Molecular and Cellular Endocrinology最新文献

英文中文

Obesity prevention by different exercise protocols (HIIT or MICT) involves beige adipocyte recruitment and improved mitochondrial dynamics in high-fat-fed mice

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-27 DOI: 10.1016/j.mce.2025.112533

Daiana Araujo Santana-Oliveira , Henrique Souza-Tavares , Aline Fernandes-da-Silva , Thatiany Souza Marinho , Flavia Maria Silva-Veiga , Julio Beltrame Daleprane , Vanessa Souza-Mello

Aim

This study evaluated the effects of high-intensity interval training (HIIT) and moderate-intensity continuous training (MICT) on UCP1-dependent and UCP1-independent thermogenic and mitochondrial dynamics markers in the inguinal sWAT of high-fat-fed mice.

Methods

Sixty male C57BL/6 mice (3 months old) were divided into six experimental groups: control diet (C), C + HIIT (C-HIIT), C + MICT (C-MICT), high-fat diet (HF), HF + HIIT (HF-HIIT) and HF + MICT (HF-MICT). The diet and exercise protocols started simultaneously and lasted ten weeks.

Results

HIIT and MICT prevented body mass gain and fat pad expansion, improved insulin sensitivity, and induced browning in C-fed and HF-fed animals. Chronic intake of a HF diet caused adipocyte hypertrophy with a proinflammatory adipokine profile and impaired the expression of thermogenic and mitochondrial dynamics markers. However, both exercise intensities increased anti-inflammatory adipokine concentrations and improved gene markers of mitochondrial dynamics, resulting in sustained UCP1-dependent and UCP1-independent thermogenic markers and maintenance of the beige phenotype in inguinal sWAT. The principal component analysis placed all trained groups opposite the HF group and near the C group, ensuring the effectiveness of HIIT and MICT to prevent metabolic alterations.

Conclusions

This study provides reliable evidence that, regardless of intensity, exercise is a strategy to prevent obesity by reducing body fat accumulation and inducing browning. The anti-inflammatory adipokine profile and the increased expression of UCP1-dependent and UCP1-independent thermogenic markers sustained active beige adipocytes and mitochondrial enhancement to halt metabolic disturbances due to HF-feeding in exercised mice.

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引用次数: 0

An endocrinological perspective on polycystic ovarian syndrome

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-25 DOI: 10.1016/j.mce.2025.112524

Smarto Basak , Amit Kumar Dixit , Ranjit Kumar Dey , Lalrin Puia , Manajit Bora , Sanjay Kumar Y.R. , Gajji Babu

Polycystic ovarian syndrome (PCOS) is a complex endocrinological disorder that involves dysfunctions across multiple endocrine axes, including the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes. Our review focuses on understanding the pathophysiology of PCOS through an endocrinological perspective, emphasizing the complex interactions between multiple endocrine axes. We have discussed the roles of the HPG, HPA, and HPT axes in PCOS. Dysregulation of the HPG axis, particularly the altered gonadotropin-releasing hormone pulse frequency resulting in elevated ratio of luteinizing hormone to follicle stimulating hormone, is central to the hyperandrogenism and anovulation, observed in PCOS. We have further highlighted the contributions of the HPA and HPT axes, where elevated adrenal androgen levels and hypothyroidism intensifies the phenotypes of PCOS. Additionally, insulin resistance and hyperinsulinemia, commonly associated with PCOS, aggravates hormonal disturbances and heighten the risk of metabolic complications such as type 2 diabetes and cardiovascular diseases. Elevated levels of anti-Müllerian hormone have also been emphasized as a key factor in inhibiting follicular growth, leading to impaired ovarian function and hyperandrogenism. This review further supports that PCOS is a multifactorial condition involving complex feedback mechanisms between the endocrine, metabolic, and reproductive systems. Furthermore, there remains a huge scope for deciphering the precise molecular interactions between the HPG, HPA, and HPT axes in PCOS, which could pave the way for targeted therapies for better management of both the endocrine and metabolic aspects of this disorder. This review will benefit researchers to get an endocrine perspective on PCOS.

