Characterization of Slfn3KO mice
Ontology highlight
ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE132268 | GEO | 2019/06/24
REPOSITORIES: GEO
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Project description:<p>Cd248 has recently been associated with adipose tissue physiology, demonstrated by reduced weight gain in high fat diet-fed mice with genetic deletion of Cd248 relative to controls. Here we set out to determine the metabolic consequences of loss of Cd248. Strikingly, we find these to be sex specific; By subjecting Cd248-/- and Cd248+/+ mice to a high fat diet and indirect calorimetry study, we identified that only male Cd248-/- mice show reduced weight gain compared to littermate control wildtype mice. In addition, male (but not female) mice showed a lower respiratory exchange ratio on both chow and high fat diets, indicating a predisposition to metabolise lipid. Lipidomic studies on specific fat depots found reduced triglyceride and diglyceride deposition in male Cd248-/- mice, and this was supported by reduced expression of lipogenic and adipogenic genes. Finally, metabolomic analysis of isolated, differentiated preadipocytes found alterations in metabolic pathways associated with lipid deposition in cells isolated from male, but not female, Cd248-/- mice. Overall, our results highlight the importance of sex controls in animal studies and point to a role for Cd248 in sex- and depot-specific regulation of lipid metabolism.</p>
2023-01-05 | MTBLS6615 | MetaboLights
Project description:Maternal nutrition during embryonic development and lactation influences multiple aspects of offspring health. Using mice, this study investigates the effects of maternal caloric restriction (CR) during mid-gestation and lactation on offspring neonatal development and on adult metabolic function when challenged by a high fat diet (HFD). The CR maternal model produced male and female offspring that were significantly smaller, in terms of weight and length, and females had delayed puberty. Adult offspring born to CR dams had a sexually dimorphic response to the high fat diet. Compared to offspring of maternal control dams, adult female, but not male, CR offspring gained more weight in response to high fat diet at 10 weeks. In adipose tissue of male HFD offspring, maternal undernutrition resulted in blunted expression of genes associated with weight gain and increased expression of genes that protect against weight gain. Regardless of maternal nutrition status, HFD male offspring showed increased expression of genes associated with nonalcoholic liver disease (NAFLD). Furthermore, we observed significant, sexually dimorphic differences in serum TSH. These data reveal tissue- and sex-specific changes in gene and hormone regulation following mild maternal undernutrition, which may offer protection against diet induced weight gain in adult male offspring.
2024-01-04 | GSE247985 | GEO
Project description:This pilot research trial studies the effects of chemotherapy on intestinal bacteria/organisms (microbiota) in patients newly diagnosed with breast cancer. Change in intestinal microbiota may be associated with weight gain in patients treated with chemotherapy. Weight gain has been also associated with cancer recurrence. Examining the types and quantity of bacterial composition in the stool of breast cancer patients treated with chemotherapy may help determine whether body weight and composition are associated with changes in the intestinal microbiota and allow doctors to plan better treatment to prevent weight gain and possibly disease recurrence.
| 2184354 | ecrin-mdr-crc
Project description:Background: Intestine epithelial hypoxia-inducible factor-1α (HIF-1α) plays a critical role in maintaining gut barrier function. The aim of this study was to determine genetic activation of intestinal HIF-1α ameliorates western diet-induced metabolic dysfunction–associated steatotic liver disease (MASLD). Methods: Male and/or female intestinal epithelial-specific Hif1α overexpression mice (Hif1α LSL/LSL;VilERcre) and wild-type littermates (Hif1α LSL/LSL) were fed with regular chow diet, high fructose (HFr) or high-fat (60% Kcal) high-fructose diet (HFHFr) for 8 weeks. Metabolic phenotypes were profiled. Results: Male Hif1α LSL/LSL;VilERcre mice exhibited markedly improved glucose tolerance compared to Hif1α LSL/LSL mice in response to HFr diet. Eight weeks HFHFr feeding led to obesity in both Hif1α LSL/LSL;VilERcre and Hif1α LSL/LSL mice. However, male Hif1α LSL/LSL;VilERcre mice exhibited markedly attenuated hepatic steatosis along with reduced liver size and liver weight compared to male Hif1α LSL/LSL mice. Moreover, HFHFr-induced systemic inflammatory responses were mitigated in male Hif1α LSL/LSL;VilERcre mice compared to male Hif1α LSL/LSL mice and those responses were not evident in female mice. Ileum RNA-seq analysis revealed that glycolysis/gluconeogenesis was up in male Hif1α LSL/LSL;VilERcre mice accompanied by increased epithelial cell proliferation. Conclusion: Our data provide evidence that genetic activation of intestinal HIF-1α markedly ameliorates western diet-induced MASLD in a sex-dependent manner. The underlying mechanism is likely attributed to HIF-1α activation induced upregulation of glycolysis, which, in turn, leading to enhanced epithelial cell proliferation and augmented gut barrier function.
