Project description:To make the human liver accessible to metabolic treatments, we employed a liver-specific humanized mouse model in which approximately 50% of the mouse hepatocytes were replaced by human ones. To capture transcriptomes reflecting pathophysiology and therapeutic development of metabolic diseases, we subjected the humanized mice to dietary intervention and the key metabolic transcriptional factor agonist treatments. We then performed rna exoression profiling analysis using data obtained from nanopore direct RNA sequencing of these humanized mice.
2024-01-23 | GSE224278 | GEO
Project description:Individualized responses of gut microbiota to dietary intervention modeled in humanized mice
Project description:The aim of this study was to investigate if milk fat globule membrane (MFGM) enclosing the dairy fat influence peripheral blood mononuclear cells (PBMC) gene expression. This study was a 8-week single-blind, randomized, controlled isocaloric trial with two parallel groups including overweight (mean BMI: 28) adult women (n=30). All subjects consumed 40 g dairy fat per day either as cream (MFGM diet) or as butter oil (control diet). MFGM diet and control diet showed differential responses in plasma cholesterol. Absolute differences in gene expression were calculated for each gene in each subject, comparing after with before the intervention. These absolute differences in gene expression were compared between intervention groups with T-test and with Significance Analysis of Microarrays (SAM). 19 genes were significantly different regulated by the two diets with a FDR of 23%. Most of thechanges in gene expression correlated with changes in blood lipids. Patients were examined in the morning after 12 h's fasting. Whole blood was obtained before (W0) and after completion (W8) of the dietary intervention for isolation of PBMCs and RNA extraction. From total RNA we prepared and hybridised biotinylated complementary RNA to GeneChip Human Gene 1.1 ST Arrays (Affymetrix Inc., Santa Clara, CA), and then washed, stained and scanned the slides using standardised protocols (Affymetrix Inc.). Signicance analysis of microarrays (SAM) was use to compare the difference in gene expression between groups.
Project description:To make the human liver accessible to metabolic treatments, we employed a liver-specific humanized mouse model in which approximately 50% of the mouse hepatocytes were replaced by human ones. For the dietary treatment, the humanized mice were allowed free access to food (AL, n=4 for donor1, n=3 for donor2) or subjected to a twenty-four hours food withdrawal (Fast, n=4 for donor1, n=3 for donor2). For the transcription factor agonist treatments, the humanized mice were injected with DMSO (n=4), fenofibrate (n=4, 50mg/kg, Sigma-Aldrich, Cat. F6020), rosiglitazone (n=4,10mg/kg, Sigma-Aldrich, Cat. R2408) and GW4064 (n=4, 30mg/kg, Sigma-Aldrich, Cat. G5172) by i.p. injection. The livers were collected after 6 hours fasting and stored in liquid nitrogen immediately after mice sacrificed.
Project description:Recent studies have shown that FGF21 is a common target for dietary polyphenol intervention and nutritional restriction. FGF21 is also a newly recognized target of GLP-1R agonists (GLP-1RAs). Here we ask whether hepatic FGF21 is required for dietary polyphenols in exerting their metabolic beneficial effects. Liver-specific FGF21 null mice (lFgf21-/-) were utilized in current study. We found that on chow diet, no appreciable defect on glucose disposal was observed in male or female lFgf21-/- mice, while fat tolerance was impaired in male but not female lFgf21-/- mice, associated with elevated serum TG level, reduced hepatic expression of Ehhadh and Ppargc1. On high-fat-high-fructose (HFHF) diet challenge, Fgf21fl/fl mice but not lFgf21-/- mice exhibited response to curcumin intervention on reducing body weight and serum TG, and on improving fat tolerance. Resveratrol intervention also affected hepatic FGF21 expression and its downstream effectors. Metabolic beneficial effects of resveratrol intervention observed in HFHF diet challenged Fgf21fl/fl mice were either absent or attenuated in lFgf21-/- mice. Thus, hepatic FGF21 is required for curcumin and resveratrol in exerting their metabolic beneficial effect. Recognition that FGF21 is the common target of GLP-1RAs and dietary intervention brings us a novel angle in studying metabolic disease treatment and prevention.
Project description:We assessed the effect of dietary glycemic load on miRNA expression in a sample of healthy, premenopausal women participating in a 12 month intervention designed to lower dietary glycemic load. Comparing post-intervention to baseline miRNA expression data of 14 participants receiving the active intervention.
Project description:The effect of dietary calcium and dairy proteins on adipose tissue gene expression profile in diet induced obesity Keywords: disease state analysis