Lipid-associated macrophages between aggravation and alleviation of metabolic diseases

Trends in Endocrinology and Metabolism, Год журнала: 2024, Номер 35(11), С. 981 - 995

Опубликована: Май 4, 2024

Lipid-associated macrophages (LAMs) are phagocytic cells with lipid-handling capacity identified in various metabolic derangements. During disease development, they locate to atherosclerotic plaques, adipose tissue (AT) of individuals obesity, liver lesions steatosis and steatohepatitis, the intestinal lamina propria. LAMs can also emerge metabolically demanding microenvironment certain tumors. In this review, we discuss major questions regarding LAM recruitment, differentiation, self-renewal, and, ultimately, their acute chronic functional impact on development diseases. Further studies need clarify whether under which circumstances drive progression or resolution how phenotype be modulated ameliorate disorders.

Язык: Английский

---

The role of fibrosis in endometriosis: a systematic review

Human Reproduction Update, Год журнала: 2024, Номер 30(6), С. 706 - 750

Опубликована: Июль 8, 2024

Abstract BACKGROUND Fibrosis is an important pathological feature of endometriotic lesions all subtypes. present in and around lesions, a central role its development played by myofibroblasts, which are cells derived mainly after epithelial-to-mesenchymal transition (EMT) fibroblast-to-myofibroblast transdifferentiation (FMT). Transforming growth factor-β (TGF-β) has key this myofibroblastic differentiation. Myofibroblasts deposit extracellular matrix (ECM) have contracting abilities, leading to stiff micro-environment. These aspects hypothesized be involved the origin endometriosis-associated pain. Additionally, similarities between endometriosis-related fibrosis other fibrotic diseases, such as systemic sclerosis or lung fibrosis, indicate that targeting could potential therapeutic strategy for non-hormonal therapy endometriosis. OBJECTIVE AND RATIONALE This review aims summarize current knowledge highlight gaps about A comprehensive literature overview endometriosis can improve efficiency fibrosis-oriented research SEARCH METHODS systematic search was performed three biomedical databases using terms ‘endometriosis’, ‘fibrosis’, ‘myofibroblasts’, ‘collagen’, ‘α-smooth muscle actin’. Original studies were included if they reported Both preclinical vitro animal studies, well concerning human subjects included. OUTCOMES Our yielded 3441 results, 142 review. Most scored high moderate risk bias according assessment tools. The divided categories: observational experimental with human-derived material, studies. showed details histologic appearance co-occurrence nerves immune lesions. identified several pro-fibrotic pathways relation assessed effect strategies halt regress example platelets mast cells. WIDER IMPLICATIONS shows main cellular driver, myofibroblast, Platelets TGF-β pivotal signaling. presence neuropeptides closely associated likely cause process EMT FMT shares characteristics so exploring known processes diseases like sclerosis, idiopathic pulmonary liver cirrhosis relevant promising direction explore new treatment strategies. close relationship appears rather unique not observed diseases. REGISTRATION NUMBER N/A.

Язык: Английский

---

Emerging advanced approaches for diagnosis and inhibition of liver fibrogenesis

The Egyptian Journal of Internal Medicine, Год журнала: 2024, Номер 36(1)

Опубликована: Фев. 12, 2024

Abstract Background Liver fibrosis results from chronic liver injury and is characterized by excessive deposition of extracellular matrix proteins including collagen. It can progress to cirrhosis failure. Main body the abstract Multiple cellular signaling pathways drive hepatic stellate cell activation fibrogenesis. Advances in biomarkers, imaging modalities, omics platforms enable noninvasive diagnosis staging fibrosis. Emerging antifibrotic approaches include medications like pirfenidone, obeticholic acid, monoclonal antibodies targeting pro-fibrotic mediators. Cell therapies using mesenchymal stem cells demonstrate potential through paracrine immunosuppression. Tissue-engineered grafts biomaterial carriers for localized drug delivery are promising technologies. Microfluidic liver-on-a-chip with patient-derived provide unprecedented models study human test candidates. Short conclusion Significant has elucidated mechanisms underlying fibrogenesis uncovered novel therapeutic targets. Ongoing challenges translating preclinical findings, improving efficacy, enabling personalized precision medicine approaches. Further research into combinatorial therapies, tissue engineering technologies will advance treatment all causes.

