Molecular and Cellular Endocrinology最新文献_第2页

PTH-dependent stabilization of RANKL mRNA is associated with increased phosphorylation of the KH-type splicing regulatory protein PTH 依赖性的 RANKL mRNA 稳定与 KH 型剪接调控蛋白的磷酸化增加有关。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-12 DOI: 10.1016/j.mce.2024.112412

Gang-Qing Yao, Meiling Zhu, Karl Insogna

{"title":"PTH-dependent stabilization of RANKL mRNA is associated with increased phosphorylation of the KH-type splicing regulatory protein","authors":"Gang-Qing Yao, Meiling Zhu, Karl Insogna","doi":"10.1016/j.mce.2024.112412","DOIUrl":"10.1016/j.mce.2024.112412","url":null,"abstract":"<div><div>Parathyroid hormone (PTH) receptor agonists promote bone formation but also increase osteoclastogenesis, in part by increasing expression of the receptor activator of nuclear factor kappa-Β ligand (RANKL). In addition to activation of transcription, regulation of mRNA stability is another important molecular mechanism controlling mRNA abundance. PTH treatment for 6 h resulted in a 7.4-fold elevation in RANKL mRNA expression in UAMS-32P cells, despite prior inhibition of cellular transcription by thiophosphoryl (TPL). RANKL mRNA, like other TNF family members, contains AU-Rich Elements (AREs) in the 3’ UTR. AU-Rich Element Binding Proteins (ABPs including KSRP, TTP, AUF1 and HuR) bind to AREs and regulate mRNA stability. There was significantly more KSRP bound to RANKL mRNA than any of the other ABPs. PTH did not increase the amount of ABPs bound to the RANKL transcript. However, the level of cellular phosphorylated KSRP was significantly increased in UAMS-32P cells pre-treated with TPL followed by PTH exposure, compared to cells treated with vehicle following TPL. The extent of phosphorylation of cellular AUF1, HuR, and TTP did not increase with PTH treatment. There were no significant changes in the cellular content of total Pin1 and phospho-Pin1 protein with PTH treatment. We conclude that increases in cellular phospho-KSRP following PTH treatment, together with fact that the total amount of the KSRP bound to the RANKL mRNA did not change with PTH-treatment, may indicate that phospho-KSRP plays some role in stabilizing the RANKL transcript.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112412"},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623965","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

Rapid downregulation of DICER is a hallmark of adipose tissue upon high-fat diet feeding DICER的快速下调是脂肪组织在摄入高脂肪饮食后的一个特征。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-12 DOI: 10.1016/j.mce.2024.112413

Søren Madsen , A. Augusto Peluso , Caio Y. Yonamine , Lars R. Ingerslev , Morten Dall , Patricia S.S. Petersen , Kaja Plucinska , Marta Pradas-Juni , Roger Moreno-Justicia , Alba Gonzalez-Franquesa , Kurt Højlund , Jan-Wilhelm Kornfeld , Brice Emanuelli , Sara G. Vienberg , Jonas T. Treebak

{"title":"Rapid downregulation of DICER is a hallmark of adipose tissue upon high-fat diet feeding","authors":"Søren Madsen , A. Augusto Peluso , Caio Y. Yonamine , Lars R. Ingerslev , Morten Dall , Patricia S.S. Petersen , Kaja Plucinska , Marta Pradas-Juni , Roger Moreno-Justicia , Alba Gonzalez-Franquesa , Kurt Højlund , Jan-Wilhelm Kornfeld , Brice Emanuelli , Sara G. Vienberg , Jonas T. Treebak","doi":"10.1016/j.mce.2024.112413","DOIUrl":"10.1016/j.mce.2024.112413","url":null,"abstract":"<div><div>Adipose tissue regulates whole-body energy balance and is crucial for metabolic health. With energy surplus, adipose tissue expands, which may lead to local areas of hypoxia and inflammation, and consequently impair whole-body insulin sensitivity. We report that DICER, a key enzyme for miRNA maturation, is significantly lower in abdominal subcutaneous white adipose tissue of men with obesity compared with men with a lean phenotype. Furthermore, DICER is profoundly downregulated in mouse adipose tissue and liver within the first week on a high-fat diet (HFD), and remains low after prolonged HFD feeding. Downregulation of DICER in mice occurs in both mature adipocytes and stromal vascular cells. Mechanistically, chemically induced hypoxia <em>in vitro</em> shows DICER degradation via interaction with hypoxia-inducible factor 1-α (HIF1α). Moreover, DICER and HIF1α interact in brown adipose tissue post-HFD which may signal for DICER degradation. Finally, RNA sequencing reveals a striking time-dependent downregulation of total miRNA content in mouse subcutaneous adipose tissue after HFD feeding. Collectively, HFD in mice reduces adipose tissue DICER, likely due to hypoxia-induced interaction with HIF1α during tissue expansion, and this significantly impacts miRNA content.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112413"},"PeriodicalIF":3.8,"publicationDate":"2024-11-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623971","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

