scholarly journals Autophagy and Lipid Metabolism – A Cellular Platform where Molecular and Metabolic Pathways Converge to Explain Dengue Viral Infection

10.5772/61305 ◽  
2016 ◽  
Author(s):  
Elizabeth Orozco-García ◽  
Juan Carlos Gallego-Gómez
2021 ◽  
Vol 27 (1) ◽  
Author(s):  
Oliver C. Watkins ◽  
Preben Selvam ◽  
Reshma Appukuttan Pillai ◽  
Victoria K. B. Cracknell-Hazra ◽  
Hannah E. J. Yong ◽  
...  

Abstract Background Fetal docosahexaenoic acid (DHA) supply relies on preferential transplacental transfer, which is regulated by placental DHA lipid metabolism. Maternal hyperglycemia and obesity associate with higher birthweight and fetal DHA insufficiency but the role of placental DHA metabolism is unclear. Methods Explants from 17 term placenta were incubated with 13C-labeled DHA for 48 h, at 5 or 10 mmol/L glucose treatment, and the production of 17 individual newly synthesized 13C-DHA labeled lipids quantified by liquid chromatography mass spectrometry. Results Maternal BMI positively associated with 13C-DHA-labeled diacylglycerols, triacylglycerols, lysophospholipids, phosphatidylcholine and phosphatidylethanolamine plasmalogens, while maternal fasting glycemia positively associated with five 13C-DHA triacylglycerols. In turn, 13C-DHA-labeled phospholipids and triacylglycerols positively associated with birthweight centile. In-vitro glucose treatment increased most 13C-DHA-lipids, but decreased 13C-DHA phosphatidylethanolamine plasmalogens. However, with increasing maternal BMI, the magnitude of the glucose treatment induced increase in 13C-DHA phosphatidylcholine and 13C-DHA lysophospholipids was curtailed, with further decline in 13C-DHA phosphatidylethanolamine plasmalogens. Conversely, with increasing birthweight centile glucose treatment induced increases in 13C-DHA triacylglycerols were exaggerated, while glucose treatment induced decreases in 13C-DHA phosphatidylethanolamine plasmalogens were diminished. Conclusions Maternal BMI and glycemia increased the production of different placental DHA lipids implying impact on different metabolic pathways. Glucose-induced elevation in placental DHA metabolism is moderated with higher maternal BMI. In turn, findings of associations between many DHA lipids with birthweight suggest that BMI and glycemia promote fetal growth partly through changes in placental DHA metabolism.


2021 ◽  
Vol 12 ◽  
Author(s):  
Dongmei Chen ◽  
Jingquan He ◽  
Jinping Li ◽  
Qian Zou ◽  
Jiawei Si ◽  
...  

Psoriasis is a chronic inflammatory skin disease that affects millions of people worldwide. There is still no effective approach for the clinical treatment of psoriasis. This is largely due to the lack of understanding of the pathological mechanism. Here, we comprehensively characterized the skin microbiome and plasma metabolome alterations of psoriasis patients. We observed that some pathogenic bacteria, including Vibrio, were significantly increased in psoriasis patients. The metabolomics results showed alterations in some metabolic pathways, especially pathways for lipid metabolism. In addition, microbiome-specific metabolites, including bile acids and kynurenine, were significantly changed. Correlation analysis revealed the interplay between the skin microbiota and plasma metabolites, especially between Vibrio and several lipids. Our results provide new evidence for the interplay between the skin microbiome and plasma metabolites, which is dramatically disrupted in psoriasis patients. This study also revealed the mechanism underlying the pathogenesis of psoriasis.


2020 ◽  
Author(s):  
Hui DU ◽  
Yifei RAO ◽  
Ronghua LIU ◽  
Kesui DENG ◽  
Yongmei GUAN ◽  
...  

