Hyperuricemia induces lipid disturbances by upregulating the CXCL-13 pathway

2021 ◽  
Author(s):  
Jin Meng ◽  
Qiulan Lv ◽  
Aihua Sui ◽  
Daxing Xu ◽  
Tong Zou ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Droplets ◽  
Acid Synthesis ◽  
Mice Model ◽  
Ampk Signaling ◽  
Protein Protein Interaction ◽  
Lipid Metabolism Disorders ◽  
Protein Protein Interaction Networks

The molecular mechanism underlying hyperuricemia-induced lipid metabolism disorders is not clear. The purpose of the current study was to investigate the mechanism of lipid disturbances in a hyperuricemia mice model. RNAseq showed that differentially expressed genes (DEGs) in the fatty acid synthesis signaling pathway were mainly enriched, and CXCL-13 was significantly enriched in protein-protein interaction networks. Western blotting, Q-PCR, and immunofluorescence results further showed that hyperuricemia upregulated CXCL-13 and disturbed lipid metabolism in vivo and in vitro. Furthermore, CXCL-13 alone also promoted the accumulation of lipid droplets and upregulated the expression of FAS and SREBP1, blocking AMPK signaling and activating the PKC and P38 signaling pathways. Silencing CXCL-13 reversed uric-acid-induced lipid droplet accumulation, which further downregulated FAS and SREBP1 expression, inhibited the p38 and PKC signaling, and activated AMPK signaling. In conclusion, hyperuricemia induces lipid metabolism disorders via the CXCL-13 pathway, making CXCL-13 a key regulatory factor linking hyperuricemia and lipid metabolism disorders. These results may provide novel insights for the treatment of hyperuricemia.

scholarly journals Glucagon regulates ACC activity in adipocytes through the CAMKKβ/AMPK pathway

2012 ◽  
Vol 302 (12) ◽  
pp. E1560-E1568 ◽  
Author(s):  
I-Chen Peng ◽  
Zhen Chen ◽  
Wei Sun ◽  
Ying-Shiuan Li ◽  
Traci LaNai Marin ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Lipid Metabolism ◽  
Protein Kinase ◽  
Fatty Acid Synthesis ◽  
Acid Synthesis ◽  
Dependent Protein Kinase ◽  
Ampk Signaling ◽  
Dependent Protein

Glucagon is important for regulating lipid metabolism in part through its inhibition of fatty acid synthesis in adipocytes. Acetyl-CoA carboxylase 1 (ACC1) is the rate-limiting enzyme for fatty acid synthesis. Glucagon has been proposed to activate cAMP-dependent protein kinase A (PKA), which phosphorylates ACC1 to attenuate the lipogenic activity of ACC1. Because AMP-activated protein kinase (AMPK) also inhibits fatty acid synthesis by phosphorylation of ACC1, we examined the involvement of AMPK and its upstream kinase in the glucagon-elicited signaling in adipocytes in vitro and in vivo. LC-MS-MS analysis suggested that ACC1 was phosphorylated only at Ser79, an AMPK-specific site, in glucagon-treated adipocytes. Pharmacological inhibitors and siRNA knockdown of AMPK or PKA in adipocytes demonstrate that glucagon regulates ACC1 and ACC2 activity through AMPK but not PKA. By using Ca2+/calmodulin-dependent protein kinase kinase-β knockout (CaMKKβ−/−) mice and cultured adipocytes, we further show that glucagon activates the CaMKKβ/AMPK/ACC cascade. Additionally, fasting increases the phosphorylation of AMPK and ACC in CaMKKβ+/+ but not CaMKKβ−/− mice. These results indicate that CaMKKβ/AMPK signaling is an important molecular component in regulating lipid metabolism in adipocytes responding to glucagon and could be a therapeutic target for the dysregulation of energy storage.

scholarly journals Liraglutide Attenuates Nonalcoholic Fatty Liver Disease through Adjusting Lipid Metabolism via SHP1/AMPK Signaling Pathway

