The role of efferocytosis‐fueled macrophage metabolism in the resolution of inflammation

Immunological Reviews, Год журнала: 2023, Номер 319(1), С. 65 - 80

Опубликована: Май 9, 2023

Summary The phagocytosis of dying cells by macrophages, termed efferocytosis, is a tightly regulated process that involves the sensing, binding, engulfment, and digestion apoptotic cells. Efferocytosis not only prevents tissue necrosis inflammation caused secondary cells, but it also promotes pro‐resolving signaling in which essential for resolution repair following injury or inflammation. An important factor contributes to this reprogramming cargo released from after their engulfment phagolysosomal macrophages. cell contains amino acids, nucleotides, fatty cholesterol function as metabolites molecules bring about re‐programming. Here, we review efferocytosis‐induced changes macrophage metabolism mediate functions We discuss various strategies, challenges, future perspectives related drugging efferocytosis‐fueled strategy dampen promote chronic inflammatory diseases.

Язык: Английский

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Plasma Proteomic Kinetics in Response to Acute Exercise

Molecular & Cellular Proteomics, Год журнала: 2023, Номер 22(8), С. 100601 - 100601

Опубликована: Июнь 20, 2023

Regular exercise has many favorable effects on human health, which may be mediated in part by the release of circulating bioactive factors during each bout exercise. Limited data exist regarding kinetic responses plasma proteins and after acute Proteomic profiling 4163 was performed using a large-scale, affinity-based platform 75 middle-aged adults who were referred for treadmill stress testing. Plasma quantified at baseline, peak exercise, 1-h postexercise, those with significant changes both timepoints further examined their associations cardiometabolic traits change aerobic training Health, Risk Factors, Exercise Training Genetics Family Study, 20-week intervention study. A total 765 changed (false discovery rate < 0.05) compared to 128 postexercise. The 56 that included midkine, brain-derived neurotrophic factor, metalloproteinase inhibitor 4, coiled-coil domain-containing protein 126 enriched secreted proteins. majority had concordant direction timepoints. Across all assayed, gene set enrichment analysis showed increased abundance coagulation-related Forty-five associated least one measure adiposity, lipids, glucose homeostasis, or cardiorespiratory fitness 20 training. We identified hundreds novel most resolved 1 h into recovery. Proteins sustained recovery particular interest as biomarkers pathways investigation diseases. These will contribute biochemical roadmap publicly available entire scientific community.

Язык: Английский

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Should the standard model of cellular energy metabolism be reconsidered? Possible coupling between the pentose phosphate pathway, glycolysis and extra-mitochondrial oxidative phosphorylation

Biochimie, Год журнала: 2024, Номер 221, С. 99 - 109

Опубликована: Фев. 1, 2024

The process of cellular respiration occurs for energy production through catabolic reactions, generally with glucose as the first step. In present work, we introduce a novel concept understanding this process, based on our conclusion that metabolism is coupled to pentose phosphate pathway (PPP) and extra-mitochondrial oxidative phosphorylation in closed-loop process. According current standard model glycolysis, converted 6-phosphate (glucose 6-P) then fructose 6-phosphate, glyceraldehyde 3-phosphate pyruvate, which enters Krebs cycle mitochondria. However, it more likely pyruvate will be lactate. PPP, 6-P branched off from glycolysis used produce NADPH ribulose 5-phosphate (ribulose 5-P). Ribulose 5-P can 3-P. view, circular take place produced by PPP retrogradely 6-P. This repeated several times until complete degradation role mitochondria degrade lipids beta-oxidation acetyl-CoA; function producing ATP appears only secondary. proposed new bioenergetics allows resolution some previously unresolved controversies related provides deeper metabolic processes cell, including insights into Warburg effect.