Abstract Background: Dyslipidemia is a common, chronic metabolic disease associated with cardiovascular complications. Due to the multiplicity of etiological factors, the pathogenesis of dyslipidemia is still unclear.Methods: In this study, we combined proteomics and metabolomics methods to analyze the plasma of patients with dyslipidemia and healthy subjects. ITRAQ markers, combined with LC-MS/MS proteomics technology and the UHPLC/ Orbitfast-X Tribrid system, were used to establish the metabolite profile in clinical dyslipidemia.Results: A total of 137 differentially expressed proteins were identified, mainly related to biological processes such as protein activation cascades, adaptive immune responses, complement activation, acute inflammatory responses and regulation of acute inflammatory responses. These proteins are involved in the regulation of important metabolic pathways, such as immunity and inflammation, coagulation and hemostasis, lipid metabolism, and oxidation and antioxidant defenses. Analysis of clinical metabolites showed there were 69 different metabolites in plasma, mainly related to glycerolipid, sphingolipid, porphyrin, alpha-linolenic acid, linoleic acid and arachidonic acid metabolism, suggesting that regulation of inflammation and lipid metabolism may be disturbed in patients with dyslipidemia. Among these, significant changes were observed in indole-3-propionic acid (IPA), which is considered a potential biomarker of dyslipidemia. Conclusions: Combined analysis of proteins and metabolites showed that arachidonic acid, linoleic acid and lipid metabolic pathways were closely related to dyslipidemia. IPA may be a potential biomarker.The information provided in this study may provide new insights into the pathogenesis of dyslipidemia and related diseases, as well as potential intervention targets.


2020 ◽  
Author(s):  
Xin LUO ◽  
Wancheng SUN ◽  
Yihao LUO

Abstract Background: Dietary sphingomyelin was showed to inhibit the uptake of lipids in mice fed with a high-fat diet, however, the effect of sphingomyelin on normal diet was on reported. The current study aims to examine the effects of sphingomyelin extracts from yak butter on hepatic steatosis and inflammation in C57/B6J mice fed with a normal diet. Methods: A UHPLC-QTOF-MS based lipidomics method was utilized to screen the liver metabolites and predict the dominant potential metabolic pathways after sphingomyelin feeding. Results: The results showed that sphingomyelin extracts reduced the accumulation of lipid droplets, suppressed the expression of pro-inflammatory factors IFN -γ, IL-6 and TNF - α, synchronously, promoted the expression of anti-inflammatory factors IL-10, IL-4 and IL-1Ra. In addition, sphingomyelin extracts exhibited the modulation on liver lipid metabolism when supplement sphingomyelin in normal diet for one month and five months. Specifically, 16, 68 different metabolites and 2, 6 metabolic pathways were identified by quantitative lipidomics, respectively. Six CERs including Cer(d18:1/18:0), Cer(d18:1/20:0), Cer(d17:1/22:0), Cer(d17:1/24:1), Cer(d17:1/24:0) and Cer(d17:0/26:1), six SMs including SM(d15:0/24:1), SM(d14:0/26:1), SM(d14:1/24:1), SM(d15:1/22:0), SM(d15:1/24:1) and SM(d19:1/26:1), and PS(18:1/22:6) were identified and can be used as potential biomarkers of steatosis and inflammation.Conclusions: This study highlighted the effects of yak butter sphingomyelin on hepatic steatosis, tissue inflammation and lipid metabolism of mice under a normal diet.


Author(s):  
Clyde F. Phelix ◽  
Richard G. LeBaron ◽  
Dawnlee J. Roberson ◽  
Rosa E. Villanueva ◽  
Greg Villareal ◽  
...  

The authors had validated a proprietary method, Transcriptome-To-Metabolome™ (TTM™) Biosimulation, for using the transcriptome to determine parameters for kinetic biosimulation of 16 core metabolic pathways. In vivo and in silico evidence confirmed that hippocampal cholesterol metabolism decreases with aging and increases with Alzheimer’s disease (AD). The molecular studies on aging primate and human hippocampus, including AD samples, provided internal validations on the biosimulations, while evidence from the literature, bibliome, provided external validations. This study extends the investigations with the TTM™ Biosimulations into the changes in these 16 metabolic pathways in aging male human hippocampus and for stages of AD. The authors report robust hippocampal hypometabolism in the fifth to tenth decade of life involving glucose and lipid metabolism in male humans. These findings are validated externally from the bibliome. Several changes in AD are demonstrated to be exaggerations or deviations of very late stage changes of normal aging among these pathways.


mBio ◽  
2017 ◽  
Vol 8 (5) ◽  
Author(s):  
Tanja V. Maier ◽  
Marianna Lucio ◽  
Lang Ho Lee ◽  
Nathan C. VerBerkmoes ◽  
Colin J. Brislawn ◽  
...  