2019 ◽  
Vol 2019 ◽  
pp. 1-11 ◽  
Author(s):  
Peng Yu ◽  
Xi Xu ◽  
Jing Zhang ◽  
Xuan Xia ◽  
Fen Xu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Liver Disease ◽  
Fatty Liver ◽  
Nonalcoholic Fatty Liver Disease ◽  
Hepg2 Cells ◽  
Fatty Liver Disease ◽  
Nonalcoholic Fatty Liver ◽  
Ampk Signaling

A glucagon-like peptide-1 (GLP-1) receptor agonist liraglutide (LR) had been experimentally and clinically shown to ameliorate nonalcoholic fatty liver disease (NAFLD). This study aimed to investigate the beneficial effect of LR on NAFLD in vivo and in vitro and its underlying molecular mechanism. The effects of LR were examined on the high-fat diet-induced in vivo model in mice and in vitro model of NAFLD in human HepG2 cells. Liver tissues and HepG2 cells were procured for measuring lipid metabolism, histological examination, and western blot analysis. LR administration significantly lowered the serum lipid profile and lipid disposition in vitro and in vivo because of the altered expression of enzymes on hepatic gluconeogenesis and lipid metabolism. Moreover, LR significantly decreased Src homology region 2 domain-containing phosphatase-1 (SHP1) and then increased the expression of phosphorylated-AMP-activated protein kinase (p-AMPK). However, the overexpression of SHP1 mediated by lentivirus vector reversed LR-induced improvement in lipid deposition. Moreover, SHP1 silencing could further increase the expression of p-AMPK to ameliorate lipid metabolism and relative lipogenic gene induced by LR. In addition, abrogation of AMPK by Compound C eliminated the protective effects of LR on lipid metabolism without changing the expression of SHP1. LR markedly prevented NAFLD through adjusting lipid metabolism via SHP1/AMPK signaling pathway.

scholarly journals Breed-specific factors influence embryonic lipid composition: comparison between Jersey and Holstein

2016 ◽  
Vol 28 (8) ◽  
pp. 1185 ◽  
Author(s):  
Luis Baldoceda ◽  
Isabelle Gilbert ◽  
Dominic Gagné ◽  
Christian Vigneault ◽  
Patrick Blondin ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Lipid Composition ◽  
Lipid Droplets ◽  
Cell Damage ◽  
Poor Performance ◽  
Culture Conditions ◽  
Mitochondrial Activity ◽  
The Impact

Some embryos exhibit better survival potential to cryopreservation than others. The cause of such a phenotype is still unclear and may be due to cell damage during cryopreservation, resulting from overaccumulation and composition of lipids. In cattle embryos, in vitro culture conditions have been shown to impact the number of lipid droplets within blastomeres. Thus far, the impact of breed on embryonic lipid content has not been studied. In the present study were compared the colour, lipid droplet abundance, lipid composition, mitochondrial activity and gene expression of in vivo-collected Jersey breed embryos, which are known to display poor performance post-freezing, with those of in vivo Holstein embryos, which have good cryotolerance. Even when housed and fed under the same conditions, Jersey embryos were found to be darker and contain more lipid droplets than Holstein embryos, and this was correlated with lower mitochondrial activity. Differential expression of genes associated with lipid metabolism and differences in lipid composition were found. These results show genetic background can impact embryonic lipid metabolism and storage.

Galectin-3 Mediates Cardiac Remodeling Caused by Impaired Glucose and Lipid Metabolism Through Inhibiting Two Pathways of Activating Akt

2020 ◽  
Author(s):  
Zhen Sun ◽  
Lili Zhang ◽  
Lihua Li ◽  
Chen Shao ◽  
Jia Liu ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Cardiac Remodeling ◽  
Density Lipoprotein ◽  
Myocardial Damage ◽  
Diabetic Patients ◽  
Glucose And Lipid Metabolism ◽  
Lipid Metabolism Disorders ◽  
Galectin 3

