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1.
J Appl Microbiol ; 121(3): 800-10, 2016 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-27111464

RESUMEN

AIM: Nonalcoholic hepatic fat accumulation has been hypothesized to be associated with alterations in gut microbiota composition, although mechanistic explanations for this link are largely insufficient. The aim of this study was to elucidate the microbiota-driven mechanisms involved in the development of nonalcoholic hepatic steatosis. METHODS AND RESULTS: Ob/ob mice and their wild-type lean control mice were fed an AIN-93G diet for 12 weeks. Faecal microbiota composition, faecal bile acid (BA) profile and intestinal and hepatic markers of BA metabolism were analysed. Ob/ob mice had significantly less faecal taurine-conjugated BAs compared to their lean controls. The proportions of butyrate-producing bacteria were lower in ob/ob mice compared to those in lean mice. Intestinal expression of farnesoid X receptor (FXR) mRNA was significantly higher, whereas hepatic expression of cholesterol-7α-hydroxylase 1 (CYP7A1) and small heterodimer partner (SHP) were significantly lower in ob/ob mice compared to those in control mice. CONCLUSION: Microbiota-associated BAs deconjugation may induce nonalcoholic fatty liver disease (NAFLD) by activating intestinal FXR signalling and blocking hepatic FXR-SHP pathway, thereby accelerating fat synthesis. SIGNIFICANCE AND IMPACT OF THE STUDY: We provided evidences that changes in the gut microbiota and their metabolites can alter the profile of BAs, thereby providing a mechanism by which an altered microbiota profile contributes to the development of NAFLD.


Asunto(s)
Ácidos y Sales Biliares/metabolismo , Hígado Graso/microbiología , Microbioma Gastrointestinal , Intestinos/microbiología , Animales , Colesterol 7-alfa-Hidroxilasa/genética , Colesterol 7-alfa-Hidroxilasa/metabolismo , Modelos Animales de Enfermedad , Hígado Graso/enzimología , Hígado Graso/genética , Hígado Graso/metabolismo , Humanos , Mucosa Intestinal/metabolismo , Metabolismo de los Lípidos , Hígado/enzimología , Hígado/metabolismo , Masculino , Ratones , Receptores Citoplasmáticos y Nucleares/genética , Receptores Citoplasmáticos y Nucleares/metabolismo
2.
Artículo en Inglés | MEDLINE | ID: mdl-22474520

RESUMEN

We sought the long-term efficacy of traditionally used antidiabetic herbs in controlling blood glucose homeostasis and low-grade inflammation. Ninety-four subjects with either impaired glucose tolerance or mild T2D were randomized either to treatment arm or placebo arm and received 1 : 1 : 1 mixture of ginseng roots, mulberry leaf water extract, and banaba leaf water extract (6 g/d) for 24 weeks. Oral 75 g glucose tolerance test was performed to measure glucose and insulin responses. Blood biomarkers of low-grade inflammation were also determined. Results found no significant difference in glucose homeostasis control measure changes. However, plasma intracellular adhesion molecule-1 (ICAM-1) concentration was decreased showing a significant between-treatment changes (P = 0.037). The concentrations of vascular cell adhesion molecule-1 (VCAM-1) (P = 0.014) and ICAM-1 (P = 0.048) were decreased in the treatment group at week 24, and the oxidized low-density lipoprotein (ox-LDL) concentration was reduced at week 24 compared to the baseline value in the treatment group (P = 0.003). These results indicate a long-term supplementation of ginseng, mulberry leaf, and banaba leaf suppresses inflammatory responses in T2D.

