Project description:We examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice.
Project description:We examined the effect of oral TUDCA treatment on hepatic steatosis and associated changes in hepatic gene expression in ob/ob mice. We administered TUDCA to ob/ob mice at a dose of 500 mg/kg twice a day by gastric gavage for 3 weeks. Body weight, glucose homeostasis, endoplasmic reticulum (ER) stress, and hepatic gene expression were examined in comparison with control ob/ob mice and normal littermate C57BL/6J mice.
Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison Leptin deficient (ob/ob) mice were continuously administered leptin over 12-days using central (intracerebroventricular) or peripheral (subcutaneous) route of administration. Liver RNA was extracted and hybridized to Illumina microarrays and gene expression data was analyzed. The global gene expression profiles were compared after the central and peripheral leptin treatments in ob/ob mice and C57BL6 mice were used for the baseline gene expression.
Project description:Non-alcoholic fatty liver disease (NAFLD) is rapidly becoming the most common liver disease worldwide, yet the pathogenesis of NAFLD is only partially understood. Here, we investigated the role of the gut bacteria in NAFLD by stimulating the gut bacteria via feeding mice the fermentable dietary fiber guar gum and suppressing the gut bacteria via chronic oral administration of antibiotics. Guar gum feeding profoundly altered the gut microbiota composition, in parallel with reduced diet-induced obesity and improved glucose tolerance. Strikingly, despite reducing adipose tissue mass and inflammation, guar gum enhanced hepatic inflammation and fibrosis, concurrent with markedly elevated plasma and hepatic bile acid levels. Consistent with a role of elevated bile acids in the liver phenotype, treatment of mice with taurocholic acid stimulated hepatic inflammation and fibrosis. In contrast to guar gum, chronic oral administration of antibiotics effectively suppressed the gut bacteria, decreased portal secondary bile acid levels, and attenuated hepatic inflammation and fibrosis. Neither guar gum or antibiotics influenced plasma lipopolysaccharide levels. In conclusion, our data indicate a causal link between changes in gut microbiota and hepatic inflammation and fibrosis in a mouse model of NAFLD, possibly via alterations in bile acids.
Project description:To test whether NDGA attenuate dyslipidemia and hepatic steatosis by enhancing fatty acid oxidation through activation of PPAR-α. Using wild type (WT, C57BL/6) fed with chow diet as control, WT mice were either fed with high-fat diet or high-fat diet with NDGA (2.5g/kg food); ob/ob mice were fed with either chow or chow with NDGA (2.5 g/kg food), and maintained on the respective diets for 16 weeks. The expression of lipid metabolism related genes in the liver of these mice were analyzed using Phalanx GPL6845 platform (Mouse OneArray V1). Together with other biochemical/physiological data, our results suggest that the beneficial actions of NDGA on dyslipidemia and hepatic steatosis in ob/ob mice are exerted primarily through enhanced fatty acid oxidation and energy utilization via the activation of PPAR- α receptor activity. To examine the changes in gene expression in liver of WT and ob/ob mice with different NDGA diet treatment, RNA isolated from 3 animals of each group were used for studies of gene expression profiles. Phalanx GPL6845 platform (Mouse OneArray V1) was used for the microarrays analysis.