Язык: Английский

---

Protocol to generate human liver spheroids to study liver fibrosis induced by metabolic stress

STAR Protocols, Год журнала: 2024, Номер 5(2), С. 103111 - 103111

Опубликована: Июнь 1, 2024

Currently, there is no effective treatment for obesity and alcohol-associated liver diseases, partially due to the lack of translational human models. Here, we present a protocol generate 3D spheroids that contain all cell types mimic "livers in dish." We describe strategies induce metabolic hepatic steatosis, inflammation, fibrosis. outline potential applications, including using experimental research drug screening identify anti-fibrotic therapies.

Язык: Английский

---

From liver to hormones: The endocrine consequences of cirrhosis

World Journal of Gastroenterology, Год журнала: 2024, Номер 30(9), С. 1073 - 1095

Опубликована: Март 5, 2024

Hepatocrinology explores the intricate relationship between liver function and endocrine system. Chronic diseases such as cirrhosis can cause disorders due to toxin accumulation protein synthesis disruption. Despite its importance, assessing issues in cirrhotic patients is frequently neglected. This article provides a comprehensive review of epidemiology, pathophysiology, diagnosis, treatment disturbances cirrhosis. The was conducted using PubMed/Medline, EMBASE, Scielo databases, encompassing 172 articles. Liver associated with disturbances, including diabetes, hypoglycemia, sarcopenia, thyroid dysfunction, hypogonadotropic hypogonadism, bone disease, adrenal insufficiency, growth hormone secondary hyperaldosteronism. optimal tools for diagnosing diabetes detecting hypoglycemia are oral glucose tolerance test continuous monitoring system, respectively. Sarcopenia be assessed through imaging functional tests, while other evaluated hormonal assays studies. Treatment options include metformin, glucagon-like peptide-1 analogs, sodium-glucose co-transporter-2 inhibitors, insulin, which effective safe control. Established standards followed managing replacement therapy often necessary dysfunctions. transplantation address some these problems.

Язык: Английский

---

PPARβ/δ attenuates hepatic fibrosis by reducing SMAD3 phosphorylation and p300 levels via AMPK in hepatic stellate cells

Biomedicine & Pharmacotherapy, Год журнала: 2024, Номер 179, С. 117303 - 117303

Опубликована: Авг. 18, 2024

The role of peroxisome proliferator-activated receptor (PPAR)β/δ in hepatic fibrosis remains a subject debate. Here, we examined the effects PPARβ/δ agonist on pathogenesis liver and activation stellate cells (HSCs), main effector fibrosis, response to pro-fibrotic stimulus transforming growth factor-β (TGF-β). GW501516 completely prevented glucose intolerance peripheral insulin resistance, blocked accumulation collagen liver, attenuated expression inflammatory fibrogenic genes mice fed choline-deficient high-fat diet (CD-HFD). antifibrogenic effect observed livers CD-HFD-fed could occur through an action HSCs since primary isolated from Ppard

Язык: Английский

---

Single-Cell RNA Sequencing Reveals Macrophage Dynamics During MASH in Leptin-Deficient Rats

Cells, Год журнала: 2025, Номер 14(2), С. 96 - 96

Опубликована: Янв. 10, 2025

Macrophages play important roles in metabolic dysfunction-associated steatohepatitis (MASH), an advanced and inflammatory stage of steatotic liver disease (MASLD). In humans mice, the cellular heterogeneity diverse function hepatic macrophages MASH have been investigated by single cell RNA sequencing (scRNA-seq). However, little is known about their rats. Here, we collected tissues at postnatal week 16, when our previously characterized Lep∆I14/∆I14 rats developed phenotypes. By scRNA-seq, found increase number endothelial cells a decrease that NK B cells. Hepatic underwent unique M1 to M2 transition without expression classical markers such as Arg1 Nos2, except for Cd163. Lipid-associated (LAMs) were increased, which could be detected antibody against Cd63. microenvironment, had increased interactions with hepatocytes, myofibroblasts, T cells, neutrophils, dendritic while interaction strengths remained unchanged. Finally, macrophage migration inhibitory factor (MIF) pathway was identified top upregulated cell-communication MASH. conclusion, dissected dynamics during resolution provided fundamental tools investigation rat models.