{"title":"An endocrinological perspective on polycystic ovarian syndrome","authors":"Smarto Basak , Amit Kumar Dixit , Ranjit Kumar Dey , Lalrin Puia , Manajit Bora , Sanjay Kumar Y.R. , Gajji Babu","doi":"10.1016/j.mce.2025.112524","DOIUrl":"10.1016/j.mce.2025.112524","url":null,"abstract":"<div><div>Polycystic ovarian syndrome (PCOS) is a complex endocrinological disorder that involves dysfunctions across multiple endocrine axes, including the hypothalamic-pituitary-gonadal (HPG), hypothalamic-pituitary-adrenal (HPA) and hypothalamic-pituitary-thyroid (HPT) axes. Our review focuses on understanding the pathophysiology of PCOS through an endocrinological perspective, emphasizing the complex interactions between multiple endocrine axes. We have discussed the roles of the HPG, HPA, and HPT axes in PCOS. Dysregulation of the HPG axis, particularly the altered gonadotropin-releasing hormone pulse frequency resulting in elevated ratio of luteinizing hormone to follicle stimulating hormone, is central to the hyperandrogenism and anovulation, observed in PCOS. We have further highlighted the contributions of the HPA and HPT axes, where elevated adrenal androgen levels and hypothyroidism intensifies the phenotypes of PCOS. Additionally, insulin resistance and hyperinsulinemia, commonly associated with PCOS, aggravates hormonal disturbances and heighten the risk of metabolic complications such as type 2 diabetes and cardiovascular diseases. Elevated levels of anti-Müllerian hormone have also been emphasized as a key factor in inhibiting follicular growth, leading to impaired ovarian function and hyperandrogenism. This review further supports that PCOS is a multifactorial condition involving complex feedback mechanisms between the endocrine, metabolic, and reproductive systems. Furthermore, there remains a huge scope for deciphering the precise molecular interactions between the HPG, HPA, and HPT axes in PCOS, which could pave the way for targeted therapies for better management of both the endocrine and metabolic aspects of this disorder. This review will benefit researchers to get an endocrine perspective on PCOS.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"602 ","pages":"Article 112524"},"PeriodicalIF":3.8,"publicationDate":"2025-03-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143730675","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring the functional, protective, and transcriptomic effects of GIP on cytokine-exposed human pancreatic islets and EndoC-βH5 cells 探索 GIP 对细胞因子暴露的人类胰岛和 EndoC-βH5 细胞的功能性、保护性和转录组学效应。

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-21 DOI: 10.1016/j.mce.2025.112522

Kristine Henriksen , Anne Jørgensen , Simranjeet Kaur , Rebekka Gerwig , Cecilie Amalie Brøgger Svane , Filip K. Knop , Joachim Størling

Immune-mediated beta-cell destruction and lack of alpha-cell responsiveness to hypoglycaemia are hallmarks of type 1 diabetes pathology. The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may hold therapeutic potential for type 1 diabetes due to its insulinotropic and glucagonotropic effects, as well as its cytoprotective effects shown in rodent beta cells. To further increase our understanding of GIP's effects on human beta cells, we here examined the functional, protective, and transcriptomic effects of GIP in human EndoC-βH5 beta cells and isolated human islets in the presence or absence of proinflammatory cytokines (interferon (IFN)-γ ± interleukin (IL)-1β) as a mimic of type 1 diabetes.

GIP dose-dependently augmented glucose-stimulated insulin secretion from EndoC-βH5 cells and increased insulin and glucagon secretion from human islets at high and low glucose concentrations, respectively. The insulinotropic effect of GIP in EndoC-βH5 cells was abrogated by KN-93, an inhibitor of calcium/calmodulin-dependent protein kinase 2 (CaMK2). GIP did not prevent cytokine-induced apoptosis in EndoC-βH5 cells or human islets, and GIP did not protect against cytokine-induced functional impairment in EndoC-βH5 cells. GIP treatment of human islets for 24 h had no effects on the transcriptome and did not modulate cytokine-induced transcriptional changes. However, GIP augmented IL-1β + IFNγ-induced secretion of interleukin (IL)-10 and c-c motif chemokine ligand (CCL)-2 from human islets while decreasing the secretion of c-x-c motif chemokine ligand (CXCL)-8. In EndoC-βH5 cells, GIP reduced IFN-γ-induced secretion of tumor necrosis factor (TNF)-α, IL-2, IL-6, and IL-10 but increased the secretion of CXCL8, CCL2, CCL4, and CCL11.

