Cardiovascular Research, Год журнала: 2024, Номер unknown
Опубликована: Сен. 13, 2024
Язык: Английский
Nature reviews. Cancer, Год журнала: 2024, Номер unknown
Опубликована: Окт. 1, 2024
Язык: Английский
Процитировано
9
BioEssays, Год журнала: 2025, Номер unknown
Опубликована: Янв. 19, 2025
ABSTRACT Adipose tissue (AT) inflammation, a hallmark of the metabolic syndrome, is triggered by overburdened adipocytes sending out immune cell recruitment signals during obesity development. An AT landscape persistent throughout weight loss and regain constitutes an immune‐obesogenic memory that hinders long‐term management. Lipid‐associated macrophages (LAMs) are emerging as major players in diseased, inflamed tissues may be key contributors to obesogenic AT. Our previous study found LAM abundance increases with via intermittent fasting (IF) obese mice, which driven adipocyte p53 signalling. However, specific causing accumulation under IF remain unknown. In this piece, we hypothesise on range adipocyte‐secreted can harbor immune‐attractive features upon fasting/refeeding cycles. We highlight possible mechanisms including death signalling, matrikines, other damage‐associated molecular patterns (DAMPs), well adipo(‐cyto)kines, lipid mediators, metabolites, extracellular vesicles, epigenetic rewiring. Finally, consider how advances gleaned from preclinical models might translatable management humans. Thus, provide vantage points driving monocyte recruitment, polarisation towards LAMs, retention, harness therapeutic potential modulating levels impacting disease.
Язык: Английский
Процитировано
1
Nature Reviews Cardiology, Год журнала: 2024, Номер unknown
Опубликована: Сен. 20, 2024
Язык: Английский
Процитировано
7
Frontiers in Immunology, Год журнала: 2025, Номер 15
Опубликована: Янв. 22, 2025
Immune cells adapt their metabolism in response to differentiation and activation status meet the energy demands for an appropriate immune response. Recent studies have elucidated that during cell metabolic reprogramming, lipid metabolism, including uptake, de novo synthesis fatty acid oxidation, undergoes significant alteration, resulting dynamic changes quantity quality of intracellular lipids. Given lipids serve as source structural components cellular membranes, they important implications physiological function. Myeloid cells, which are essential bridging innate adaptive immunity, sensitive these changes. Dysregulation myeloid can result dysfunction, chronic inflammation impaired resolution inflammation. Understanding mechanism by regulate function might provide novel therapeutic insights into inflammatory diseases, autoimmune diseases cancer. (143 words)
Язык: Английский
Процитировано
0
Cell Reports, Год журнала: 2025, Номер 44(2), С. 115310 - 115310
Опубликована: Фев. 1, 2025
Metabolic dysfunction-associated steatohepatitis (MASH) is characterized by injury to steatotic hepatocytes that triggers the release of endogenous danger-associated molecular patterns. Recent work demonstrated exposed lipid droplets (LDs) serve as a pathogenic signal promotes monocyte infiltration and its maturation into triggering receptor expressed in myeloid cells 2 (TREM2+) macrophages MASH liver. Here we explore role LD exposure modulating inflammatory signaling macrophages. We found efferocytosis global transcriptional response dampens pro-inflammatory treatment attenuated NLRP3 inflammasome activation via mechanisms independent lysosomal hydrolysis. While TREM2 was dispensable for macrophages, it required attenuation proinflammatory upon exposure. Additionally, MS4A7 downregulation contributes efferocytosis-mediated dampening response. These results underscore dual liver promoting TREM2+ macrophage induction, while restraining
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2025, Номер unknown
Опубликована: Март 1, 2025
Metabolic dysfunction-associated steatohepatitis (MASH) represents a progressive form of steatotic liver disease which increases the risk for fibrosis and advanced disease. The accumulation discrete species bioactive lipids has been postulated to activate signaling pathways that promote inflammation fibrosis. However, key pathogenic lipid is matter debate. We explored candidates using various dietary, molecular, genetic models. Mice fed choline-deficient L-amino acid-defined high-fat diet (CDAHFD) developed manifested early markers associated with increased cholesterol content in droplets within 5 days without any changes total content. Treating mice antisense oligonucleotides (ASOs) against Coenzyme A synthase (Cosay) or treatment bempedoic acid atorvastatin decreased droplet prevented CDAHFD-induced MASH fibrotic response. All these salutary effects were abrogated dietary supplementation. Analysis human samples demonstrated was humans higher PNPLA3 I148M (variants rs738409) than HSD17B13 variants (rs72613567). Together, data identify as critical mediator demonstrate COASY knockdown are novel therapeutic approaches reduce thereby prevent development linked role specific its pathogenesis remains debated. Using models, we found on choline-deficient, fibrosis, marked by five days. Targeting treating reduced MASH. supplementation negated effects. Human confirmed elevated especially carriers. These findings highlight reduction potential therapy.