Язык: Английский

---

The role of liver sinusoidal endothelial cells in metabolic dysfunction-associated steatotic liver diseases and liver cancer: mechanisms and potential therapies

Angiogenesis, Год журнала: 2025, Номер 28(2)

Опубликована: Фев. 3, 2025

Язык: Английский

---

Evaluation of Metabolic Dysfunction-Associated Fatty Liver Disease-Related Pathogenic Mechanisms in Human Steatotic Liver Cell-Based Model: Beneficial Effects of Prunus domestica L. subsp. syriaca Extract

Nutrients, Год журнала: 2025, Номер 17(7), С. 1249 - 1249

Опубликована: Апрель 3, 2025

Background/Objectives: Disrupted glucose uptake, oxidative stress, and increased de novo lipogenesis are some of the key features metabolic dysfunction-associated fatty liver disease (MASLD). The modulation these pathogenic mechanisms using extracts from natural sustainable sources is a promising strategy to mitigate progression. This study aimed evaluate effects Prunus domestica L. subsp. syriaca extract on processes, taking advantage cell-based model steatotic hepatocytes (HepG2-OA) that recapitulates pathophysiological MASLD. Methods: HepG2-OA cell was generated by treating cells for 7 days with 100 μM oleic acid (OA). effect different concentrations (0.01, 0.1, 0.5, 1 mg/mL) P. assessed through MTT assay (cell viability), flow cytometry (glucose uptake reactive oxygen species, ROS, production), spectrophotometry (lipid accumulation), qRT-PCR (expression selected genes). Results: exhibited no cytotoxicity at any tested concentration after 24 48 h in cells. dose-dependent fashion both 6 h. Additionally, reduced lipid accumulation downregulated expression lipogenic genes (DGAT1 FASN). Furthermore, cells, ROS production stress-related (SOD CAT). Conclusions: positively modulated molecular associated metabolism, lipogenesis, supporting its potential as nutraceutical candidate MASLD management.

Язык: Английский

---

Metabolic profiling of tryptophan pathways: Implications for obesity and metabolic dysfunction‐associated steatotic liver disease

European Journal of Clinical Investigation, Год журнала: 2024, Номер 54(11)

Опубликована: Июнь 28, 2024

Abstract Background and Aims The rise in obesity highlights the need for improved therapeutic strategies, particularly addressing metabolic dysfunction‐associated steatotic liver disease (MASLD). We aim to assess role of tryptophan pathways pathogenesis different histological stages MASLD. Materials Methods used ultra‐high performance liquid chromatography quantify circulating levels 15 tryptophan‐related metabolites from kynurenine, indole serotonin pathways. A cohort 76 subjects was analysed, comprising 18 with normal weight 58 morbid obesity, these last being subclassified into (NL), simple steatosis (SS) steatohepatitis (MASH). Then, we conducted gene expression analysis hepatic IDO‐1 kynyrenine‐3‐monooxygenase (KMO). Results Key findings revealed a distinct signature characterized by higher concentration kynurenine‐related metabolites, decrease indole‐3‐acetic acid indole‐3‐propionic acid, an alteration pathway. Elevated were associated MASLD presence (37.659 (32.577–39.823) μM NL subjects; 41.522 (38.803–45.276) patients MASLD). Overall, pathway fluxes demonstrated induction catabolism via SS kynurenine MASH. found decreased KMO compared SS. Conclusions identified distinctive marked changes catabolic pathways, discernible through altered metabolite profiles. observed stage‐specific alterations MASLD, highlighting potential utility targeting interventions.

Язык: Английский

---