In conclusion, our results suggest that the insulinotropic effect of GIP is CaMK2-dependent. Furthermore, our findings indicate that GIP neither exerts cytoprotective effects against cytokines nor modulate the transcriptome of human islets. GIP may, however, exert selective modulatory effects on secreted inflammatory factors from cytokine-exposed beta cells and islets.

{"title":"Exploring the functional, protective, and transcriptomic effects of GIP on cytokine-exposed human pancreatic islets and EndoC-βH5 cells","authors":"Kristine Henriksen , Anne Jørgensen , Simranjeet Kaur , Rebekka Gerwig , Cecilie Amalie Brøgger Svane , Filip K. Knop , Joachim Størling","doi":"10.1016/j.mce.2025.112522","DOIUrl":"10.1016/j.mce.2025.112522","url":null,"abstract":"<div><div>Immune-mediated beta-cell destruction and lack of alpha-cell responsiveness to hypoglycaemia are hallmarks of type 1 diabetes pathology. The incretin hormone glucose-dependent insulinotropic polypeptide (GIP) may hold therapeutic potential for type 1 diabetes due to its insulinotropic and glucagonotropic effects, as well as its cytoprotective effects shown in rodent beta cells. To further increase our understanding of GIP's effects on human beta cells, we here examined the functional, protective, and transcriptomic effects of GIP in human EndoC-βH5 beta cells and isolated human islets in the presence or absence of proinflammatory cytokines (interferon (IFN)-γ ± interleukin (IL)-1β) as a mimic of type 1 diabetes.</div><div>GIP dose-dependently augmented glucose-stimulated insulin secretion from EndoC-βH5 cells and increased insulin and glucagon secretion from human islets at high and low glucose concentrations, respectively. The insulinotropic effect of GIP in EndoC-βH5 cells was abrogated by KN-93, an inhibitor of calcium/calmodulin-dependent protein kinase 2 (CaMK2). GIP did not prevent cytokine-induced apoptosis in EndoC-βH5 cells or human islets, and GIP did not protect against cytokine-induced functional impairment in EndoC-βH5 cells. GIP treatment of human islets for 24 h had no effects on the transcriptome and did not modulate cytokine-induced transcriptional changes. However, GIP augmented IL-1β + IFNγ-induced secretion of interleukin (IL)-10 and c-c motif chemokine ligand (CCL)-2 from human islets while decreasing the secretion of c-x-c motif chemokine ligand (CXCL)-8. In EndoC-βH5 cells, GIP reduced IFN-γ-induced secretion of tumor necrosis factor (TNF)-α, IL-2, IL-6, and IL-10 but increased the secretion of CXCL8, CCL2, CCL4, and CCL11.</div><div>In conclusion, our results suggest that the insulinotropic effect of GIP is CaMK2-dependent. Furthermore, our findings indicate that GIP neither exerts cytoprotective effects against cytokines nor modulate the transcriptome of human islets. GIP may, however, exert selective modulatory effects on secreted inflammatory factors from cytokine-exposed beta cells and islets.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"602 ","pages":"Article 112522"},"PeriodicalIF":3.8,"publicationDate":"2025-03-21","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143691751","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Donepezil alleviates hepatic steatosis by mitigating ER stress via the AMPK/autophagy pathway

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-19 DOI: 10.1016/j.mce.2025.112523

Wonjun Cho , Sung Woo Choi , Do Su Lim , Hyeon Ji Gwon , A.M. Abd El-Aty , Hacı Ahmet Aydemir , Soon Auck Hong , Ji Hoon Jeong , Tae Woo Jung

