Metabolism: clinical and experimental最新文献

{"title":"Association of fatty liver index with sudden cardiac arrest in young adults","authors":"Joo Hee Jeong ,&nbsp;Yun Gi Kim ,&nbsp;Kyung-Do Han ,&nbsp;Seung-Young Roh ,&nbsp;Hyoung Seok Lee ,&nbsp;Yun Young Choi ,&nbsp;Sun Young Yim ,&nbsp;Jaemin Shim ,&nbsp;Young-Hoon Kim ,&nbsp;Jong-Il Choi","doi":"10.1016/j.metabol.2024.155981","DOIUrl":"10.1016/j.metabol.2024.155981","url":null,"abstract":"<div><h3>Background</h3><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) contributes to cardiovascular events. Therefore, we aimed to identify the association of MASLD, as indicated by the fatty liver index (FLI), on sudden cardiac arrest (SCA) in young adults.</p></div><div><h3>Methods</h3><p>We analyzed data from adults aged 20–39 years, who underwent health examinations between 2009 and 2012, sourced from the Korean National Health Insurance Service database. The presence of MASLD was determined using the FLI, which was calculated based on an individual's body mass index, waist circumference, gamma-glutamyl transferase and triglyceride levels. The primary outcome was the occurrence of SCA during the follow-up period, until December 2020.</p></div><div><h3>Results</h3><p>Of the total 5,398,082 individuals analyzed, 4,021,056 (74.5 %) had a normal FLI (FLI &lt;30), 837,943 (15.5 %) were within the intermediate range (30–60), and 539,083 (10.0 %) demonstrated a high FLI (≥60). Individuals with a high FLI were older, and comprised a higher proportion of men with hypertension, diabetes mellitus, dyslipidemia, heart failure, and myocardial infarction. During follow-up, SCA occurred in 4255 individuals (0.08 %). The group with a high FLI exhibited an increased incidence (incidence rate, 0.19) and elevated risk of SCA (hazard ratio, 3.04). Adjustment of covariates revealed a 55 % increased risk of SCA in the high FLI group (adjusted hazard ratio 1.55, 95 % confidence interval 1.41–1.70, <em>p</em> &lt; 0.001). Moreover, the influence of a high FLI on SCA risk was more pronounced in women compared to men. Additionally, an increase in relevant cardiometabolic conditions was associated with an elevated risk of SCA.</p></div><div><h3>Conclusions</h3><p>Among young adults, a high risk of MASLD, as indicated by the FLI, revealed an increased risk of SCA. Furthermore, the association of FLI with the risk of SCA varied by sex and cardiometabolic conditions.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155981"},"PeriodicalIF":10.8,"publicationDate":"2024-07-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141759755","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cardiomyocyte LGR6 alleviates ferroptosis in diabetic cardiomyopathy via regulating mitochondrial biogenesis","authors":"Mengmeng Zhao ,&nbsp;Zican Shen ,&nbsp;Zihui Zheng ,&nbsp;Yao Xu ,&nbsp;Jishou Zhang ,&nbsp;Jianfang Liu ,&nbsp;Shanshan Peng ,&nbsp;Jun Wan ,&nbsp;Juan-Juan Qin ,&nbsp;Menglong Wang","doi":"10.1016/j.metabol.2024.155979","DOIUrl":"10.1016/j.metabol.2024.155979","url":null,"abstract":"<div><h3>Aims</h3><p>The majority of people with diabetes are susceptible to cardiac dysfunction and heart failure, and conventional drug therapy cannot correct the progression of diabetic cardiomyopathy. We assessed the potential role and therapeutic value of LGR6 (G protein-coupled receptor containing leucine-rich repeats 6) in diabetic cardiomyopathy.</p></div><div><h3>Methods and results</h3><p>Type 2 diabetes models were established using high-fat diet/streptozotocin-induced diabetes in mice. LGR6 knockout mice were generated. Recombinant adeno-associated virus serotype 9 carrying LGR6 under the cardiac troponin T promoter was injected into diabetic mice. Cardiomyocytes incubated with high glucose (HG) were used to imitate diabetic cardiomyopathy in vitro. The molecular mechanism was explored through RNA sequencing and a chromatin immunoprecipitation assay. We found that LGR6 expression was upregulated in diabetic hearts and HL1 cardiomyocytes treated with HG. The LGR6 knockout aggravated, but cardiomyocyte-specific LGR6 overexpression ameliorated, cardiac dysfunction and remodeling in diabetic mice. Mechanistically, in vivo and in vitro experiments revealed that LGR6 deletion aggravated, whereas LGR6 overexpression alleviated, ferroptosis and disrupted mitochondrial biogenesis by regulating STAT3/Pgc1a signaling. STAT3 inhibition and Pgc1a activation abrogated LGR6 knockout-induced mitochondrial dysfunction and ferroptosis in diabetic mice. In addition, LGR6 activation by recombinant RSPO3 treatment ameliorated cardiac dysfunction, ferroptosis and mitochondrial dysfunction in diabetic mice.</p></div><div><h3>Conclusions</h3><p>We identified a previously undescribed signaling pathway of the LGR6-STAT3-Pgc1a axis that plays a critical role in ferroptosis and mitochondrial disorders during diabetic cardiomyopathy and provides an option for treatment of diabetic hearts.