ë 0.023) in relation to baseline. SLE patients who used fish oil had increased adiponectin levels (p Ë 0.026) and decreased leptin levels (p Ë 0.024) compared to baseline values, whereas there were no differences in adiponectin and leptin levels in patients with SLE who did not use fish oil. In conclusion, the findings of increased serum adiponectin an decreased leptin levels after 120 days in the fish oil group, reinforce the importance of evaluating prospective studies of fish and fish oil fish ingestion on these adipokines in an attempt to decrease cardiovascular risk factors in patients with SLE.
Assuntos
Adiponectina/metabolismo , Ácidos Graxos Ômega-3/uso terapêutico , Leptina/metabolismo , Lúpus Eritematoso Sistêmico/tratamento farmacológico , Lúpus Eritematoso Sistêmico/metabolismo , Adiponectina/agonistas , Adulto , Antropometria , Biomarcadores/metabolismo , Pressão Sanguínea , Feminino , Óleos de Peixe/uso terapêutico , Humanos , Leptina/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Estudos ProspectivosRESUMO
PURPOSE: Coffee and green tea consumption may be associated with circulating adipokines, but data are inconsistent, scarce or lacking. We examined the association of coffee and green tea consumption with serum adiponectin, leptin, visfatin, resistin and plasminogen activator inhibitor-1 (PAI-1) among a Japanese working population. METHODS: The authors analyzed data (n = 509) from a cross-sectional survey among Japanese workers aged 20-68 years. Serum adipokines were measured using a Luminex suspension bead-based multiplexed array. Coffee and green tea consumption was assessed using a validated diet history questionnaire, and caffeine consumption from these beverages was estimated. Multiple regression analysis was performed with adjustment for potential confounding variables. RESULTS: Coffee consumption was significantly, inversely associated with leptin and PAI-1 (P for trend = 0.007 and 0.02, respectively); compared with subjects consuming <1 cup per day, those consuming ≥4 cups per day had 13 and 10 % lower means of leptin and PAI-1, respectively. Similar associations were observed for caffeine consumption (P for trend = 0.02 for both leptin and PAI-1). Additionally, we noted a significant positive association between coffee consumption and adiponectin in men (P for trend = 0.046), but not in women (P for trend = 0.43, P for interaction = 0.11). Moreover, there was a positive association between coffee consumption and resistin in current male smokers (P for trend = 0.01), but not in male non-smokers (P for trend = 0.35, P for interaction = 0.11). Green tea consumption was not associated with any adipokine. CONCLUSIONS: Higher consumption of coffee and caffeine but not green tea was associated with lower serum levels of leptin and PAI-1 in Japanese adults.
Assuntos
Adiponectina/sangue , Cafeína/efeitos adversos , Café/efeitos adversos , Comportamento Alimentar , Leptina/sangue , Inibidor 1 de Ativador de Plasminogênio/sangue , Chá/efeitos adversos , Adiponectina/agonistas , Adulto , Idoso , Biomarcadores/sangue , Cafeína/análise , Café/química , Estudos Transversais , Citocinas/sangue , Inquéritos sobre Dietas , Comportamento Alimentar/etnologia , Feminino , Manipulação de Alimentos , Humanos , Japão , Leptina/antagonistas & inibidores , Masculino , Pessoa de Meia-Idade , Nicotinamida Fosforribosiltransferase/sangue , Resistina/sangue , Caracteres Sexuais , Chá/química , Adulto JovemRESUMO
BACKGROUND AND AIMS: Little is known about the effect of various dietary fatty acids on pro- and anti-inflammatory processes. We investigated the effect of 5 oils containing various amounts of alpha-linolenic acid (ALA), linoleic acid (LA), oleic acid (OA) and docosahexaenoic acid (DHA) on plasma inflammatory biomarkers and expression levels of key inflammatory genes and transcription factors in whole blood cells. METHODS AND RESULTS: In a randomized, crossover controlled nutrition intervention, 114 adult men and women with abdominal obesity and at least one other criterion for the metabolic syndrome consumed 5 experimental isoenergetic diets for 4 weeks each, separated by 4-week washout periods. Each diet provided 60 g/3000 kcal of different oils: 1) control corn/safflower oil blend (CornSaff; LA-rich), 2) flax/safflower oil blend (FlaxSaff; ALA-rich), 3) conventional canola oil (Canola; OA-rich), 4) high oleic canola oil (CanolaOleic; highest OA content), 5) DHA-enriched high oleic canola oil (CanolaDHA; OA- and DHA-rich). Gene expression in whole blood cells was assessed in a subset of 62 subjects. CanolaDHA increased plasma adiponectin concentrations compared with the control CornSaff oil treatment (+4.5%, P = 0.04) and FlaxSaff (+6.9%, P = 0.0008). CanolaDHA also reduced relative expression levels of interleukin (IL)1B compared with CornSaff and Canola (-11% and -13%, respectively, both P = 0.03). High-sensitivity C-reactive protein concentrations were lower after Canola than after FlaxSaff (-17.8%, P = 0.047). CONCLUSION: DHA-enriched canola oil exerts anti-inflammatory effects compared with polyunsaturated fatty acids from plant sources.