Donepezil (Do), a drug known for its ability to reduce neuronal inflammation and for its use in the treatment of Alzheimer's disease, has shown promise in combating hepatic lipid accumulation in hyperlipidemic conditions and endoplasmic reticulum (ER) stress, a factor associated with alterations in hepatic lipid metabolism. However, the mechanisms by which these problems are alleviated have not been fully elucidated. In this study, we investigated the effects of Do on hepatic lipid metabolism through both in vitro and in vivo studies. We examined the expression of proteins associated with lipogenesis and ER stress via immunoblot analysis, and hepatic lipid accumulation was assessed via oil red O staining. In addition, autophagosome formation was analyzed by counting MDC-positive cells. Our results demonstrated that Do treatment improved hepatic lipid metabolism and reduced the expression of ER stress markers, resulting in decreased lipogenic lipid deposition and apoptosis in the hepatocytes and livers of hyperlipidemic mice. Mechanistically, knocking down AMPK or inhibiting autophagy with 3-methyladenine (3 MA) attenuated the effects of Do on palmitate-exposed hepatocytes. These results suggest that Do alleviates hepatic ER stress via the AMPK/autophagy pathway and AMPK-mediated fatty acid oxidation, resulting in improved hepatic lipid metabolism and reduced hepatic steatosis and apoptosis. Our study provides evidence that Do may be a promising therapeutic approach for Alzheimer's disease patients with metabolic dysfunction-associated steatotic liver disease (MASLD).

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引用次数: 0

Sexual dimorphisms in endocrinopathies: Their impact on the evolution of metabolic diseases

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-15 DOI: 10.1016/j.mce.2025.112521

Chitralekha Kataki

Sexual dimorphisms, the biological differences between males and females, are well-documented across various endocrine disorders. These dimorphisms not only influence the presentation and progression of endocrinopathies but also play a critical role in the development and evolution of metabolic diseases. This review explores the intricate relationship between sexual dimorphisms and endocrinopathies such as Diabetes Mellitus, Thyroid disorder, Cushing's syndrome, Addison's disease, polycystic ovary syndrome (PCOS), Hypogonadism in males and acromegaly, and their subsequent effects on metabolic dysfunctions like insulin resistance, obesity, and cardiovascular diseases. By examining the hormonal, genetic, and environmental factors underlying these gender-specific differences, we aim to elucidate how sexual dimorphisms contribute to the disparate prevalence, clinical outcomes, and treatment responses observed in metabolic disorders. This review highlights the significance of considering sexual dimorphisms in advancing the understanding of metabolic diseases.

引用次数: 0

cFos-mediated β-Arrestin1 in the RVLM alleviates sympathetic hyperactivity induced by ovariectomy

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-15 DOI: 10.1016/j.mce.2025.112520

Jiuqiong Yan , Qi Meng , Fan Hao , Mingjuan Xu

Sympathetic hyperactivity is a key feature of cardiovascular dysfunction in postmenopausal women and is closely linked to the onset, progression, and outcomes of cardiovascular events. However, the mechanisms underlying sympathetic nerve hyperactivity due to menopause remain unclear. β-arrestin is a versatile class of intracellular proteins that were initially discovered for their ability to disrupt the G protein-coupled receptors (GPCRs) signaling by binding to activated receptors. A notable reduction in the expression of β-arrestin1 in the rostral ventrolateral medulla (RVLM) associated with increased sympathetic activity and elevated blood pressure (BP) in spontaneously hypertensive rats. It has been reported that the cellular oncogene fos (cFos), as a transcription factor, plays a crucial role in BP regulation. This study aimed to investigate whether β-arrestin1, regulated by cFos in the RVLM, contributes to sympathetic hyperactivity induced by menopause. Bilateral ovariectomy (OVX) was performed to establish a postmenopausal rat model. We found that the expression of β-arrestin1 in the RVLM of OVX rats was reduced, whereas estrogen supplementation increased the expression of β-arrestin1. Furthermore, overexpression of β-arrestin1 in the RVLM of OVX rats attenuated the sympathetic hyperactivity. Conversely, reducing β-arrestin1 expression in the RVLM compromised the cardioprotective effects of estrogen in OVX rats. Additionally, inhibiting the expression of the transcription factor cFos in the RVLM of OVX rats diminished the estrogen-induced increase in the expression of β-arrestin1. These findings suggest that estrogen enhances the expression of β-arrestin1 mediated by cFos in the RVLM of OVX rats, thereby alleviating sympathetic nerve hyperactivity and hypertension.

