The metabolic response to a high-fat diet reveals obesity-prone and -resistant phenotypes in mice with distinct mRNA-seq transcriptome profiles
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ABSTRACT:
ORGANISM(S): Mus musculus
PROVIDER: GSE74804 | GEO | 2017/11/08
SECONDARY ACCESSION(S): PRJNA301586
REPOSITORIES: GEO
Similar Datasets
Project description:Rodents respond to chronic high fat diet in at least two ways: some of them may readily gain body weight and become obese (termed obesity-prone), and others may not (termed obesity-resistant). An integrated approach of transcript and metabolic profiling of obesity-prone and obesity-resistant rats has been conducted, showing significantly different transcript and metabolic profiles in the two phenotypes. The major transcriptional differences involved hepatic fatty acid metabolism and ketogenesis in response to 16 weeks of high fat diet. At the same time, the different metabolic profiles (in liver tissue extracts, serum, and urine) between the two phenotypes could be ascribed to the corresponding pathways identified with multivariate statistical analysis, including fatty acid metabolism, Krebs cycle, and amino acid metabolism. The integration of results from both transcript and metabolic profiling revealed the different responses to dietary intervention of the two phenotypes and the physiological basis of susceptibility to metabolic disease in obesity-prone rats from a systematic view.
2008-05-20 | GSE11492 | GEO
Project description:An 8-week high fat palm oil diet causes obesity and insulin resistance in C57BL/6J mice, but induces only small changes in the muscle transcriptome. Introduction: The metabolic syndrome (MS) is a cluster of metabolic abnormalities linked to an increased risk of type 2 diabetes and cardiovascular diseases. Two major characteristics of the MS are obesity and insulin resistance. In the present study we investigated the effect of obesity and insulin resistance on the mouse muscle transcriptome. Methods: C57BL/6J mice were fed a palm oil-based low fat diet (LFD) or high fat diet (HFD) for eight weeks. Microarray analysis was performed by using two complementary strategies: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. Results: HFD mice develop obesity and whole-body insulin resistance. Despite these metabolic disturbances we found that HFD induces relatively small changes in gene expression (< 1.3 fold). Only the up-regulation of FA oxidation and the down-regulation of the MAPK cascade were specific for the HFD intervention. Eight-weeks of aging induced more changed gene expression levels than the HFD, including genes involved in cell-cell interaction and development. Conclusion: Eight weeks of aging induce more pronounced changes in the muscle transcriptome than an HFD. Since only one strategy revealed the transcriptional down-regulation of the MAPK cascade, whereas both strategies showed the up-regulation of FA oxidation we suggest the use of complementary analysis strategies by the genome-wide search of gene expression changes induced by mild interventions, such as an HFD. Keywords: diet intervention and time course In this study, C57BL/6J mice were fed a high fat (HF) diet for 8 weeks to induce obesity and insulin resistance. Plasma levels of the adipokines leptin and adiponectin were measured. To investigate how these metabolic disturbances will influence the skeletal muscle transcriptome we performed whole-genome microarray analysis. Functional implications were assessed by analyses of predefined gene sets based on Gene Ontology, biochemical, metabolic and signaling pathways.
2010-08-10 | E-GEOD-17576 | biostudies-arrayexpress
Project description:Objective Recent evidence indicates that the adult hematopoietic system is susceptible to diet-induced lineage skewing. It is not known whether the developing hematopoietic system is subject to metabolic programming via in utero high fat diet (HFD) exposure, an established mechanism of adult disease in several organ systems. We previously reported substantial losses in offspring liver size with prenatal HFD. As the liver is the main hematopoietic organ in the fetus, we asked whether the developmental expansion of the hematopoietic stem and progenitor cell (HSPC) pool is compromised by prenatal HFD and/or maternal obesity. Methods We used quantitative assays, progenitor colony formation, flow cytometry, transplantation, and gene expression assays with a series of dietary manipulations to test the effects of gestational high fat diet and maternal obesity on the day 14.5 fetal liver hematopoietic system. Results Maternal obesity, particularly when paired with gestational HFD, restricts physiological expansion of fetal HSPCs while promoting the opposing cell fate of differentiation. Importantly, these effects are only partially ameliorated by gestational dietary adjustments for obese dams. Competitive transplantation reveals compromised repopulation and myeloid-biased differentiation of HFD-programmed HSPCs to be a niche-dependent defect, apparent in HFD-conditioned male recipients. Fetal HSPC deficiencies coincide with perturbations in genes regulating metabolism, immune and inflammatory processes, and stress response, along with downregulation of genes critical for hematopoietic stem cell self-renewal and activation of pathways regulating cell migration. Conclusions Our data reveal a previously unrecognized susceptibility to nutritional and metabolic developmental programming in the fetal HSPC compartment, which is a partially reversible and microenvironment-dependent defect perturbing stem and progenitor cell expansion and hematopoietic lineage commitment. Examination of differentially expressed genes between gestational day 15 (+/- 0.5 days) C57BL/6 mouse fetal livers from diet-induced (60% fat diet) obese or control female mice.