Pathological cardiac remodeling is a leading cause of mortality in diabetic patients. Given the glucose and lipid metabolism disorders (GLD) in diabetic patients, it is urgent to conduct a comprehensive study of the myocardial damage under GLD and find key mechanisms. Apolipoprotein E knockout (ApoE-/-) mice, low-density lipoprotein receptor heterozygote (Ldlr+/-) syrian golden hamsters or H9C2 cells were used to construct GLD models -. And GLD significantly promoted cardiomyocyte fibrosis, apoptosis and hypertrophy in vivo and in vitro, while inhibition of galectin-3 (Gal-3) could significantly reverse this process. Then, the signal transmission pathways were determined. It was found that GLD considerably inhibited the phosphorylation of Akt at Thr308 / Ser473, whereas the silencing of Gal-3 could reverse the inhibition of Akt activity through PI3K-AktThr308 and AMPK-mTOR2-AktSer473 pathways. Finally, the PI3K, mTOR, AMPK inhibitor and Akt activator were used to investigate the role of pathways in regulating cardiac remodeling. Phospho-AktThr308 could mediate myocardial fibrosis, while myocardial apoptosis and hypertrophy were regulated by both phospho-AktThr308 and phospho-AktSer473. In conclusion, Gal-3 was an important regulatory factor in GLD-induced cardiac remodeling, and Gal-3 could suppress the phosphorylation of Akt at different sites in mediating cardiomyocyte fibrosis, apoptosis and hypertrophy.

scholarly journals Effect ofCentella asiaticaon Oxidative Stress and Lipid Metabolism in Hyperlipidemic Animal Models

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Yun Zhao ◽  
Ping Shu ◽  
Youzhi Zhang ◽  
Limin Lin ◽  
Haihong Zhou ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Lipid Metabolism ◽  
Metabolic Diseases ◽  
Centella Asiatica ◽  
Ethanol Extract ◽  
Hypolipidemic Effect ◽  
Mice Model ◽  
Hamster Model

Hyperlipidemia and many other metabolic diseases are related to oxidative stress.Centella asiaticais a traditional Chinese medicine whose antioxidant effect in vitro has been reported. We are interested in whether it possesses this effect in vivo and hence modulates lipid metabolism. Therefore, experiments were carried out on mice and golden hamsters regarding its antioxidant and hypolipidemic effect. We observed that a fraction (CAF3) of the ethanol extract (CAE) ofCentella asiaticahad a cholesterol decrease of 79% and a triglyceride decrease of 95% in acute mice model, so CAF3 was further investigated in high-fat-fed hamster model. It was shown that CAF3 increased SOD and GSH-Px activities and decreased MDA level, and it also improved TC, TG, LDL-C, HDL-C, AST, and ALT levels. L-CAT and SR-BI gene expression in hamsters were increased. Taken together, our data suggest that the CAF3 fraction ofCentella asiaticahas antioxidant and hypolipidemic properties.

scholarly journals In vivo interactome profiling by enzyme‐catalyzed proximity labeling

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Yangfan Xu ◽  
Xianqun Fan ◽  
Yang Hu
Keyword(s):  
State Of The Art ◽  
Catalytic Efficiency ◽  
Biological Processes ◽  
Protein Protein Interaction ◽  
Current State ◽  
Protein Interactome ◽  
Potential Applications ◽  
Protein Protein Interaction Networks ◽  
Temporal And Spatial

AbstractEnzyme-catalyzed proximity labeling (PL) combined with mass spectrometry (MS) has emerged as a revolutionary approach to reveal the protein-protein interaction networks, dissect complex biological processes, and characterize the subcellular proteome in a more physiological setting than before. The enzymatic tags are being upgraded to improve temporal and spatial resolution and obtain faster catalytic dynamics and higher catalytic efficiency. In vivo application of PL integrated with other state of the art techniques has recently been adapted in live animals and plants, allowing questions to be addressed that were previously inaccessible. It is timely to summarize the current state of PL-dependent interactome studies and their potential applications. We will focus on in vivo uses of newer versions of PL and highlight critical considerations for successful in vivo PL experiments that will provide novel insights into the protein interactome in the context of human diseases.

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