Fat body-specific reduction of CTPS alleviates HFD-induced obesity
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PROVIDER: PRJNA915400 | ENA |
REPOSITORIES: ENA
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Project description:High-fat diet (HFD)-induced obesity is a multi-factorial disease including genetic, physiological, behavioral, and environmental components. Drosophila has emerged as an effective metabolic disease model. Cytidine 5'-triphosphate synthase (CTPS) is a crucial enzyme for the de novo synthesis of CTP, governing the cellular level of CTP and phospholipid synthesis. CTPS has been found to form filaments known as cytoophidia, which are evolutionarily conserved in bacteria, archaea, and eukaryotes. Here, we show that CTPS functions in fat bodies to regulate body weight and starvation resistance in Drosophila. HFD-induced obesity enhances CTPS transcription and lengthens cytoophidia in larval adipocytes. CTPS depletion in the fat body prevented HFD-induced obesity, including body weight gain, adipocyte expansion, and lipid accumulation, by inhibiting the PI3K-Akt-SREBP axis. A dominant-negative form of CTPS also inhibits adipocyte expansion and down-regulates lipogenic genes. As a result, our findings not only establish a functional link between CTPS and lipid homeostasis but also highlight a potential role of CTPS manipulation in the treatment of HFD-induced obesity.
2023-08-30 | GSE221707 | GEO
Project description:Obesity induced by high-fat diet (HFD) is a multi-factorial disease including genetic, physiological, behavioral, and environmental components. Drosophila has emerged as an effective metabolic disease model. Cytidine 5'-triphosphate synthase (CTPS) is an important enzyme for the de novo synthesis of CTP, governing the cellular level of CTP and the rate of phospholipid synthesis. CTPS is known to form filamentous structures called cytoophidia, which are found in bacteria, archaea, and eukaryotes. Our study demonstrates that CTPS is crucial in regulating body weight and starvation resistance in Drosophila by functioning in the fat body. HFD-induced obesity leads to increased transcription of CTPS and elongates cytoophidia in larval adipocytes. Depleting CTPS in the fat body prevented HFD-induced obesity, including body weight gain, adipocyte expansion, and lipid accumulation, by inhibiting the PI3K-Akt-SREBP axis. Furthermore, a dominant-negative form of CTPS also prevented adipocyte expansion and downregulated lipogenic genes. These findings not only establish a functional link between CTPS and lipid homeostasis but also highlight the potential role of CTPS manipulation in the treatment of HFD-induced obesity.
| S-EPMC10495109 | biostudies-literature
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 Metabolic disorders including obesity, impaired glucose tolerance, dyslipidemia, and insulin resistance constitute a global public health problem that increases the risk of cardiovascular and type 2 diabetes. In modern society, a major cause of metabolic disorder is excessive nutrient intake from food. Therefore, as the main site of nutrient absorption, the intestine plays an important role in diet-induced metabolic disorders. However, it is still largely unknown on how the intestine participates in such a process. Results Here we show that ‘ileal jejunization’ is responsible for high-fat diet-induced metabolic disorders in female mice. Upon HFD-feeding, the transcriptional profile of the ileum was shifted towards that of jejunum which is characterized by increased expression of jejunal feature genes. Accordantly, the lipids uptake was increased in the ileum. Importantly, the HFD-induced ileal jejunization and metabolic disorders can be profoundly attenuated by intestinal-specific reduction of RIPK1. Interestingly, the HFD-induced increase in the expression of the jejunal feature genes in the ileum, and the effect of RIPK1 reduction were not observed in male mice.
2025-03-05 | GSE282889 | GEO
Project description:Ramulus Mori (Sangzhi) alkaloids (SZ-A) alleviates nonalcoholic fatty liver disease in mice. This study compares transcriptome profiling (RNA-seq) in the liver of normal chow, high-fat diet (HFD) control and SZ-A-treated HFD mice to verify the regulatory mechanisms of SZ-A. These results demonstrated that SZ-A regulates lipid metabolism and metabolic stress-induced inflammation and fibrosis.