2014-10-25 | E-GEOD-62715 | biostudies-arrayexpress
Project description:An 8-week high fat palm oil diet causes obesity and insulin resistance in C57BL/6J mice, but induces only small changes in the muscle transcriptome. Introduction: The metabolic syndrome (MS) is a cluster of metabolic abnormalities linked to an increased risk of type 2 diabetes and cardiovascular diseases. Two major characteristics of the MS are obesity and insulin resistance. In the present study we investigated the effect of obesity and insulin resistance on the mouse muscle transcriptome. Methods: C57BL/6J mice were fed a palm oil-based low fat diet (LFD) or high fat diet (HFD) for eight weeks. Microarray analysis was performed by using two complementary strategies: (1) 8-week HFD transcriptome versus 8-week LFD transcriptome and (2) transcriptome of mice sacrificed at the start of the intervention versus 8-week LFD transcriptome and 8-week HFD transcriptome, respectively. Results: HFD mice develop obesity and whole-body insulin resistance. Despite these metabolic disturbances we found that HFD induces relatively small changes in gene expression (< 1.3 fold). Only the up-regulation of FA oxidation and the down-regulation of the MAPK cascade were specific for the HFD intervention. Eight-weeks of aging induced more changed gene expression levels than the HFD, including genes involved in cell-cell interaction and development. Conclusion: Eight weeks of aging induce more pronounced changes in the muscle transcriptome than an HFD. Since only one strategy revealed the transcriptional down-regulation of the MAPK cascade, whereas both strategies showed the up-regulation of FA oxidation we suggest the use of complementary analysis strategies by the genome-wide search of gene expression changes induced by mild interventions, such as an HFD. Keywords: diet intervention and time course
2010-08-10 | GSE17576 | GEO
Project description:There is an increasing clinical evidence that obesity exerts deleterious effects on the skeleton. While obesity coexists with estrogen deficiency in postmenopausal women, their combined effects on the skeleton are poorly studied. Thus, we investigated the impact of high-fat diet (HFD) on bone and metabolism of ovariectomized (OVX) female mice (C57BL/6J). OVX or sham operated mice were fed either HFD (60%fat) or normal diet (ND) (10%fat) for 12 weeks. HFD-OVX group exhibited pronounced increase in body weight (~86% in HFD and ~122% in HFD-OVX, p<0.0005) and impaired glucose tolerance. Bone microCT-scanning revealed a pronounced decrease in trabecular bone volume/total volume (BV/TV) in HFD-OVX (15.6±0.48% in HFD and 37.5±0.235% in HFD-OVX, p<0.005) and expansion of bone marrow adipose tissue (BMAT) (+60.7±9.9% in HFD vs +79.5±5.86% in HFD-OVX, p<0.005). Mechanistically, HFD-OVX treatment led to upregulation of genes markers of senescence, bone resorption, adipogenesis and inflammation and downregulation of gene markers of bone formation and bone development. Similarly, HFD- OVX treatment resulted in significant changes in bone tissue levels of Purine/Pyrimidine and Glutamate metabolisms, known to play a regulatory role in bone metabolism. Obesity and estrogen deficiency exert combined deleterious effects on bone resulting in accelerated cellular senescence, expansion of BMAT and impaired bone formation leading to decreased bone mass. Our results suggest that obesity may increase bone fragility in post-menopausal women.