{"title":"cFos-mediated β-Arrestin1 in the RVLM alleviates sympathetic hyperactivity induced by ovariectomy","authors":"Jiuqiong Yan , Qi Meng , Fan Hao , Mingjuan Xu","doi":"10.1016/j.mce.2025.112520","DOIUrl":"10.1016/j.mce.2025.112520","url":null,"abstract":"<div><div>Sympathetic hyperactivity is a key feature of cardiovascular dysfunction in postmenopausal women and is closely linked to the onset, progression, and outcomes of cardiovascular events. However, the mechanisms underlying sympathetic nerve hyperactivity due to menopause remain unclear. β-arrestin is a versatile class of intracellular proteins that were initially discovered for their ability to disrupt the G protein-coupled receptors (GPCRs) signaling by binding to activated receptors. A notable reduction in the expression of β-arrestin1 in the rostral ventrolateral medulla (RVLM) associated with increased sympathetic activity and elevated blood pressure (BP) in spontaneously hypertensive rats. It has been reported that the cellular oncogene fos (cFos), as a transcription factor, plays a crucial role in BP regulation. This study aimed to investigate whether β-arrestin1, regulated by cFos in the RVLM, contributes to sympathetic hyperactivity induced by menopause. Bilateral ovariectomy (OVX) was performed to establish a postmenopausal rat model. We found that the expression of β-arrestin1 in the RVLM of OVX rats was reduced, whereas estrogen supplementation increased the expression of β-arrestin1. Furthermore, overexpression of β-arrestin1 in the RVLM of OVX rats attenuated the sympathetic hyperactivity. Conversely, reducing β-arrestin1 expression in the RVLM compromised the cardioprotective effects of estrogen in OVX rats. Additionally, inhibiting the expression of the transcription factor cFos in the RVLM of OVX rats diminished the estrogen-induced increase in the expression of β-arrestin1. These findings suggest that estrogen enhances the expression of β-arrestin1 mediated by cFos in the RVLM of OVX rats, thereby alleviating sympathetic nerve hyperactivity and hypertension.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112520"},"PeriodicalIF":3.8,"publicationDate":"2025-03-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143649355","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

New perspectives about the article “Dual inhibition of AKT and ERK1/2 pathways restores the expression of progesterone Receptor-B in endometriotic lesions through epigenetic mechanisms"

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-11 DOI: 10.1016/j.mce.2025.112496

Sudipta Dutta , JeHoon Lee , Sakhila K. Banu, Joe A. Arosh

引用次数: 0

Antioxidants improve the viability of diabetic bone marrow MSCs without rescuing their pro-regenerative secretome function

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-06 DOI: 10.1016/j.mce.2025.112519

Michelle Maartens , Mare Vlok , Mari van de Vyver

Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lep^ob/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.

{"title":"Antioxidants improve the viability of diabetic bone marrow MSCs without rescuing their pro-regenerative secretome function","authors":"Michelle Maartens , Mare Vlok , Mari van de Vyver","doi":"10.1016/j.mce.2025.112519","DOIUrl":"10.1016/j.mce.2025.112519","url":null,"abstract":"<div><div>Bone marrow mesenchymal stem cell (BM-MSC) dysfunction and poor viability are prominent in diabetes and limit their therapeutic efficacy. A proteomic investigation was performed to assess disease associated alterations and the efficacy of antioxidants to rescue cellular function. BM-MSCs were isolated from obese diabetic mice (B6.Cg-Lep<sup>ob</sup>/J) cultured in the presence or absence of N-acetylcysteine (NAC) and ascorbic acid-2phosphate (AAP). Label free Liquid Chromatography and Mass Spectrometry (LC-MS) analysis detected 5079 proteins with 251 being differentially expressed between treatment groups. NAC/AAP improved cellular growth/viability post isolation by up-regulating proteins involved in redox status, ATP synthesis, Rho-GTPase signaling and modulated the immunophenotype of BM-MSCs. Despite a single application of the secretome not providing any advantage for wound bed regeneration in full thickness excisional diabetic wounds, the intracellular proteome illustrated the potential mechanisms of action by which NAC/AAP targeted the respiratory chain and modulated the immune phenotype of BM-MSCs. Given these observations, antioxidant supplementation might be more effective as prophylactic strategy to protect MSCs against functional decline instead of using it as a restorative agent and warrants further investigation.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"601 ","pages":"Article 112519"},"PeriodicalIF":3.8,"publicationDate":"2025-03-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143578634","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