Transforming growth factor β-2 is rhythmically expressed in both WT and BMAL1-deficient hypothalamic neurons and regulates neuropeptide Y: Disruption by palmitate 转化生长因子β-2在WT和BMAL1缺陷的下丘脑神经元中均有节律地表达，并调节神经肽Y：棕榈酸酯的干扰。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-08 DOI: 10.1016/j.mce.2024.112411

Aws F. Mustafa , Wenyuan He , Denise D. Belsham

{"title":"Transforming growth factor β-2 is rhythmically expressed in both WT and BMAL1-deficient hypothalamic neurons and regulates neuropeptide Y: Disruption by palmitate","authors":"Aws F. Mustafa , Wenyuan He , Denise D. Belsham","doi":"10.1016/j.mce.2024.112411","DOIUrl":"10.1016/j.mce.2024.112411","url":null,"abstract":"<div><div>The hypothalamus contains neuropeptide Y (NPY)-expressing neurons that control food intake and regulate energy homeostasis. During the development of obesity, neuroinflammation occurs in the hypothalamus before peripheral tissues, but the cytokines involved have not been thoroughly studied. Among them is the transforming growth factor beta (TGF-β) family of cytokines. Herein, we demonstrate that <em>Tgfb 1–3</em>, as well as its receptors <em>Tgfbr1</em> and <em>Tgfbr2</em>, exhibit high levels of expression in the whole hypothalamus, primary hypothalamic culture, and immortalized hypothalamic neurons. Of interest, only <em>Tgfb2</em> mRNA displays circadian expression in the immortalized hypothalamic neurons and maintains this rhythmicity in BMAL1-KO-derived hypothalamic neurons that are deficient of inherent clock gene rhythmicity. Although BMAL2 may serve as an alternative rhythm generation mechanism in the absence of BMAL1, its knockdown did not affect <em>Tgfb2</em> expression. Treatment of immortalized NPY-expressing neurons with TGF-β2 upregulates the core circadian oscillators <em>Bmal1</em> and <em>Nr1d1</em>, and importantly, also <em>Npy</em> mRNA expression. With obesity, the hypothalamus is exposed to elevated levels of palmitate, a saturated fatty acid that promotes neuroinflammation by upregulating pro-inflammatory cytokines. Palmitate treatment disrupts the expression of TGF-β signaling components, increases BMAL1 binding to the <em>Tgfb2</em> 5’ regulatory region, and upregulates <em>Npy</em> mRNA, whereas antagonizing TGFBRI attenuates the upregulation of <em>Npy</em>. These results suggest that hypothalamic neuronal TGF-β2 lies at the intersection of circadian rhythms, feeding neuropeptide control, and neuroinflammation. A better understanding of the underlying mechanisms that link nutrient excess to hypothalamic dysfunction is critical for the development of effective prevention and treatment strategies.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112411"},"PeriodicalIF":3.8,"publicationDate":"2024-11-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623977","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

Puerarin reduces diabetic nephropathy-induced podocyte pyroptosis by modulating the SIRT1/NLRP3/caspase-1 pathway 葛根素通过调节SIRT1/NLRP3/caspase-1途径减少糖尿病肾病诱导的荚膜细胞脓毒症