Project description:The purpose of this study was to identify leptin target genes and subsequent pathways correlated with leptin-mediated weight loss. We utilized the microarray technology to compare two types of leptin administration: one involving a direct stimulatory effect when administered peripherally (subcutaneous: SQ) and another that is indirect, involving a hypothalamic relay that suppresses food intake when leptin is administered centrally (intracerebroventricular: ICV). We report here the impact of central and peripheral administration of leptin on food intake, body weight and body fat composition in ob/ob mice. We also report hepatic gene expression changes caused by central versus peripheral leptin administration. Keywords: comparison
Project description:Osteoradionecrosis of the jaw (ORNJ) is a severe complication following head and neck radiotherapy that significantly impacts the quality of life of patients. Currently, there is a lack of comprehensive understanding of the microenvironmental factors involved in ORNJ. In this study, we reveal the activation of taurine metabolism in irradiated mandibular stromal cells using scRNA-Seq and demonstrate a decrease in taurine levels in irradiated bone marrow mesenchymal stromal cells (BMSCs) through metabolomics. Compared with unirradiated BMSCs, taurine uptake in irradiated BMSCs increases. Taurine concentrations in the peripheral blood and jaws of irradiated mice are significantly lower than those in unirradiated mice (P = 0.0064 and 0.0249 respectively). Supplementation with taurine promotes osteogenic differentiation, reduces oxidative stress, and decreases DNA damage in irradiated BMSCs. Oral administration of taurine significantly improves the survival rate of irradiated mice and enhances osteogenesis in irradiated jaws. Our study highlights the role of taurine in the recovery from radiation-induced jaw injury, and suggests its potential as a non-invasive therapeutic option for combating ORNJ.
Project description:We found out that bile acid pathways were deeply altered in cachectic mice bearing ectopic tumor, leading to an increase in portal and liver conjugated bile acid levels. Counteracting this increased level in conjugated bile acids using cholestyramine, a bile acid sequestrant, reduced hepatic inflammation in cachectic mice with no impact on steatosis and minor effects on thermogenesis. Hepatic whole transcriptome analysis identified 16 pathways altered in cachectic mice which were counteracted by cholestyramine, pointing out the large contribution of bile acids to hepatic disturbances occurring in cancer cachexia.
Project description:Conjugated Linoleic Acid (CLA) is a collective term for the positional and geometric isomers of linoleic acid. In recent years CLA has been reported to have anti-carcinogenic, anti-obesity, anti-inflammatory and anti-artherogenic effects. The aim of this study was to determine the effects of a natural high-CLA enriched beef source on three primary insulin responsive tissues: adipose, liver and skeletal muscle. ob/ob mice were assigned to one of two diets: a control beef diet, low in c9, t11-CLA (control diet) or a c9, t11-CLA enriched beef diet. After a 28 day feeding trial, RNA was extracted from adipose, liver and skeletal muscle tissue and hybridized to Affymetrix microarrays.
Project description:Okra (Abelmoschus esculentus (L.) Moench) serves as a botanical resource extensively utilized in ethnomedicine. Prior investigations revealed that okra polysaccharide (OP) ameliorated hepatocellular lipotoxicity in vitro context. Nonetheless, the curative efficacy and the precise molecular mechanisms implicated in metabolic-associated fatty liver disease (MAFLD) warrant further elucidation. To address this gap, two murine models of MAFLD, namely obese Ob/Ob mice and high fat/cholesterol/fructose (HFCF) fed mice, were employed. The therapeutic implications of OP supplementation were assessed through quantification of lipid specific biomarkers and hepatic histopathological examination. Complementary transcriptomic, phosphoproteomic, and in vitro analyses were conducted to decipher the molecular underpinnings. In the Ob/Ob mouse model, OP substantively mitigated both circulating and hepatic lipid concentrations, concurrently ameliorating hepatic steatosis. In the context of HFCF-induced MAFLD, OP not only attenuated hepatic lipidic sequestration but also abrogated concomitant inflammation and fibrosis. Subsequent RNA-sequencing analyses on hepatic tissues derived from HFCF-diet mice delineated that OP modulated MAFLD-associated transcriptional signatures. A synergistic assessment of transcriptomics and phosphoproteomics disclosed a salient effect of OP on the Peroxisome Proliferator-Activated Receptor (PPAR) pathway, particularly manifested by the upregulation of PPAR-γ signaling. In murine hepatocytes, OP counteracted steatosis and inflammation via the activation of PPAR-γ signaling. The effects induced by OP were nullified upon administration of the PPAR-γ-specific antagonist GW9662. Collectively, our empirical evidence furnishes the inaugural demonstration that OP mitigates MAFLD pathology through the activation of PPAR-γ signaling, thereby presenting a novel therapeutic avenue for MAFLD intervention.