Assuntos
Adiponectina/agonistas , Anti-Inflamatórios não Esteroides/uso terapêutico , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ácidos Graxos Monoinsaturados/uso terapêutico , Mediadores da Inflamação/antagonistas & inibidores , Síndrome Metabólica/prevenção & controle , Obesidade Abdominal/dietoterapia , Adiponectina/sangue , Adulto , Idoso , Anti-Inflamatórios não Esteroides/análise , Anti-Inflamatórios não Esteroides/química , Biomarcadores/sangue , Biomarcadores/metabolismo , Células Sanguíneas/imunologia , Células Sanguíneas/metabolismo , Índice de Massa Corporal , Canadá/epidemiologia , Estudos Cross-Over , Ácidos Docosa-Hexaenoicos/análise , Método Duplo-Cego , Ácidos Graxos Monoinsaturados/química , Feminino , Alimentos Fortificados , Regulação da Expressão Gênica , Humanos , Mediadores da Inflamação/sangue , Mediadores da Inflamação/metabolismo , Masculino , Síndrome Metabólica/epidemiologia , Síndrome Metabólica/etiologia , Pessoa de Meia-Idade , Obesidade Abdominal/imunologia , Obesidade Abdominal/metabolismo , Obesidade Abdominal/fisiopatologia , Pennsylvania/epidemiologia , Óleo de Brassica napus , Risco , Adulto JovemRESUMO
The thiazolidinedione (TZDs) class of drugs are very effective for the treatment of type 2 diabetes mellitus (T2DM). But due to the adverse effects of synthetic TZDs, their use is strictly regulated. The therapeutic actions of TZDs are mediated via modulation of peroxisome proliferator-activated receptor gamma (PPARγ). Naturally occurring PPARγ modulators are more desirable as they lack the serious adverse effects caused by TZDs. This has prompted the exploitation of medicinal plants used in traditional medicine, for their potential PPARγ activity. In the present work, we studied chebulagic acid (CHA) isolated from fruits of Terminalia chebula with respect to its effect on adipogenesis, glucose transport, and endocrine function of adipocyte. The mRNA expression profile of PPARγ target gene CCAAT/enhancer-binding protein alpha (C/EBP-α) was analyzed by qRT-PCR. The putative binding mode and the potential ligand-target interactions of CHA, with PPARγ was analyzed using docking software (Autodock and iGEMDOCKv2). The results showed that CHA enhances PPARγ signaling and adipogenesis dose dependently but in a moderate way, less than rosiglitazone. GLUT4 expression and adiponectin secretion was increased by CHA treatment. The mRNA expression of PPARγ target gene C/EBP-α was increased in CHA -treated adipocytes. The comparison of results of various parameters of adipogenesis, insulin sensitivity, endocrine function and molecular docking experiments of roziglitazone and chebulagic acid indicate that the latter behaves like partial PPARγ agonist which could be exploited for phytoceutical development against T2DM.