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-06 DOI: 10.1016/j.mce.2024.112409

Lu Wang , Xiaohai Xie , Qiuyan Chen , Yulin Chen , Xiaohui Xu , Tao Liang

{"title":"Puerarin reduces diabetic nephropathy-induced podocyte pyroptosis by modulating the SIRT1/NLRP3/caspase-1 pathway","authors":"Lu Wang , Xiaohai Xie , Qiuyan Chen , Yulin Chen , Xiaohui Xu , Tao Liang","doi":"10.1016/j.mce.2024.112409","DOIUrl":"10.1016/j.mce.2024.112409","url":null,"abstract":"<div><h3>Background</h3><div>Chronic kidney inflammation and podocyte injury are key pathological features of Diabetic Nephropathy (DN). Puerarin has been shown to inhibit podocyte pyroptosis and provide renal protection, although its molecular mechanism remains unclear.</div></div><div><h3>Methods</h3><div>The effects and mechanisms of puerarin on podocyte pyroptosis were investigated in a DN mouse model. In vivo, a DN model was established using streptozotocin (STZ) and treated with puerarin, a SIRT1 agonist, or a SIRT1 inhibitor. In vitro, a podocyte pyroptosis model was induced under high glucose (HG) conditions, and lentivirus transfection was used to either silence or overexpress SIRT1. Techniques including ELISA, transmission electron microscopy, flow cytometry, PCR, and Western blotting were employed to explore the molecular mechanisms by which puerarin inhibits podocyte pyroptosis.</div></div><div><h3>Results</h3><div>The study showed that SIRT1 expression was significantly downregulated in STZ-induced DN mice and HG-induced MPC-5 cell pyroptosis models. Overexpression of SIRT1 decreased the secretion of inflammatory factors, reduced reactive oxygen species (ROS) release, improved podocyte injury, restored podocyte function, and inhibited the expression of the NLRP3 inflammasome and its downstream factors. Furthermore, puerarin increased SIRT1 expression in DN mice and HG-treated MPC-5 cells, inhibited the activation of the NLRP3/Caspase-1 pathway, reduced podocyte pyroptosis, and alleviated renal inflammatory damage.</div></div><div><h3>Conclusion</h3><div>These findings suggest that puerarin may inhibit podocyte pyroptosis, reduce podocyte injury, and mitigate renal inflammatory damage by modulating the SIRT1/NLRP3/Caspase-1 pathway.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112409"},"PeriodicalIF":3.8,"publicationDate":"2024-11-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142623981","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

Female C57BL/6 mice exhibit protection against nonalcoholic fatty liver disease and diabesity accompanied by differential regulation of hepatic lipocalin prostaglandin D2 synthase 雌性 C57BL/6 小鼠对非酒精性脂肪肝和肥胖症的保护作用伴随着肝脏脂联素前列腺素 D2 合成酶的不同调节。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-04 DOI: 10.1016/j.mce.2024.112404

Md Asrarul Islam , Rhema Khairnar , Joshua Fleishman , Sandra E. Reznik , Louis Ragolia , Shruthi Gobbooru , Sunil Kumar

引用次数: 0

PRDM16 in thermogenic adipocytes mediates an inter-organ protective signaling against alcohol-associated liver disease 发热脂肪细胞中的 PRDM16 介导器官间保护信号，防止酒精相关性肝病。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-04 DOI: 10.1016/j.mce.2024.112407