Язык: Английский

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Lactate-induced autophagy activation: unraveling the therapeutic impact of high-intensity interval training on insulin resistance in type 2 diabetic rats

Scientific Reports, Год журнала: 2024, Номер 14(1)

Опубликована: Янв. 11, 2024

Impaired autophagy is a hallmark of diabetes. The current study proposed to investigate if high intensity interval training (HIIT) induced lactate accumulation could stimulate in type 2 diabetic male rats. 28 Wistar rats were randomly assigned into four groups: Healthy Control (CO), Diabetes (T2D), Exercise (EX), and + (T2D EX). was by feeding high-fat diet administrating single dose streptozotocin (35 mg/kg). After becoming diabetic, the animals exercise groups (EX T2D EX) performed an eight-week HIIT (4-10 interval, 80-100% Vmax, 5 days per week). Serum levels lactate, glucose insulin as well pyruvate, transporter monocarboxylate 1 (MCT1), phosphorylated mitogen-activated protein kinases (p-MAP 2), extracellular signal-regulated (p-ERK mammalian target rapamycin (p-mTOR), ribosomal S6 kinase beta-1 (p-70S6k), p90 (p-90RSK), related 7 (ATG7), Beclin-1, microtubule-associated 1A/1B, 2A/2B -light chain 3 (LC3-I), (LC3- II), (LC3I/LC3II) soleus muscle measured. Homeostatic Model Assessment for Insulin Resistance (HOMA-IR) serum lower EX compared group (P < 0.0001). While not different between Ex, Pyruvate 0.01), MCT1, p-ERK1/2, p-mTOR, p70S6k, P-90RSK, ATG7, LC3-II, LC3-II/LC3I ratios higher We concluded that eight weeks high-intensity activated ERK/P90SRK while inhibiting mTOR/P70S6K signaling pathway dependent manner. It means increased which resulted improve resistance (IR) reduce blood glucose.

Язык: Английский

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Enteric and systemic postprandial lactate shuttle phases and dietary carbohydrate carbon flow in humans

Nature Metabolism, Год журнала: 2024, Номер 6(4), С. 670 - 677

Опубликована: Фев. 22, 2024

Abstract Dietary glucose in excess is stored the liver form of glycogen. As opposed to direct conversion into glycogen, hypothesis postprandial lactate shuttle (PLS) proposes that dietary uptake metabolized gut, thereby being transferred for glycogen storage. In present study, we provide evidence a PLS young healthy men and women. Overnight fasted participants underwent an oral tolerance test, arterialized concentration rate appearance were determined. The blood rose before glucose, thus providing enteric PLS. Secondary increments its coincided with those which indicates presence larger, secondary, systemic phase driven by hepatic release. study challenges notion production result hypoxia skeletal muscles, because our work glycolysis proceeds fully aerobic tissues carbohydrate processed via shuttling. Our that, humans, major vehicle carbon distribution metabolism.

Язык: Английский

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Training Elite Athletes: 50 Years of Thinking About Practice and Research for Endurance Sports

Scandinavian Journal of Medicine and Science in Sports, Год журнала: 2025, Номер 35(1)

Опубликована: Янв. 1, 2025

ABSTRACT This essay summarizes and integrates my experiences observations—starting in the middle 1970s—as an athlete, scientist interested human performance, biomedical researcher, “expert,” who sometimes advises athletes, coaches, sports policy‐makers. In this context, focus has been primarily on endurance five concepts underpin what I have learned over last 50 years. (1) The “competitive significance principle” whereby policy‐makers are frequently performance improvements of 1% or less. is especially true at elite level. (2) Science explains coaches athletes already discovered field. (3) Many science‐based reduced energy cost moving a given speed. (4) Varied eclectic training programs used by with similar outcomes. (5) A few things that actionable matter. Coaches, administrators should their efforts actionable.

