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ABSTRACT:
PROVIDER: PRJNA988830 | ENA |
REPOSITORIES: ENA
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Project description:As patients with heart failure with preserved ejection fraction (HFpEF) present with multiple comorbidities, we hypothesized, that metabolic syndrome in aging animals could lead to the development of diastolic dysfunction and HFpEF. HFpEF is a common complex morbid syndrome for which there are currently little evidence-based therapies. Obesity-prone rats were exposed to high-fat diet and compared to obesity-resistant rats fed with standard chow. Phenotyping of metabolic syndrome, associated with echocardiographic and cardiac hemodynamic measurements, was performed after 4 and 12 months. Blood and myocardial tissue sampling were performed for pathobiological evaluation. High-fat diet in obesity-prone rats elicited metabolic syndrome, characterized by increased body and abdominal fat weights, glucose intolerance and hyperlipidemia, as well as increased left ventricular (LV) systolic pressure (after 12 months). This was associated with LV diastolic dysfunction (assessed by increased LV end-diastolic pressure) and pulmonary hypertension (assessed by increased right ventricular systolic pressure). Echocardiography revealed significant concentric LV hypertrophy, while LV ejection fraction was preserved. LV remodeling was associated with cardiomyocyte hypertrophy, as well as myocardial and perivascular fibrosis. Circulating levels of soluble ST2 markedly increased in rats with HFpEF, while plasma NT-proBNP levels decreased. RNA-sequencing analysis identified clusters of genes implicated in fatty acid metabolism and calcium-dependent contraction as upregulated pathways in the myocardium of rats with HFpEF. High-fat diet during 12 months in obesity-prone rats led to the development of a relevant preclinical model of HFpEF with multiple comorbidities, suitable for investigating novel therapeutic interventions.
2022-02-02 | GSE189190 | GEO
Project description:The metabolic syndrome represents a cluster of well-documented risk factors for the development of type 2 diabetes and cardiovascular disease. Next to visceral obesity, dyslipidemia and insulin resistance, excessive triglyceride accumulation in the liver has been implicated to play a role in the development of the metabolic syndrome. To investigate the underlying molecular changes leading to hepatic steatosis we performed microarray analysis on livers of mice either fasted over night or fed a high fat diet for 2 Weeks. We analysed 7 500 genes and subsequently performed a pathway analysis to identify changes in hepatic genes in both models. Fasting induced a high number of differentially expressed hepatic genes, resulting in an change towards an energy saving phenotype. In contrast only a small number of genes were differentially expressed after high fat diet. Fasting promoted gluconeogenesis and b-oxidation, strongly suppressed cholesterol synthesis and activated pathways to preserve hepatic function. High fat diet induced steatosis was accompanied by the activation of the stearoyl-CoA desaturase and the lipogenic transcription factor Srebp-1c, both implicated in the development of hepatic insulin resistance. These changes reflect the activation of different gene expression programs in response to plasma lipid overload. Keywords: Diet intervention Two conditions, fasting and high fat diet. 5 biological replicates for comparison of high fat diet versus fasting and controls versus high fat diet, 4 biological replicates for the comparison of controls versus fasting. All biological replicates are performed as technical replicates in the form of a dye-swap. Total number of arrays hybridises is therefore 28.
2011-04-02 | E-GEOD-8576 | biostudies-arrayexpress
Project description:Insulin resistance drives the development of type 2 diabetes (T2D). In liver, diacylglycerol (DAG) is a key mediator of lipid-induced insulin resistance. DAG activates protein kinase C epsilon (PKCε), which phosphorylates and inhibits the insulin receptor. In rats, a 3-day high fat diet produces hepatic insulin resistance through this mechanism, and knockdown of hepatic PKCε protects against high fat diet-induced hepatic insulin resistance. Here we employ a systems level approach to uncover additional signaling pathways involved in high fat diet-induced hepatic insulin resistance. We used quantitative phosphoproteomics to map global in vivo changes in hepatic protein phosphorylation in chow-fed, high fat-fed, and high fat-fed with PKCε knockdown rats to distinguish the impact of lipid- and PKCε-induced protein phosphorylation.
2018-08-30 | PXD010209 | Pride
Project description:Exploration of new markers that define impaired metabolic flexibility using an acute postprandial challenge test. Healthy subjects underwent a 4-week high-fat high-calorie diet. High-fat challenges were performed in these subjects before and after the diet and in subjects with the metabolic syndrome.