Shanshan Liu , Kezhou Zhu , Yunying Huang , Weilai Ye , Jun Wu

{"title":"PRDM16 in thermogenic adipocytes mediates an inter-organ protective signaling against alcohol-associated liver disease","authors":"Shanshan Liu , Kezhou Zhu , Yunying Huang , Weilai Ye , Jun Wu","doi":"10.1016/j.mce.2024.112407","DOIUrl":"10.1016/j.mce.2024.112407","url":null,"abstract":"<div><div>Alcohol-associated liver disease (ALD) is one of the major chronic liver diseases and despite the dire clinical needs and extensive research efforts, no effective therapies are available for late-stages of ALD except for liver transplantation. Adipose tissue dysfunction has been implicated in the progression of ALD. Furthermore, it has been previously suggested that thermogenic fat can be activated after alcohol consumption. In this study, increased thermogenic gene expression was detected in both classical brown adipose tissue and beige adipocytes in mice that were given alcohol challenges even when housed at thermoneutrality. In particular, higher expression level of <em>Prdm16</em>, the key transcriptional co-component for beige fat function, was observed in the subcutaneous fat of mice after alcohol challenges. The objective of the present study is to explore the functional significance of adipocyte PRDM16 in the context of ALD. Even though <em>Prdm16</em> adipocyte-specific-deleted mice (<em>Prdm16</em>-adKO) did not show liver defects at the basal level, following two different alcohol challenge regimens, exacerbated ALD phenotypes were observed in <em>Prdm16</em>-adKO mice compared to that of the control <em>Prdm16</em> <sup>fl/fl</sup> mice. Mechanistic investigation suggests that adipose dysfunction after alcohol abuse, including alcohol-induced changes in adipose lipolytic activity, fatty acid oxidation and adipokine levels, may render the worsened ALD phenotype in <em>Prdm16</em>-adKO mice. These results indicate PRDM16-mediated signaling in fat plays a protective role against liver injury caused by alcohol abuse, suggesting it may represent a potential therapeutic target against ALD.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112407"},"PeriodicalIF":3.8,"publicationDate":"2024-11-04","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142591245","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

NLRP3 inhibitor alleviates glycemic variability-induced cognitive impairment in aged rats with type 2 diabetes mellitus NLRP3抑制剂可缓解血糖变化诱发的2型糖尿病老年大鼠认知功能障碍

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-11-01 DOI: 10.1016/j.mce.2024.112406

Wei Yang, Si-Cong Si, Jing Li, Yi-Xin Ma, Huan Zhao, Jia Liu

{"title":"NLRP3 inhibitor alleviates glycemic variability-induced cognitive impairment in aged rats with type 2 diabetes mellitus","authors":"Wei Yang, Si-Cong Si, Jing Li, Yi-Xin Ma, Huan Zhao, Jia Liu","doi":"10.1016/j.mce.2024.112406","DOIUrl":"10.1016/j.mce.2024.112406","url":null,"abstract":"<div><div>Glycemic variability (GV) markedly exacerbates cognitive impairment in elderly patients with type 2 diabetes mellitus (T2DM), in part through chronic inflammation. This study investigated the therapeutic efficacy of the NLRP3 inflammasome inhibitor MCC950 in mitigating GV-induced cognitive impairment in an aged rat model of T2DM. Aged Sprague-Dawley rats with induced T2DM were subjected to GV conditions, and the effects of MCC950 were evaluated through measurement of body weight, blood glucose, lipid profiles, insulin level, inflammatory markers, and cognitive function. Transcriptomic analysis was performed on the hippocampus and prefrontal cortex. Treatment with MCC950 significantly alleviated weight loss and hyperglycemia in the GV group compared with the control group. MCC950 also reduced the levels of cholesterol, triglycerides, and pro-inflammatory markers (interleukin-1β (IL-1β) and interleukin-18 (IL-18)). Most notably, MCC950 improved spatial learning and memory retention in the GV group. Immunohistochemical analysis indicated a reduction in inflammasome activation and an increase in the expression level of the neuronal marker NeuN in the hippocampus. Transcriptomic analysis revealed that MCC950 altered neuroactive ligand-receptor interaction pathways in the hippocampus and influenced receptor binding and cell adhesion processes in the prefrontal cortex. These findings validated the efficacy of NLRP3 inhibitor in mitigating GV-induced cognitive impairment in elderly rats with T2DM and provided the basis for subsequent clinical studies exploring the broader potential of NLRP3-targeted interventions in addressing diabetes-associated cognitive impairment.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112406"},"PeriodicalIF":3.8,"publicationDate":"2024-11-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142567917","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