Assuntos
Adipócitos/efeitos dos fármacos , Benzopiranos/farmacologia , Glucose/metabolismo , Glucosídeos/farmacologia , Hipoglicemiantes/farmacologia , Insulina/metabolismo , PPAR gama/agonistas , Terminalia/química , Células 3T3-L1 , Adipócitos/citologia , Adipócitos/metabolismo , Adipogenia/efeitos dos fármacos , Adiponectina/agonistas , Adiponectina/genética , Adiponectina/metabolismo , Animais , Benzopiranos/isolamento & purificação , Transporte Biológico/efeitos dos fármacos , Proteínas Estimuladoras de Ligação a CCAAT/agonistas , Proteínas Estimuladoras de Ligação a CCAAT/genética , Proteínas Estimuladoras de Ligação a CCAAT/metabolismo , Diferenciação Celular , Frutas/química , Regulação da Expressão Gênica , Transportador de Glucose Tipo 4/agonistas , Transportador de Glucose Tipo 4/genética , Transportador de Glucose Tipo 4/metabolismo , Glucosídeos/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Insulina/farmacologia , Resistência à Insulina , Metanol , Camundongos , Simulação de Acoplamento Molecular , PPAR gama/genética , PPAR gama/metabolismo , Extratos Vegetais/química , Transdução de Sinais , SolventesRESUMO
Different dietary interventions have been identified as potential modifiers of adiponectin concentrations, and they may be influenced by lipid intake. We identified studies investigating the effect of dietary lipids (type/amount) on adiponectin concentrations in a systematic review with meta-analysis. A literature search was conducted until July 2013 using databases such as Medline, Embase and Scopus (MeSH terms: 'adiponectin', 'dietary lipid', 'randomized controlled trials (RCT)'). Inclusion criteria were RCT in adults analysing adiponectin concentrations with modification of dietary lipids. Among the 4930 studies retrieved, fifty-three fulfilled the inclusion criteria and were grouped as follows: (1) total dietary lipid intake; (2) dietary/supplementary n-3 PUFA; (3) conjugated linoleic acid (CLA) supplementation; (4) other dietary lipid interventions. Diets with a low fat content in comparison to diets with a high-fat content were not associated with positive changes in adiponectin concentrations (twelve studies; pooled estimate of the difference in means: -0·04 (95% CI -0·82, 0·74) µg/ml). A modest increase in adiponectin concentrations with n-3 PUFA supplementation was observed (thirteen studies; 0·27 (95% CI 0·07, 0·47) µg/ml). Publication bias was found by using Egger's test (P= 0·01) and funnel plot asymmetry. In contrast, CLA supplementation reduced the circulating concentrations of adiponectin compared with unsaturated fat supplementation (seven studies; -0·74 (95% CI -1·38, -0·10) µg/ml). However, important sources of heterogeneity were found as revealed by the meta-regression analyses of both n-3 PUFA and CLA supplementation. Results of new RCT would be necessary to confirm these findings.
Assuntos
Adiponectina/sangue , Gorduras na Dieta/administração & dosagem , Regulação para Cima , Adiponectina/agonistas , Adulto , Dieta com Restrição de Gorduras , Dieta Hiperlipídica/efeitos adversos , Gorduras na Dieta/uso terapêutico , Suplementos Nutricionais/efeitos adversos , Regulação para Baixo , Ácidos Graxos Ômega-3/uso terapêutico , Humanos , Ácidos Linoleicos Conjugados/efeitos adversos , Ácidos Linoleicos Conjugados/uso terapêutico , Ensaios Clínicos Controlados Aleatórios como Assunto , Reprodutibilidade dos TestesRESUMO
Obesity is considered to be accompanied by a chronic low-grade inflammatory state that contributes to the occurrence of many chronic diseases. Our previous study has demonstrated that histidine supplementation significantly ameliorates inflammation and oxidative stress in obese women. However, the in vivo potential mechanisms are not known. The present study was conducted to investigate the mechanisms underlying the effects of histidine on inflammation in a high-fat diet (HFD)-induced female obese rat model. An obese model was established in female Sprague-Dawley rats by HFD feeding for 8 weeks and followed by histidine supplementation for another 4 weeks. The results revealed that HFD-increased body weight and HFD-lowered serum histidine concentrations were significantly reversed by histidine supplementation (P< 0·05). In addition, the serum concentrations of TNF-α, IL-6, C-reactive protein (CRP) and malondialdehyde were significantly reduced and those of superoxide dismutase (SOD) were significantly increased by histidine supplementation when compared with those in obese rats (P< 0·05). Correspondingly, the mRNA expressions of TNF-α, IL-6 and CRP in the adipose tissue were significantly down-regulated and that of CuZnSOD was significantly up-regulated by histidine supplementation (P< 0·05). Histidine supplementation significantly reduced the HFD-induced translocation of NF-κB p65 into the nucleus (P= 0·032) by reducing the phosphorylation of the inhibitor of κBα in the adipose tissue. The results also revealed that the expression of adiponectin was markedly increased both in the serum and in the adipose tissue after histidine supplementation, accompanied by the activation of PPARγ (P= 0·021). These findings indicate that histidine is an effective candidate for ameliorating inflammation and oxidative stress in obese individuals via the NF-κB- and PPARγ-involved pathways.