ABSTRACT Diet can influence the composition of the human microbiome, and yet relatively few dietary ingredients have been systematically investigated with respect to their impact on the functional potential of the microbiome. Dietary resistant starch (RS) has been shown to have health benefits, but we lack a mechanistic understanding of the metabolic processes that occur in the gut during digestion of RS. Here, we collected samples during a dietary crossover study with diets containing large or small amounts of RS. We determined the impact of RS on the gut microbiome and metabolic pathways in the gut, using a combination of “omics” approaches, including 16S rRNA gene sequencing, metaproteomics, and metabolomics. This multiomics approach captured changes in the abundance of specific bacterial species, proteins, and metabolites after a diet high in resistant starch (HRS), providing key insights into the influence of dietary interventions on the gut microbiome. The combined data showed that a high-RS diet caused an increase in the ratio of Firmicutes to Bacteroidetes , including increases in relative abundances of some specific members of the Firmicutes and concurrent increases in enzymatic pathways and metabolites involved in lipid metabolism in the gut. IMPORTANCE This work was undertaken to obtain a mechanistic understanding of the complex interplay between diet and the microorganisms residing in the intestine. Although it is known that gut microbes play a key role in digestion of the food that we consume, the specific contributions of different microorganisms are not well understood. In addition, the metabolic pathways and resultant products of metabolism during digestion are highly complex. To address these knowledge gaps, we used a combination of molecular approaches to determine the identities of the microorganisms in the gut during digestion of dietary starch as well as the metabolic pathways that they carry out. Together, these data provide a more complete picture of the function of the gut microbiome in digestion, including links between an RS diet and lipid metabolism and novel linkages between specific gut microbes and their metabolites and proteins produced in the gut.


2001 ◽  
Vol 79 (6) ◽  
pp. 681-692 ◽  
Author(s):  
Christopher R McMaster

The movement of lipids from their sites of synthesis to ultimate intracellular destinations must be coordinated with lipid metabolic pathways to ensure overall lipid homeostasis is maintained. Thus, lipids would be predicted to play regulatory roles in the movement of vesicles within cells. Recent work has highlighted how specific lipid metabolic events can affect distinct vesicle trafficking steps and has resulted in our first glimpses of how alterations in lipid metabolism participate in the regulation of intracellular vesicles. Specifically, (i) alterations in sphingolipid metabolism affect the ability of SNAREs to fuse membranes, (ii) sterols are required for efficient endocytosis, (iii) glycerophospholipids and phosphorylated phosphatidylinositols regulate Golgi-mediated vesicle transport, (iv) lipid acylation is required for efficient vesicle transport mediated membrane fission, and (v) the addition of glycosylphosphatidylinositol lipid anchors to proteins orders them into distinct domains that result in their preferential sorting from other vesicle destined protein components in the endoplasmic reticulum. This review describes the experimental evidence that demonstrates a role for lipid metabolism in the regulation of specific vesicle transport events.Key words: vesicle transport, trafficking, lipid, sterol, metabolism.


2019 ◽  
Vol 20 (3) ◽  
pp. 644 ◽  
Author(s):  
Anika Dutta ◽  
Neelam Sharma-Walia

Lipids play a fundamental role in maintaining normal function in healthy cells. Their functions include signaling, storing energy, and acting as the central structural component of cell membranes. Alteration of lipid metabolism is a prominent feature of cancer, as cancer cells must modify their metabolism to fulfill the demands of their accelerated proliferation rate. This aberrant lipid metabolism can affect cellular processes such as cell growth, survival, and migration. Besides the gene mutations, environmental factors, and inheritance, several infectious pathogens are also linked with human cancers worldwide. Tumor viruses are top on the list of infectious pathogens to cause human cancers. These viruses insert their own DNA (or RNA) into that of the host cell and affect host cellular processes such as cell growth, survival, and migration. Several of these cancer-causing viruses are reported to be reprogramming host cell lipid metabolism. The reliance of cancer cells and viruses on lipid metabolism suggests enzymes that can be used as therapeutic targets to exploit the addiction of infected diseased cells on lipids and abrogate tumor growth. This review focuses on normal lipid metabolism, lipid metabolic pathways and their reprogramming in human cancers and viral infection linked cancers and the potential anticancer drugs that target specific lipid metabolic enzymes. Here, we discuss statins and fibrates as drugs to intervene in disordered lipid pathways in cancer cells. Further insight into the dysregulated pathways in lipid metabolism can help create more effective anticancer therapies.


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