Status of sperm mitochondrial functions and DNA methylation in infertile men with clinical varicocele before and after treatment 临床精索静脉曲张不育男性精子线粒体功能和 DNA 甲基化治疗前后的状况。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-10-30 DOI: 10.1016/j.mce.2024.112393

Deepshikha Arya , Prakash Pawar , Rahul Gajbhiye , Deepti Tandon , Priyank Kothari , Reshma Goankar , Dipty Singh

{"title":"Status of sperm mitochondrial functions and DNA methylation in infertile men with clinical varicocele before and after treatment","authors":"Deepshikha Arya , Prakash Pawar , Rahul Gajbhiye , Deepti Tandon , Priyank Kothari , Reshma Goankar , Dipty Singh","doi":"10.1016/j.mce.2024.112393","DOIUrl":"10.1016/j.mce.2024.112393","url":null,"abstract":"<div><div>Varicocele has been associated with reduced male fertility potential. Treatment modalities for varicocele improve semen parameters, yet more than 50% of cases remain infertile. Varicocele-induced heat and hypoxia stress may affect sperm mitochondrial functions, possibly leading to aberrant epigenetic modifications. This study includes 30 fertile men and 40 infertile men with clinical varicocele. The effect of varicocele treatment (antioxidant supplementation and or varicocelectomy) was evaluated after 3 months of treatment. Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (iROS) were measured by flow cytometry using JC-1 and DCFDA, respectively. mtDNA copy number and deletions were determined by PCR. DNA methylation was analysed by pyrosequencing. Present investigations suggest that infertile men with varicocele have abnormal semen parameters; significantly low MMP, high iROS, and high mtDNA copy number. Semen parameters were improved in a subset of men of both the treatment modalities; however, it was noted that varicocelectomy helped better in improving sperm parameters compared to antioxidant treatment. Both treatment modalities helped in reducing iROS and mtDNA copy number significantly; however, they were noneffective in improving MMP. Altered DNA methylation at mitochondria <em>D loop</em> and mitochondrial structure and function genes <em>UQCRC2</em>, <em>MIC60</em>, <em>TOM22,</em> and <em>LETM1</em> (promoter region) were observed in varicocele group. The DNA methylation levels were restored after varicocele treatment; however, the restoration was not consistent at all CpG sites. Both the treatment modalities helped in restoring the altered DNA methylation levels of mitochondrial genes but the restoration is nonhomogeneous across the studied CpG sites.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112393"},"PeriodicalIF":3.8,"publicationDate":"2024-10-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558260","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

An optimized fractionation method reveals insulin-induced membrane surface localization of GLUT1 to increase glycolysis in LβT2 cells 优化的分馏方法揭示了胰岛素诱导的 GLUT1 膜表面定位增加 LβT2 细胞中的糖酵解。

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-10-29 DOI: 10.1016/j.mce.2024.112405

Olivia Molinar-Inglis , Kiara Wiggins , Anjali Varma , Zena Del Mundo , Jose M. Adame , Alyssa Cozzo , Oscar Muñoz , Uyen-Vy Le , Davina Trinh , Alexis C. Garcia , Metztli Cisneros-Aguirre , Monica L. Gonzalez Ramirez , Jeremiah Keyes , Jin Zhang , Mark A. Lawson , JoAnn Trejo , Dequina A. Nicholas