Assuntos
Anti-Inflamatórios não Esteroides/uso terapêutico , Suplementos Nutricionais , Histidina/uso terapêutico , Gordura Intra-Abdominal/metabolismo , Obesidade/dietoterapia , PPAR gama/agonistas , Fator de Transcrição RelA/antagonistas & inibidores , Adiponectina/agonistas , Adiponectina/sangue , Adiponectina/genética , Adiponectina/metabolismo , Animais , Anti-Inflamatórios não Esteroides/administração & dosagem , Anti-Inflamatórios não Esteroides/sangue , Fármacos Antiobesidade/administração & dosagem , Fármacos Antiobesidade/sangue , Fármacos Antiobesidade/uso terapêutico , Proteína C-Reativa/análise , Proteína C-Reativa/genética , Proteína C-Reativa/metabolismo , Núcleo Celular/metabolismo , Citocinas/sangue , Citocinas/genética , Citocinas/metabolismo , Dieta Hiperlipídica/efeitos adversos , Feminino , Regulação da Expressão Gênica , Histidina/administração & dosagem , Histidina/sangue , Gordura Intra-Abdominal/enzimologia , Gordura Intra-Abdominal/imunologia , Obesidade/etiologia , Obesidade/imunologia , Obesidade/metabolismo , Estresse Oxidativo , PPAR gama/metabolismo , Transporte Proteico , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Superóxido Dismutase/química , Superóxido Dismutase/genética , Superóxido Dismutase/metabolismo , Fator de Transcrição RelA/metabolismoRESUMO
OBJECTIVE: The aim of this study was to investigate the protective effects of camphene on high-fat diet (HFD)-induced hepatic steatosis and insulin resistance in mice and to elucidate its mechanism of action. DESIGN AND METHODS: Male C57BL/6N mice were fed with a normal diet, HFD (20% fat and 1% cholesterol of total diet), or HFD supplemented with 0.2% camphene (CPND) for 10 weeks. RESULTS: Camphene alleviated the HFD-induced increases in liver weight and hepatic lipid levels in mice. Camphene also increased circulating adiponectin levels. To examine the direct effects of camphene on adiponectin secretion, 3T3-L1 adipocytes were incubated with camphene. Consistent with in vivo result, camphene increased adiponectin expression and secretion in 3T3-L1 adipocytes. In HFD-fed mice, camphene increased hepatic adiponectin receptor expression and AMP-activated protein kinase (AMPK) activation. Concordant with the activation of adiponectin-AMPK signaling, camphene increased hepatic expression of fatty acid oxidation-related genes and decreased those of lipogenesis-related genes in HFD-fed mice. Moreover, camphene increased insulin-signaling molecules activation and stimulated glucose transporter-2translocation to the plasma membrane in the liver. CONCLUSIONS: These results suggest camphene prevents HFD-induced hepatic steatosis and insulin resistance in mice; furthermore, these protective effects are mediated via the activation of adiponectin-AMPK signaling.
Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Adiponectina/agonistas , Suplementos Nutricionais , Fígado Gorduroso/prevenção & controle , Resistência à Insulina , Fígado/metabolismo , Terpenos/uso terapêutico , Células 3T3-L1 , Proteínas Quinases Ativadas por AMP/química , Adipócitos Brancos/metabolismo , Adipócitos Brancos/patologia , Adipogenia , Adiponectina/genética , Adiponectina/metabolismo , Animais , Antioxidantes/metabolismo , Antioxidantes/uso terapêutico , Monoterpenos Bicíclicos , Ativação Enzimática , Fígado Gorduroso/metabolismo , Fígado Gorduroso/patologia , Fígado Gorduroso/fisiopatologia , Regulação da Expressão Gênica , Fígado/patologia , Fígado/fisiopatologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Tamanho do Órgão , Distribuição Aleatória , Receptores de Adiponectina/agonistas , Receptores de Adiponectina/genética , Receptores de Adiponectina/metabolismo , Transdução de Sinais , Terpenos/metabolismoRESUMO
Our group recently demonstrated that simultaneous administration of trehalose with a high-fat diet (HFD) suppresses adipocyte hypertrophy and mitigates insulin resistance in mice. For the present study, we hypothesized that similar effects of trehalose would be observed in mice with previously-established obesity. Obese mice were fed a HFD and drinking water containing 0.3 or 2.5% (weight/volume) trehalose or distilled water (DW) ad libitum for 8 wk. After 7 wk intake of a HFD and trehalose, fasting serum insulin levels and homeostasis model assessment-insulin resistance (HOMA-IR) in the 0.3% Tre/HFD group were significantly lower than those in the DW/HFD group (p<0.05). After 8 wk of treatment, mesenteric adipocytes in the 0.3% Tre/HFD group showed significantly less hypertrophy than those in the DW/HFD group. Mechanistic analysis indicated that levels of high molecular weight (HMW) adiponectin in the serum of the 0.3% Tre/HFD group were significantly higher than those in the DW/HFD group. The expression levels of insulin receptor substrate-1 (IRS-1) and insulin receptor substrate-2 (IRS-2) messenger RNA (mRNA) in muscle were also significantly increased by trehalose intake. Our data therefore suggest that administration of trehalose to obese mice mitigates insulin resistance by suppressing adipocyte hypertrophy and increasing serum HMW adiponectin, resulting in upregulation of IRS-1, and IRS-2 expression in muscle. These results further suggest that trehalose is a functional saccharide that may be used to prevent the progression of insulin resistance.