2022-03-23 | GSE199105 | GEO
Project description:Objectives: Studies have shown a correlation between obesity and mitochondrial calcium homeostasis, yet it is unclear whether and how Mcu regulates adipocyte lipid deposition. This study aims to provide new potential target for the treatment of obesity and related metabolic diseases, and to explore the function of Mcu in adipose tissue. Methods: We firstly investigated the role of mitoxantrone, an Mcu inhibitor, in the regulation of glucose and lipid metabolism in mouse adipocytes (3T3-L1 cells). Secondly, C57BL/6J mice were used as a research model to investigate the effects of Mcu inhibitors on fat accumulation and glucose metabolism in mice on a high-fat diet (HFD), and by using CRISPR/Cas9 technology, adipose tissue-specific Mcu knockdown mice (Mcu fl/+ AKO) and Mcu knockout of mice (Mcu fl/fl AKO) were obtained, to further investigate the direct effects of Mcu on fat deposition, glucose tolerance and insulin sensitivity in mice on a high-fat diet. Results: we found the Mcu inhibitor reduced adipocytes lipid accumulation and adipose tissues mass in mice fed an HFD. Both Mcu fl/+ AKO mice and Mcu fl/fl AKO mice were resistant to HFD-induced obesity, compared to control mice. Mice with Mcu fl/fl AKO showed improved glucose tolerance and insulin sensitivity as well as reduced hepatic lipid accumulation. Mechanistically, inhibition of Mcu promoted mitochondrial biogenesis and adipocyte browning, increase energy expenditure and alleviates diet-induced obesity. Conclusion: Our study demonstrates a link between adipocyte lipid accumulation and mCa2+ levels, suggesting that adipose-specific Mcu deficiency alleviates HFD-induced obesity and ameliorates metabolic disorders such as insulin resistance and hepatic steatosis. These effects may be achieved by increasing mitochondrial biosynthesis, promoting white fat browning and enhancing energy metabolism.
2023-11-12 | GSE247235 | GEO
Project description:In order to establish an obese mouse model, female mice were continuously fed with a high-fat diet (HFD) or a normal diet (control) for 16 weeks beginning at three weeks of age. In this paper, these mice are termed ‘HFD mice’ and ‘control mice’, respectively. Accordingly, we call their oocytes ‘HFD oocytes’ and ‘control oocytes’. Substantial evidence indicates that the effects of maternal obesity on embryo/offspring development can be attributed to factors within the oocyte (9). To identify such potential effectors, we performed a comparative proteomic analysis of ovulated MII oocytes from control and HFD mice.
2018-05-24 | PXD006641 | Pride
Project description:Fat body is an important tissue in the context of vitellogenesis, vector immunity, vector physiology and vector-parasite interaction. However, the proteome of this vital organ has not been investigated in any Anopheline species so far. In this study, we employed multiple fractionation method followed by high resolution mass spectrometry to characterize fat body proteome of female mosquitoes An. stephensi Indian strain. In all, we identified 4, 535 proteins in the fat body and a subset of these proteins were found to be restricted to fat body. Gene ontology analysis of these proteins suggested their role in metabolism, lipid transport, vitellogenesis, mosquito immunity and oxidation-reduction processes. By far, this is the largest proteomic resource of fat body in any mosquito species.
2019-01-07 | PXD006677 | Pride
Project description:In the present study, we explored whether skeletal muscle cystathionine γ-lyase (CTH) contributes to high-fat diet (HFD)-induced metabolic disorders using skeletal muscle Cth knockout (CthΔskm) mice. Metabolomics coupled with transcriptome showed that CthΔskm mice displayed impaired energy metabolism and some signaling pathways linked to insulin resistance (IR) in skeletal muscle although the mice had normal insulin sensitivity. HFD led to reduced CTH expression and impaired energy metabolism in skeletal muscle in Cth-floxed mice (Cthf/f) mice. CTH deficiency and HFD had some common pathways enriched in the aspects of amino acid metabolism, carbon metabolism, and fatty acid metabolism. CthΔskm+HFD mice exhibited increased body weight gain, fasting blood glucose, plasma insulin, and IR, and reduced glucose transporter 4 and CD36 expression in skeletal muscle compared to Cthf/f+HFD mice. Impaired mitochondria and irregular arrangement in myofilament occurred in CthΔskm+HFD mice. Omics analysis showed differential pathways enriched between CthΔskm mice and Cthf/f mice upon HFD. More severity in impaired energy metabolism, reduced AMPK signaling, and increased oxidative stress and ferroptosis occurred in CthΔskm+HFD mice compared to Cthf/f+HFD mice. Our data indicate that skeletal muscle CTH expression dysregulation contributes to metabolism disorders upon HFD.
2024-05-11 | GSE254704 | GEO
Project description:Liver-specific ceramide reduction alleviates steatosis and insulin resistance in alcohol-fed mice
| PRJNA578093 | ENA