{"title":"An optimized fractionation method reveals insulin-induced membrane surface localization of GLUT1 to increase glycolysis in LβT2 cells","authors":"Olivia Molinar-Inglis , Kiara Wiggins , Anjali Varma , Zena Del Mundo , Jose M. Adame , Alyssa Cozzo , Oscar Muñoz , Uyen-Vy Le , Davina Trinh , Alexis C. Garcia , Metztli Cisneros-Aguirre , Monica L. Gonzalez Ramirez , Jeremiah Keyes , Jin Zhang , Mark A. Lawson , JoAnn Trejo , Dequina A. Nicholas","doi":"10.1016/j.mce.2024.112405","DOIUrl":"10.1016/j.mce.2024.112405","url":null,"abstract":"<div><div>Insulin is an important regulator of whole-body glucose homeostasis. In insulin sensitive tissues such as muscle and adipose, insulin induces the translocation of glucose transporter 4 (GLUT4) to the cell membrane, thereby increasing glucose uptake. However, insulin also signals in tissues that are not generally associated with glucose homeostasis. In the human reproductive endocrine axis, hyperinsulinemia suppresses the secretion of gonadotropins from gonadotrope cells of the anterior pituitary, thereby linking insulin dysregulation to suboptimal reproductive health. In the mouse, gonadotropes express the insulin receptor which has the canonical signaling response of IRS, AKT, and mTOR activation. However, the functional outcomes of insulin action on gonadotropes are unclear. Here, we demonstrate through use of an optimized cell fractionation protocol that insulin stimulation of the LβT2 gonadotropic cell line results in the unexpected translocation of GLUT1 to the plasma membrane. Using our high purity fractionation protocol, we further demonstrate that though Akt signaling in response to insulin is intact, insulin-induced translocation of GLUT1 occurs independently of Akt activation in LβT2 cells.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112405"},"PeriodicalIF":3.8,"publicationDate":"2024-10-29","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142558259","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

FSH increases lipid droplet content by regulating the expression of genes related to lipid storage in Rat Sertoli cells FSH 通过调节大鼠 Sertoli 细胞中脂质储存相关基因的表达增加脂滴含量

IF 3.8 3区医学

Molecular and Cellular Endocrinology Pub Date : 2024-10-28 DOI: 10.1016/j.mce.2024.112403

Marina Ercilia Dasso, Cecilia Lucia Centola, Maria Noel Galardo, Maria Fernanda Riera, Silvina Beatriz Meroni

{"title":"FSH increases lipid droplet content by regulating the expression of genes related to lipid storage in Rat Sertoli cells","authors":"Marina Ercilia Dasso, Cecilia Lucia Centola, Maria Noel Galardo, Maria Fernanda Riera, Silvina Beatriz Meroni","doi":"10.1016/j.mce.2024.112403","DOIUrl":"10.1016/j.mce.2024.112403","url":null,"abstract":"<div><div>Sertoli cells (SCs) are essential for appropriate spermatogenesis. From a metabolic standpoint, they catabolize glucose and provide germ cells with lactate, which is their main energy source. SCs also oxidize fatty acids (FAs), which are stored as triacylglycerides (TAGs) within lipid droplets (LDs), to fulfill their own energy requirements. On the other hand, it has been demonstrated that FSH regulates some of SCs functions, but little is known about its effect on lipid metabolism. In the present study, we aimed to analyze FSH-mediated regulation of (1) lipid storage in LDs and (2) the expression of genes involved in FAs activation and TAG synthesis and storage in SCs. SCs obtained from 20-day-old rats were cultured for different incubation periods with FSH (100 ng/ml). It was observed that FSH increased LD content and TAG levels in SCs. There were also increments in the expression of <em>Plin1, Fabp5, Acsl1, Acsl4, Gpat3</em>, and <em>Dgat1</em>, which suggests that these proteins may mediate the increase in TAGs and LDs elicited by FSH. Regarding the signaling involved in FSH actions, it was observed that dbcAMP increased LD, and H89, a PKA inhibitor, inhibited FSH stimulus. Also, dbcAMP increased P<em>lin2, Fabp5, Acsl1, Acsl4, and Dgat1</em> mRNA levels, confirming a role of the cAMP/PKA pathway in the regulation of lipid storage in SCs. Altogether, these results suggest that FSH, via the cAMP/PKA pathway, regulates lipid storage in SCs ensuring the availability of substrates to satisfy their energy requirements.</div></div>","PeriodicalId":18707,"journal":{"name":"Molecular and Cellular Endocrinology","volume":"595 ","pages":"Article 112403"},"PeriodicalIF":3.8,"publicationDate":"2024-10-28","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142553009","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