2020-01-01 | GSE124534 | GEO
Project description:According to different feeding and treatment conditions, 36 C57BL/6JC rats were randomly divided into normal diet group (WC group), high fat diet group (WF group) and high fat diet + silibinin group (WS group). TMT combined with LC-MS/MS were used to study the expression of WAT in epididymis of HFD-induced obese rats and normal diet rats. Gene Ontology, InterPro and KEGG databases were used to analyze the cellular processes, the biological processes, the corresponding molecular functions and the network molecular mechanisms involved
2020-01-13 | PXD016635 | Pride
Project description:In this study, we assessed the effect of acute oral administration of ellagic acid on metabolic parameters, oxidative stress and transcriptomic profiles in an inbred rodent model, carrying a variant of one of the metabolic syndrome-related genes, Zbtb16 (Zinc Finger And BTB Domain Containing 16). Over a period of three weeks, adult male rats of the SHR-Lx/k.o. strain were fed a high-fat diet accompanied with daily intragastric gavage of ellagic acid (50 mg/kg body weight; HFD-EA rats) or solvent only (HFD rats). At the end of the protocol, morphometric and metabolic parameters, including glucose tolerance test, serum lipid concentration and oxidative stress markers along with transcriptomic profile of liver, brown, and epididymal adipose tissues were assessed.
2021-02-19 | E-MTAB-8928 | biostudies-arrayexpress
Project description:Potential mechanism was discovered through expression profiling of a total of 3545 miRNAs in liver of rats fed with high fat diet after HTG treatment. MiRNAs in liver of rats(3 group, normal fat diet group, 3, high fat diet group, 3, high fat diet + HTG treatment, 3) were detected, and differentially expressed miRNAs were analyzed to reveal potential mechanism of HTG in treating dyslipidaemia.
2023-11-21 | GSE241806 | GEO
Project description:We studied the effect of dietary fat type, varying in polyunsaturated/saturated fatty acid ratio's (P/S) on development of metabolic syndrome. C57Bl/6J mice were fed purified high-fat diets (45E% fat) containing palm oil (HF-PO; P/S 0.4), olive oil (HF-OO; P/S 1.1) or safflower oil (HF-SO; P/S 7.8) for 8 weeks. A low-fat palm oil diet (LF-PO; 10E% fat) was used as a reference. Additionally, we analyzed diet-induced changes in gut microbiota composition and mucosal gene expression. The HF-PO diet induced a higher body weight gain and liver triglyceride content compared to the HF-OO, HF-SO or LF-PO diet. In the intestine, the HF-PO diet reduced microbial diversity and increased the Firmicutes/Bacteroidetes ratio. Although this fits a typical obesity profile, our data clearly indicate that an overflow of the HF-PO diet to the distal intestine, rather than obesity itself, is the main trigger for these gut microbiota changes. A HF-PO diet-induced elevation of lipid metabolism-related genes in the distal small intestine confirmed the overflow of palm oil to the distal intestine. Some of these lipid metabolism-related genes were previously already associated with the metabolic syndrome. In conclusion, our data indicate that saturated fat (HF-PO) has a more stimulatory effect on weight gain and hepatic lipid accumulation than unsaturated fat (HF-OO and HF-SO). The overflow of fat to the distal intestine on the HF-PO diet induced changes in gut microbiota composition and mucosal gene expression. We speculate that both are directly or indirectly contributive to the saturated fat-induced development of obesity and hepatic steatosis. Keywords: Diet intervention study Nine-week-old C57Bl/6J mice were fed a low-fat diet (LF-PO) and three different types of high-fat diet, based on palm oil (HF-PO; P/S1.0), olive oil (HF-OO; P/S4.6) and safflower oil (HF-SO; P/S10.1) for 8 weeks. Body weight was recorded weekly and after 7 weeks of diet intervention an oral glucose tolerance test was performed. After 2 weeks of diet intervention, 6 mice per high-fat diet group were anaesthetized with a mixture of isofluorane (1.5%), nitrous oxide (70%) and oxygen (30%) and the small intestines were excised. Adhering fat and pancreatic tissue were carefully removed. The small intestines were divided in three equal parts along the proximal to distal axis (SI 1, SI 2 and SI 3) and microarray analysis was performed on mucosal scrapings.
2012-06-17 | E-GEOD-18586 | biostudies-arrayexpress
Project description:High sugar consumption, as well as high-fat diet, is a known cause of obesity and metabolic syndrome. However, the synergistic effect of high-sugar and high-fat consumption rarely has been evaluated, especially in terms of transcriptional regulation. Therefore, we focused on the effect of high sugar consumption on hepatic transcriptional networks in normal and high fat-fed mice. C57BL/6J mice were divided into four groups and were provided either 23%(w/v) sugar solution or plain water with either high-fat or normal-fat diet for 10 weeks. As a result, high sugar consumption significantly altered lipid metabolism-related genes in normal fat-fed mice; however, in high fat-fed mice, high sugar consumption altered inflammation-responsive genes rather than lipid metabolism. After all, these modulations eventually increased lipid accumulation in the liver and caused systemic metabolic disturbances. These observations for the first time suggested that high sugar consumption along with high-fat diet could lead to the development of severe metabolic syndrome via altering hepatic transcriptional networks.
2017-01-01 | GSE70477 | GEO