Metabolic Fingerprinting Links Oncogenic PIK3CA with Enhanced Arachidonic Acid-Derived Eicosanoids

Cell, Journal Year: 2020, Volume and Issue: 181(7), P. 1596 - 1611.e27

Published: June 1, 2020

Oncogenic transformation is associated with profound changes in cellular metabolism, but whether tracking these can improve disease stratification or influence therapy decision-making largely unknown. Using the iKnife to sample aerosol of cauterized specimens, we demonstrate a new mode real-time diagnosis, coupling metabolic phenotype mutant PIK3CA genotype. results an increase arachidonic acid and concomitant overproduction eicosanoids, acting promote cell proliferation beyond cell-autonomous manner. Mechanistically, drives multimodal signaling network involving mTORC2-PKCζ-mediated activation calcium-dependent phospholipase A2 (cPLA2). Notably, inhibiting cPLA2 synergizes fatty acid-free diet restore immunogenicity selectively reduce PIK3CA-induced tumorigenicity. Besides highlighting potential for phenotyping stratified medicine, this study reveals important role activated PI3K regulating uncovering targetable vulnerability that depends on dietary fat restriction. VIDEO ABSTRACT.

Language: Английский

---

ALDH4A1 is an atherosclerosis auto-antigen targeted by protective antibodies

Nature, Journal Year: 2020, Volume and Issue: 589(7841), P. 287 - 292

Published: Dec. 2, 2020

Language: Английский

---

Arachidonic Acid as an Early Indicator of Inflammation during Non-Alcoholic Fatty Liver Disease Development

Biomolecules, Journal Year: 2020, Volume and Issue: 10(8), P. 1133 - 1133

Published: July 31, 2020

Non-alcoholic fatty liver disease (NAFLD) is a chronic characterized by excessive lipid deposition. Lipid metabolism disturbances are possibly associated with hepatocyte inflammation development and oxidative balance impairment. The aim of our experiment was to examine the first moment when changes in plasma arachidonic acid (AA) levels as pro-inflammatory precursor may occur during high-fat diet (HFD)-induced NAFLD development. Wistar rats were fed rich fat for five weeks, after each week, redox parameters evaluated liver. AA contents fractions assessed gas-liquid chromatography (GLC). Protein expression relevant inflammatory lipogenesis pathways determined immunoblotting. system indicators assay kits. Our results revealed that promoted an increase levels, especially phospholipid (PL) fraction. Importantly, rapid via increased enzyme expression, elevated peroxidation product content impairment caused HFD early week experiment. Based on these results, we postulate be indicator irreversible progression.

Language: Английский

---

Intestinal microbial metabolites in human metabolism and type 2 diabetes

Diabetologia, Journal Year: 2020, Volume and Issue: 63(12), P. 2533 - 2547

Published: Sept. 3, 2020

Abstract Humans with the metabolic syndrome and type 2 diabetes have an altered gut microbiome. Emerging evidence indicates that it is not only microorganisms their structural components, but also metabolites influences host contributes to development of diabetes. Here, we discuss some mechanisms underlying how microbial are recognised by or further processed endogenously in context We possibility gut-derived fuel

Language: Английский

---

Yellow Wine Polyphenolic Compound Protects Against Doxorubicin-Induced Cardiotoxicity by Modulating the Composition and Metabolic Function of the Gut Microbiota

Circulation Heart Failure, Journal Year: 2021, Volume and Issue: 14(10)

Published: Sept. 30, 2021

Dietary polyphenols help to prevent cardiovascular diseases, and interactions between gut microbiota are known exist. In this study, we speculated that microbiota-mediated metabolite regulation might contribute the anticardiotoxic effects of yellow wine polyphenolic compound (YWPC) in doxorubicin (DOX)-treated rats.

Language: Английский

---

Eicosanoids in inflammation in the blood and the vessel

Frontiers in Pharmacology, Journal Year: 2022, Volume and Issue: 13

Published: Sept. 27, 2022

Polyunsaturated fatty acids (PUFAs) are structural components of membrane phospholipids in cells. PUFAs regulate cellular function through the formation derived lipid mediators termed eicosanoids. The oxygenation 20-carbon via oxygenases cyclooxygenases, lipoxygenases, or cytochrome P450, generates a class classical eicosanoids including prostaglandins, thromboxanes and leukotrienes, also more recently identified hydroxy-, hydroperoxy-, epoxy- oxo-eicosanoids, specialized pro-resolving (lipid) mediators. These play critical role regulation inflammation blood vessel. While arachidonic acid-derived extensively studied due to their pro-inflammatory effects therefore involvement pathogenesis inflammatory diseases such as atherosclerosis, diabetes mellitus, hypertension, coronavirus disease 2019; recent years, several have been reported attenuate exacerbated responses participate resolution inflammation. This review focused on elucidating biosynthesis mechanistic signaling inflammation, well anti-inflammatory these vascular wall.