3.
Int J Obes (Lond) ; 36(2): 273-80, 2012 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-21544082

RESUMEN

OBJECTIVE: Studies have indicated that obesity is associated with a higher risk of colorectal cancer. This study was performed to determine the effect of diet-induced obesity on the formation of azoxymethane (AOM)/dextran sodium sulfate (DSS)-induced colon tumors and to identify adiposity-related mechanisms. METHODS: Male A/J mice were placed on either a high-fat diet (HFD; 45% of total calories from fat) or a normal diet (ND; 15% of calories from fat) for 12 weeks. To induce colon tumors, AOM was administered at a dose of 10 mg/kg body weight, followed by two cycles of DSS supply. RESULTS: Study results indicated that the HFD group had twofold higher numbers of colonic tumors, as compared with the ND group. The HFD group also had significantly increased body weight and epididymal fat weight, which were associated with increases of serum insulin, insulin-like growth factor-1, leptin, epididymal fat pad leptin mRNA and colonic leptin receptor (Ob-R) mRNA. Animals on HFD showed higher expressions of Ob-R, insulin receptor, phosphorylated Akt, phosphorylated extracellular signal-regulated kinases, Bcl-xL and Cyclin D1 proteins in the colon. CONCLUSION: The results suggest that HFD-induced obesity facilitates colon tumor formation, possibly by regulating downstream targets of circulating adiposity-related factors via receptor-mediated signaling of the phosphatidylinositol 3-kinase/Akt pathway.


Asunto(s)
Azoximetano/farmacología , Carcinógenos/farmacología , Colitis/metabolismo , Colon/metabolismo , Neoplasias del Colon/metabolismo , Obesidad/metabolismo , Animales , Western Blotting , Colitis/inducido químicamente , Colitis/complicaciones , Colon/patología , Neoplasias del Colon/inducido químicamente , Neoplasias del Colon/patología , Dieta Alta en Grasa , Modelos Animales de Enfermedad , Masculino , Ratones , Obesidad/complicaciones , Obesidad/patología , Transducción de Señal
4.
Eur J Clin Nutr ; 64(9): 924-32, 2010 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-20571498

RESUMEN

BACKGROUND: Although high soy consumption may be associated with lower breast cancer risk in Asian populations, findings from epidemiological studies have been inconsistent. OBJECTIVE: We investigated the effects of soy intake on breast cancer risk among Korean women according to their menopausal and hormone receptor status. METHODS: We conducted a case-control study with 358 incident breast cancer patients and 360 age-matched controls with no history of malignant neoplasm. Dietary consumption of soy products was examined using a 103-item food frequency questionnaire. RESULTS: The estimated mean intakes of total soy and isoflavones from this study population were 76.5 g per day and 15.0 mg per day, respectively. Using a multivariate logistic regression model, we found a significant inverse association between soy intake and breast cancer risk, with a dose-response relationship (odds ratios (OR) (95% confidence interval (CI)) for the highest vs the lowest intake quartile: 0.36 (0.20-0.64)). When the data were stratified by menopausal status, the protective effect was observed only among postmenopausal women (OR (95% CI) for the highest vs the lowest intake quartile: 0.08 (0.03-0.22)). The association between soy and breast cancer risk did not differ according to estrogen receptor (ER)/progesterone receptor (PR) status, but the estimated intake of soy isoflavones showed an inverse association only among postmenopausal women with ER+/PR+ tumors. CONCLUSIONS: Our findings suggest that high consumption of soy might be related to lower risk of breast cancer and that the effect of soy intake could vary depending on several factors.


Asunto(s)
Neoplasias de la Mama/química , Neoplasias de la Mama/epidemiología , Isoflavonas/administración & dosificación , Receptores de Estrógenos/análisis , Receptores de Progesterona/análisis , Alimentos de Soja , Adulto , Anciano , Neoplasias de la Mama/prevención & control , Estudios de Casos y Controles , Intervalos de Confianza , Encuestas sobre Dietas , Relación Dosis-Respuesta a Droga , Femenino , Humanos , Incidencia , Corea (Geográfico)/epidemiología , Modelos Logísticos , Menopausia , Persona de Mediana Edad , Análisis Multivariante , Oportunidad Relativa , Factores de Riesgo , Encuestas y Cuestionarios
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