引用次数: 0

Exploring different mechanisms of reactive oxygen species formation in hypoxic conditions at the hippocampal CA3 area

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-05 DOI: 10.1016/j.mce.2025.112517

João L. Alves , Rosa M. Quinta-Ferreira , M. Emília Quinta-Ferreira , Carlos M. Matias

Hypoxia can lead to severe consequences for brain function, particularly in regions with high metabolic demands such as the hippocampus. Excessive production of reactive oxygen species (ROS) during hypoxia can initiate a cascade of oxidative stress, evoking cellular damage and neuronal dysfunction. Most of the studies characterizing the formation of ROS are performed in the context of ischemia induced by oxygen-glucose deprivation, thus, the role of hypoxia in less severe conditions requires further clarification. The aim of this work was to identify the major mechanisms of ROS generation and assess flavoprotein autofluorescence changes. For ROS detection, the slices were incubated with the indicator H₂DCFDA, while intrinsic FAD-linked autofluorescence was recorded from indicator free slices. All signals were measured under hypoxia, at the hippocampal mossy fiber synapses of CA3 area, which were chemically stimulated using 20 mM KCl. The results suggest that ROS is formed in the mitochondria, during moderate hypoxia. The blockage of mitochondrial complexes I, III and IV with rotenone, myxothiazol and sodium azide, respectively, and of the mitochondrial calcium uniporter with Ru265, led to the abolishment of ROS changes and to an increase of FAD-linked autofluorescence (with the exception of the complexes III and IV). The blockage of the enzyme oxidases NADPH and xanthine oxidase also impaired ROS formation and rose FAD-linked autofluorescence. Thus, the blockage of any of the steps of the process of ROS formation, namely the activation of critical MRC complexes, calcium entry into the mitochondria, or enzyme oxidases activity, ceases the production of ROS.

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引用次数: 0

The spleen-liver axis supports obesity-induced systemic and fatty liver inflammation via MDSC and NKT cell enrichment

IF 3.8 3区医学 Q2 CELL BIOLOGY

Molecular and Cellular Endocrinology

Pub Date : 2025-03-05 DOI: 10.1016/j.mce.2025.112518

Christina Brummer , Katrin Singer , Kathrin Renner , Christina Bruss , Claus Hellerbrand , Christoph Dorn , Simone Reichelt-Wurm , Wolfram Gronwald , Tobias Pukrop , Wolfgang Herr , Miriam Banas , Marina Kreutz

Obesity promotes adipose tissue inflammation and leads to impaired local but also systemic immune cell homeostasis. This chronic low-grade inflammation plays a significant role in the development of obesity-associated secondary diseases such as metabolic associated fatty liver disease or cancer. The spleen as the central organ of immune cell regulation is anatomically directly connected to the visceral adipose tissue and the liver via the portal vein circulation. However, the inter-organ crosstalk and linkage between obesity-induced systemic, hepatic and splenic immune cell dysregulation is not clearly outlined. In this study blood, spleen, and liver immune cells of non-obese wildtype vs. leptin deficient obese BTBR mice were isolated and analyzed in terms of leukocyte composition by flow cytometry. Significant differences between circulating, spleen- and liver-resident immune cell distribution revealed, that obesity-induced hepatic and systemic immune cell dysregulation is distinct from splenic immune cell reprogramming. Fatty liver inflammation was associated with splenic myeloid derived suppressor cell (MDSC) and natural killer T cell (NKT) enrichment whereas loss of hepatic T and B cells was not reflected by the splenic lymphocyte landscape. Correlation analysis confirmed a selective strong positive correlation between spleen and liver MDSC and NKT cell distribution indicating that the spleen-liver axis modulates obesity-induced immune dysregulation in a cell-specific manner. Similar results were observed in a diet-induced obesity mouse model. These data provide novel insights into the role of the spleen-liver axis in obesity-induced inflammation and foster the understanding of obesity-associated complications such as fatty liver disease and cancer.

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