2022-12-05 | GSE194075 | GEO
Project description:Background Breakthroughs in HIV treatment, especially antiretroviral therapy (ART), have massively reduced mortality. However, ART-treated individuals display elevated rates of obesity, diabetes, and cardiovascular disease, collectively known as metabolic syndrome. These co-morbidities represent a considerable threat to long-term survival and quality of life. Previous studies have shown that high-fat feeding induces persistent low-grade systemic and adipose tissue inflammation contributing to insulin resistance and metabolic dysregulation via adipose-infiltrating macrophages. Methods and Results Studies herein test the hypothesis that ART potentiates the inflammatory effects of a high-fat diet (HFD). C57Bl/6J mice on a HFD or standard chow containing ART or vehicle, were subjected to functional metabolic testing, RNA-sequencing of epididymal white adipose tissue (eWAT), and array-based kinomic analysis of eWAT-infiltrating macrophages. ART-treated mice on a HFD displayed fat mass accumulation, impaired glucose tolerance, and potentiated insulin resistance. Gene set enrichment and kinomic array analyses revealed a pro-inflammatory transcriptional signature depicting granulocyte migration and activation. Conclusions The current study reveals a HFD-ART interaction that increases inflammatory transcriptional pathways in eWAT consistent with macrophage infiltration, resulting in impaired glucose metabolism, energy balance, and metabolic dysfunction.
2018-09-14 | GSE110035 | GEO
Project description:The expression profiles of lncRNAs in BAT were investigated by high-throughput RNA sequencing using HFD-induced C57BL/6J mice. Genes that play roles in thermogenesis and related pathways were identified.
2022-07-09 | GSE207064 | GEO
Project description:Several aspects common to a Western lifestyle, including obesity and decreased physical activity, are known risks for gastrointestinal cancers. There is an increasing amount of evidence suggesting that diet profoundly affects the composition of the intestinal microbiota. Moreover, there is now unequivocal evidence linking a dysbiotic gut to cancer development. Yet, the mechanisms through which high-fat diet (HFD)-mediated changes in the microbial community impact the severity of tumorigenesis in the gut, remain to be determined. Here we demonstrate that HFD promotes tumor progression in the small intestine of genetically susceptible K-rasG12Dint mice independent of obesity. HFD consumption in conjunction with K-Ras mutation mediates a shift in the composition of gut microbiota, which is associated with a decrease in Paneth cell antimicrobial host defense that compromises dendritic cell (DC) recruitment and MHC-II presentation in the gut-associated lymphoid tissues (GALTs). DC recruitment in GALTs can be normalized, and tumor progression attenuated completely, when K-rasG12Dint mice are supplemented with the short-chain fatty acid butyrate, a bacterial fermentation endproduct. Importantly, Myd88-deficiency completely blocks tumor progression in K-rasG12Dint mice. Transfer of fecal samples from diseased donors into healthy adult K-rasG12Dint mice is sufficient to transmit disease in the absence of HFD. Furthermore, treatment with antibiotics completely blocks HFD-induced tumor progression, suggesting a pivotal role for distinct microbial shifts in aggravating disease in the small intestine. Collectively, these data underscore the importance of the reciprocal interaction between host and environmental factors in selecting intestinal microbiota that favor carcinogenesis, and suggest tumorigenesis may be transmissible among genetically predisposed individuals. 3 mice each for each treatment.
2014-03-28 | E-GEOD-56257 | biostudies-arrayexpress
Project description:Mice were fed for 2, 10 or 30 days with a normal chow (NC) or a high fat diet (HFD). At each time point, mice were sacrificed and liver samples were collected and immediately frozen in liquid nitrogen. Total RNA from each sample was further extracted, purified, quality-controled before and after amplification. Cy3-labeled RNA from individual liver sample was co-hybridized with a Cy5-labeled pool of RNA on the mouse 17K microarray. Keywords: diet response, time course, mouse strains For a given time point, each individual RNA sample was hybridized with a pool of RNA from 6 mice
2009-08-09 | E-GEOD-12409 | biostudies-arrayexpress
Project description:Effects of EPA/DHA enriched high fat diets (HFD) compared to HFD-Corn oil after 8 weeks intervention on age/obesity induced skeletal muscle degradation. Results provides novel information on the signalling pathways regulated by EPA and DHA enriched HFD in delaying the onset of muscle degradation in C57Bl/6J mice compared with HFD-Corn oil.
2016-05-31 | GSE76361 | GEO