Язык: Английский
Процитировано
0
bioRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown
Опубликована: Сен. 26, 2024
Abstract Macrophages are essential immune cells present in all tissues, and vital for maintaining tissue homeostasis, surveillance, responses. Considerable efforts have identified shared tissue-specific gene programs macrophages across organs during homeostasis. This information has dramatically enhanced our understanding of tissue-restricted macrophage programming function. However, few studies addressed the overlapping responses subsets following inflammatory One subset that been observed several studies, lipid-associated (LAMs), gained interest due to their unique role lipid metabolism potential as a therapeutic target. LAMs associated with regulating disease outcomes metabolically related disorders including atherosclerosis, obesity, nonalcoholic fatty liver (NAFLD). In this study, we utilized single-cell RNA sequencing (scRNAseq) data profile multiple tissues sterile conditions mice humans. Integration from various models revealed share set conserved transcriptional profiles, Trem2 Lpl , but also key sets LAM programs. Importantly, markers were highly human populations emerge chronic settings. Overall, analysis provides detailed landscape offers insights into roles metabolic diseases. These may help instruct appropriate targets broad or interventions modulate disease.
Язык: Английский
Процитировано
2
Frontiers in Immunology, Год журнала: 2024, Номер 15
Опубликована: Ноя. 20, 2024
Macrophages, the predominant immune cells in liver, are essential for maintaining hepatic homeostasis and responding to liver injury caused by external stressors. The macrophage population is highly heterogeneous plastic, mainly comprised of resident kuffer (KCs), monocyte-derived macrophages (MoMφs), lipid-associated (LAMs), capsular (LCMs). KCs, a macrophages, localized can self-renew through situ proliferation. However, MoMφs recruited from periphery circulation. LAMs self-renewing subgroup near bile duct. While LCMs located capsule derived peripheral monocytes. also involved damage induced various factors. Hepatic exhibit distinct phenotypes functions depending on specific microenvironment liver. KCs critical initiating inflammatory responses after sensing tissue damage, while infiltrated implicated both progression resolution chronic inflammation fibrosis. regulatory function fibrosis has attracted significant interest current research. Numerous literatures have documented that dual impact be categorized into two subtypes based their Ly-6C expression level: with high (referred as hi macrophages) reparative low lo macrophages). conducive occurrence fibrosis, associated degradation extracellular matrix (ECM) regression Given this, play pivotal role occurrence, progression, Based these studies, treatment therapies targeting being studied gradually. This review aims summarize researches composition origin heterogeneity anti-fibrosis therapeutic strategies
Язык: Английский
Процитировано
2
Nature, Год журнала: 2024, Номер 633(8031), С. 777 - 778
Опубликована: Сен. 11, 2024
Язык: Английский
Процитировано
1
Cancer Immunology Immunotherapy, Год журнала: 2024, Номер 73(12)
Опубликована: Окт. 3, 2024
Язык: Английский
Процитировано
1