2024-10-26 | GSE280362 | GEO
Project description:The goal of the present study was to determine whether loss of the insulin receptor alters the molecular landscape of the intestinal mucosa, using intestinal-epithelial insulin receptor knockout (IE-irKO) mice and both genetic (IRfl/fl and Villin-cre) controls. Quantitative proteomic analysis by Liquid Chromatography Mass Spectrometry (LC-MS) was deployed on jejunal and colonic mucosa from mice fed a chow- or Western diet (WD). Jejunal mucosa from IE-irKO mice demonstrated alterations in all intestinal cell linages, Paneth, goblet, absorptive and enteroendocrine cells, whereas only goblet and absorptive cells were affected in the colon. There was also a significant effect of the WD on the gut proteome. A significant reduction was detected in Paneth cell proteins with anti-microbial activity, including lysozyme C-1, angiogenin-4, cryptdin-related sequence1C-3 and -2, a-defensin 17 and intelectin-1a. The key protein expressed by goblet cells, mucin-2, was also reduced in the IE-irKO mice. Proteins involved in lipid metabolism, including aldose reductase-related protein 1, 15-hydroxyprostaglandin dehydrogenase [NAD(+)], apolipoprotein A-II and pyruvate dehydrogenase kinase isozyme 4, were increased in the mucosa of WD-fed IE-irKO mice as compared to controls. In contrast, expression of the nutrient-responsive gut hormones, glucose-dependent insulinotropic polypeptide and neurotensin, was reduced in the jejunal mucosa of IE-irKO mice, and there was a reduction in proteins of the P-type ATPases and the solute carrier-transporter family in the colon of WD-fed IE-irKO mice. In conclusion, IE-irKO mice display a distinct molecular phenotype, suggesting a biological role of insulin and its receptor in determining differentiated cell-specificity in the intestinal epithelium.
2017-08-18 | PXD005932 | Pride
Project description:Background. Food can affect the microbial balance in the human intestine, and the ingestion of probiotics may play a role in the current obesity pandemic. The objective of our study was to determine if increased Lactobacillus spp. in the intestinal microflora of mice can promote growth and if changes in the intestinal microflora are associated with modifications in metabolism. Methodology. Female BALBc mice were divided between one control and two experimental groups and inoculated either once or twice with 4×1010 Lactobacillus per animal in PBS or with PBS alone. Fecal samples were collected and tested using qPCR to detect and quantify Lactobacillus spp., Bacteroidetes and Firmicutes. Gene expression by microarray and RT-PCR was studied in liver and adipose tissue. Finally, metabolic parameters in the plasma were tested. Principal Findings. In three independent experiments, we observed an increase in both weight gain and liver weight in mice inoculated with 4×1010 Lactobacillus. Inoculation with Lactobacillus sp. (ostrich) increased the Lactobacillus spp. and Firmicutes DNA copy number in feces. The transcriptional profile of liver tissue from mice inoculated with Lactobacillus sp. (ostrich) was enriched for Gene Ontology terms related to the immune response and metabolic modifications. The mRNA levels of fatty acyl synthase (Fas), sterol regulatory element binding factor 1 (Srebp1c), tumor necrosis factor alpha (Tnf), cytochrome P450 2E1 (Cyp2e1) and 3-phosphoinositide-dependent protein kinase-1 (Pdpk1) were significantly elevated in liver tissue in experimental group animals. In gonadal adipose tissue, the expression of leptin, peroxisome proliferator-activated receptor gamma (Pparg and Srebp1c was significantly higher in experimental group animals, whereas the expression of adiponectin was significantly lower. Conclusions. Alterations in the intestinal microbiota resulted in increased weight gain. Furthermore, increased Lactobacillus spp. in the intestinal microflora of mice inoculated with Lactobacillus sp. (ostrich) resulted in accelerated weight gain, liver enlargement and metabolic changes in the plasma, liver and adipose tissue.