Язык: Английский

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A High-Fat Diet Induces Epigenetic 1-Carbon Metabolism, Homocystinuria, and Renal-Dependent HFpEF

Nutrients, Год журнала: 2025, Номер 17(2), С. 216 - 216

Опубликована: Янв. 8, 2025

Chronic gut dysbiosis due to a high-fat diet (HFD) instigates cardiac remodeling and heart failure with preserved ejection fraction (HFpEF), in particular, kidney/volume-dependent HFpEF. Studies report that although mitochondrial ATP citrate lyase (ACLY) supports function, it decreases more human HFpEF than HFrEF. Interestingly, ACLY synthesizes lipids creates hyperlipidemia. Epigenetically, acetylates histone. The mechanism(s) are largely unknown. One hypothesis is an HFD induces epigenetic folate 1-carbon metabolism (FOCM) homocystinuria. This abrogates dipping sleep-time blood pressure causes hypertension morning attacks. We observed probiotics/lactobacillus utilize fat/lipids post-biotically, increasing bioenergetics attenuating suggest novel paradigm-shift sulfur trans-sulfuration pathways selectively target HFD-induced Previous studies from our laboratory, using single-cell analysis, revealed increase the transporter (SLC25A) of s-adenosine-methionine (SAM) during elevated levels homocysteine (Hcy, i.e., homocystinuria, HHcy), consequence impaired recycling Hcy back methionine FOCM methylation H3K4, K9, H4K20, gene writer (DNMT) decrease eraser (TET/FTO). transported mitochondria by SLC7A for clearance via metabolomic 3-mercaptopyruvate transferase (3MST). conclude disrupts rhythmic memory increases DNMT1 leading bioenergetics. treatment lactobacillus metabolites post-biotically bi-directionally produces folic acid lactone-ketone body mitigates

Язык: Английский

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Lactate homeostasis is maintained through regulation of glycolysis and lipolysis

Cell Metabolism, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Examining the Interaction between Exercise, Gut Microbiota, and Neurodegeneration: Future Research Directions

Biomedicines, Год журнала: 2023, Номер 11(8), С. 2267 - 2267

Опубликована: Авг. 14, 2023

Physical activity has been demonstrated to have a significant impact on gut microbial diversity and function. Emerging research revealed certain aspects of the complex interactions between gut, exercise, microbiota, neurodegenerative diseases, suggesting that changes in metabolic function may an onset progression neurological conditions. This study aimed review current literature from several databases until 1 June 2023 (PubMed/MEDLINE, Web Science, Google Scholar) interplay physical neurodegeneration. We summarized roles exercise microbiota neurodegeneration identified ways which these are all connected. The gut–brain axis is multifaceted network gained considerable attention recent years. Research indicates plays vital shifts during physiological or pathophysiological conditions diseases; therefore, they closely related maintaining overall health well-being. Similarly, shown positive effects brain cognitive function, reduce/delay severe disorders. Exercise associated with various neurochemical changes, including alterations cortisol levels, increased production endorphins, endocannabinoids like anandamide, as well higher levels serotonin dopamine. These linked mood improvements, enhanced sleep quality, better motor control, enhancements resulting exercise-induced effects. However, further clinical necessary evaluate bacteria taxa along age- sex-based differences.

Язык: Английский

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Glycolysis Reprogramming in Idiopathic Pulmonary Fibrosis: Unveiling the Mystery of Lactate in the Lung

International Journal of Molecular Sciences, Год журнала: 2023, Номер 25(1), С. 315 - 315

Опубликована: Дек. 25, 2023

Idiopathic pulmonary fibrosis (IPF) is a chronic and progressive lung disease characterized by excessive deposition of fibrotic connective tissue in the lungs. Emerging evidence suggests that metabolic alterations, particularly glycolysis reprogramming, play crucial role pathogenesis IPF. Lactate, once considered waste product, now recognized as signaling molecule involved various cellular processes. In context IPF, lactate has been shown to promote fibroblast activation, myofibroblast differentiation, extracellular matrix remodeling. Furthermore, can modulate immune responses contribute pro-inflammatory microenvironment observed addition, implicated crosstalk between different cell types IPF; it influence cell-cell communication, cytokine production, activation profibrotic pathways. This review aims summarize current research progress on glycolytic reprogramming IPF its potential implications clarify provide reference direction for future research. conclusion, elucidating intricate interplay metabolism processes may lead development innovative therapeutic strategies

Язык: Английский

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