Language: Английский

---

Linoleic acid and the regulation of glucose homeostasis: A review of the evidence

Prostaglandins Leukotrienes and Essential Fatty Acids, Journal Year: 2021, Volume and Issue: 175, P. 102366 - 102366

Published: Oct. 29, 2021

Language: Английский

---

Lipid oxidation in pathophysiology of atherosclerosis: Current understanding and therapeutic strategies

International Journal of Cardiology Cardiovascular Risk and Prevention, Journal Year: 2022, Volume and Issue: 14, P. 200143 - 200143

Published: Aug. 4, 2022

A marked increase in the global prevalence of ischemic heart disease demands focused research for novel and more effective therapeutic strategies. At present, atherosclerotic cardiovascular (ACVD) is leading cause incidence attacks a major contributor to many peripheral cardiac diseases. Decades have unearthed complex multidimensional pathophysiology ACVD encompassing oxidative stress, redox imbalance, lipid peroxidation, pro-inflammatory signaling, hyperglycemic stress diabetes mellitus, chronic low-grade inflammation aging, immune dysregulation, vascular dysfunction, loss hemostasis, thrombosis, fluid shear stress. However, scientific basis interventions using conventional understandings mechanisms has been subject renewed scrutiny with findings recent years. This critical review attempts revise pathophysiological atherosclerosis body literature, focus on metabolism associated cellular biochemical processes. The comprehensive study encompasses different molecular perspectives development progression coronary atherosclerosis. also summarizes currently prescribed small molecule therapeutics ACVD, overviews prospective management measures under including peptides microRNA therapeutics. provides updated insights into current knowledge atherosclerosis, highlights need prevention, intervention approaches overcome this epidemic.

Language: Английский

---

An Effective Glucagon-Like Peptide-1 Receptor Agonists, Semaglutide, Improves Sarcopenic Obesity in Obese Mice by Modulating Skeletal Muscle Metabolism

Drug Design Development and Therapy, Journal Year: 2022, Volume and Issue: Volume 16, P. 3723 - 3735

Published: Oct. 1, 2022

Purpose: This study aimed to investigate the effect of Semaglutide on skeletal muscle and its metabolomics. Methods: A total 18 male C57BL/6 mice were randomly divided into normal control (NC) group, high-fat diet (HFD) group HFD+Semaglutide given standard diet, HFD plus Semaglutide, respectively. The body weight, gastrocnemius serum lipid, blood glucose inflammatory index levels in each observed compared, morphological structural changes also analyzed. Meanwhile, metabolite analyzed by untargeted Results: After treatment, food intake weight evidently decreased, while relative ratio conversely increased. TG, CHO, LDL, HDL, TNF-α, IL-6, IL-1β HOMA-IR all decrease remarkably after intervention. Histological analysis showed that significantly improved pathological gastrocnemius, manifested as increased type I/type II fiber ratio, area, density, sarcomere length, mitochondrial number area. Furthermore, metabolic intervention analyzed, 141 kinds differential metabolites screened out, mainly embodied lipids organic acids, enriched 9 pathways including a variety amino acids. Conclusion: can reduce accumulation intramuscular fat, promote protein synthesis, increase proportion muscle, improve function obese mice, possibly altering metabolism Keywords: sarcopenic obesity, sarcopenia, glucagon-like peptide-1 receptor agonists, metabonomics

Language: Английский

---

Modified Lipoproteins Induce Arterial Wall Inflammation During Atherogenesis

Frontiers in Cardiovascular Medicine, Journal Year: 2022, Volume and Issue: 9

Published: March 3, 2022

Circulating apolipoprotein B-containing lipoproteins, notably the low-density enter inner layer of arterial wall, intima, where a fraction them is retained and modified by proteases, lipases, oxidizing agents enzymes. The lipoproteins various modification products, such as fatty acids, ceramides, lysophospholipids, oxidized lipids induce inflammatory reactions in macrophages covering endothelial cells, initiating an increased leukocyte diapedesis. Lipolysis also induces formation cholesterol crystals with strong proinflammatory properties. Modified aggregated crystals, isolated from human atherosclerotic lesions, all can activate thereby secretion cytokines, chemokines, extent lipoprotein retention, modification, aggregation have been shown to depend largely on differences composition circulating particles. These properties be pharmacological means, provide opportunities for clinical interventions regarding prevention treatment vascular diseases.

Language: Английский

---