2010-09-21 | GSE24219 | GEO
Project description:Background and Aims - Bile acids (BAs) aid intestinal fat absorption and exert systemic actions by receptor-mediated signaling. BA receptors have been identified as drug targets for human diseases, but differences in BA metabolism between humans and mice hamper translation of pre-clinical outcomes. Cyp2c70-ablation in mice prevents synthesis of mouse/rat-specific muricholic acids (MCAs), but potential (patho)physiological consequences of their absence are unknown. We therefore assessed age- and gender-dependent effects of Cyp2c70-deficiency in mice. Methods - BA-related parameters, hepatic and intestinal gene expression patterns, liver morphology and intestinal barrier function were assessed in male and female Cyp2c70-/- mice and WT controls at different ages. Effects of ursodeoxycholic acid (UDCA) treatment were evaluated in young adult female mice. Results – Cyp2c70-/- mice were completely devoid of MCAs and showed high abundances of chenodeoxycholic and lithocholic acids. BA pool size was unaffected in young-adult male but reduced by 40% in female Cyp2c70-/- mice. Interestingly, plasma BAs and transaminases were highest in Cyp2c70-/- mice at weaning and spontaneously decreased with age. Although bile flow and biliary BA secretion were unchanged in young-adult Cyp2c70-/- mice, indicating absence of cholestasis, plasma BA and transaminase levels were still elevated. These young-adult Cyp2c70-/- mice displayed cholangiocyte proliferation, mild portal fibrosis, altered microbiome composition and increased gut permeability. Only the female Cyp2c70-/- mice developed bridging fibrosis with age (7-8 months). UDCA treatment normalized hepatic and intestinal functions and fully restored liver morphology in female Cyp2c70-/- mice. Conclusion – Cyp2c70-/- mice show transient neonatal cholestasis and develop cholangiopathic features which progress to bridging fibrosis in female mice only. These consequences of Cyp2c70-deficiency are fully restored by treatment with UDCA.
2020-12-22 | GSE138779 | GEO
Project description:It is well recognized that men and women differ in circulating lipid profiles and consequently coronary artery disease (CAD). While sex hormones like estrogens are thought to protect women from CAD risk by promoting protective lipid profiles, hormone replacement therapy in women paradoxically increases CAD risk. Biological sex is determined by both sex chromosomes and sex hormones. We used mouse models to separate effects of sex chromosomes and hormones on atherosclerosis, circulating lipids and intestinal fat metabolism. We found that an XX sex chromosome complement increases food intake, body weight, fat absorption, serum lipid concentrations and atherosclerosis in gonadal male and female mice, indicating a primary effect of sex chromosome complement. Small intestine expression of enzymes involved in lipid absorption and chylomicron assembly were increased in XX male and female mice with elevated intestinal lipids. These results reveal that an XX sex chromosome complement promotes the absorption and bioavailability of dietary fat to accelerate the development of atherosclerosis.
2019-04-17 | GSE119497 | GEO
Project description:Simple Markov model.
There are 3 disease states: Healthy, Sick, and Dead, where the Dead state is terminal.
The yearly transition probabilities are:
Healthy to Dead: 0.01; Healthy to Sick: 0.2 for Male and 0.1 for Female; Sick to Healthy: 0.1; Sick to Dead: 0.3.
The transition probability now depends on the cohort (Male or Female) and can be expressed as a function of a Boolean covariate Male.
Initial conditions: Healthy = (50 Male, 50 Female), Sick = (0,0) and Dead = (0,0).
Output: Number of men and women in each disease state for years 1-10.
2019-01-30 | MODEL1803120004 | BioModels
Project description:RNA-sequening of livers from male and female C57BL/6J mice fed either chow diet or chow diet + simvastatin (0.1g/kg body weight) for 4 weeks.
2024-02-01 | GSE184588 | GEO