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"159 ","pages":"Article 155979"},"PeriodicalIF":10.8,"publicationDate":"2024-07-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141748578","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estrogen receptor-α signaling in tanycytes lies at the crossroads of fertility and metabolism","authors":"Daniela Fernandois ,&nbsp;Mariam Rusidzé ,&nbsp;Helge Mueller-Fielitz ,&nbsp;Florent Sauve ,&nbsp;Eleonora Deligia ,&nbsp;Mauro S.B. Silva ,&nbsp;Florence Evrard ,&nbsp;Aurelio Franco-García ,&nbsp;Daniele Mazur ,&nbsp;Ines Martinez-Corral ,&nbsp;Nathalie Jouy ,&nbsp;S. Rasika ,&nbsp;Claude-Alain Maurage ,&nbsp;Paolo Giacobini ,&nbsp;Ruben Nogueiras ,&nbsp;Benedicte Dehouck ,&nbsp;Markus Schwaninger ,&nbsp;Francoise Lenfant ,&nbsp;Vincent Prevot","doi":"10.1016/j.metabol.2024.155976","DOIUrl":"10.1016/j.metabol.2024.155976","url":null,"abstract":"<div><h3>Background</h3><p>Estrogen secretion by the ovaries regulates the hypothalamic-pituitary-gonadal axis during the reproductive cycle, influencing gonadotropin-releasing hormone (GnRH) and luteinizing hormone (LH) secretion, and also plays a role in regulating metabolism. Here, we establish that hypothalamic tanycytes—specialized glia lining the floor and walls of the third ventricle—integrate estrogenic feedback signals from the gonads and couple reproduction with metabolism by relaying this information to orexigenic neuropeptide Y (NPY) neurons.</p></div><div><h3>Methods</h3><p>Using mouse models, including mice floxed for <em>Esr1</em> (encoding estrogen receptor alpha, ERα) and those with Cre-dependent expression of designer receptors exclusively activated by designer drugs (DREADDs), along with viral-mediated, pharmacological and indirect calorimetric approaches, we evaluated the role of tanycytes and tanycytic estrogen signaling in pulsatile LH secretion, cFos expression in NPY neurons, estrous cyclicity, body-weight changes and metabolic parameters in adult females.</p></div><div><h3>Results</h3><p>In ovariectomized mice, chemogenetic activation of tanycytes significantly reduced LH pulsatile release, mimicking the effects of direct NPY neuron activation. In intact mice, tanycytes were crucial for the estrogen-mediated control of GnRH/LH release, with tanycytic ERα activation suppressing fasting-induced NPY neuron activation. Selective knockout of <em>Esr1</em> in tanycytes altered estrous cyclicity and fertility in female mice and affected estrogen's ability to inhibit refeeding in fasting mice. The absence of ERα signaling in tanycytes increased <em>Npy</em> transcripts and body weight in intact mice and prevented the estrogen-mediated decrease in food intake as well as increase in energy expenditure and fatty acid oxidation in ovariectomized mice.</p></div><div><h3>Conclusions</h3><p>Our findings underscore the pivotal role of tanycytes in the neuroendocrine coupling of reproduction and metabolism, with potential implications for its age-related deregulation after menopause.</p></div><div><h3>Significance statement</h3><p>Our investigation reveals that tanycytes, specialized glial cells in the brain, are key interpreters of estrogen signals for orexigenic NPY neurons in the hypothalamus. Disrupting tanycytic estrogen receptors not only alters fertility in female mice but also impairs the ability of estrogens to suppress appetite. This work thus sheds light on the critical role played by tanycytes in bridging the hormonal regulation of cyclic reproductive function and appetite/feeding behavior. This understanding may have potential implications for age-related metabolic deregulation after menopause.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155976"},"PeriodicalIF":10.8,"publicationDate":"2024-07-15","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524002038/pdfft?md5=d2545dea26684f2163b988792a4ac788&pid=1-s2.0-S0026049524002038-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141633937","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Intricate interplay between cell metabolism and necroptosis regulation in metabolic dysfunction-associated steatotic liver disease: A narrative review","authors":"Marta Bento Afonso ,&nbsp;Jan Caira David ,&nbsp;Mariana Isabel Alves ,&nbsp;André Anastácio Santos ,&nbsp;Gonçalo Campino ,&nbsp;Vlad Ratziu ,&nbsp;Jérémie Gautheron ,&nbsp;Cecília Maria Pereira Rodrigues","doi":"10.1016/j.metabol.2024.155975","DOIUrl":"10.1016/j.metabol.2024.155975","url":null,"abstract":"<div><p>Metabolic dysfunction-associated steatotic liver disease (MASLD), formerly known as non-alcoholic fatty liver disease (NAFLD), encompasses a progressive spectrum of liver conditions, ranging from steatosis to metabolic dysfunction-associated steatohepatitis, characterised by hepatocellular death and inflammation, potentially progressing to cirrhosis and/or liver cancer. In both experimental and human MASLD, necroptosis-a regulated immunogenic necrotic cell death pathway-is triggered, yet its exact role in disease pathogenesis remains unclear. Noteworthy, necroptosis-related signalling pathways are emerging as key players in metabolic reprogramming, including lipid and mitochondrial metabolism. Additionally, metabolic dysregulation is a well-established contributor to MASLD development and progression. This review explores the intricate interplay between cell metabolism and necroptosis regulation and its impact on MASLD pathogenesis. Understanding these cellular events may offer new insights into the complexity of MASLD pathophysiology, potentially uncovering therapeutic opportunities and unforeseen metabolic consequences of targeting necroptosis.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155975"},"PeriodicalIF":10.8,"publicationDate":"2024-07-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524002026/pdfft?md5=e60fb78b8210753a78a7e626301318b8&pid=1-s2.0-S0026049524002026-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141616848","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Metabolic reprogramming in septic acute kidney injury: pathogenesis and therapeutic implications","authors":"Caihong Liu ,&nbsp;Wei Wei ,&nbsp;Yongxiu Huang,&nbsp;Ping Fu,&nbsp;Ling Zhang,&nbsp;Yuliang Zhao","doi":"10.1016/j.metabol.2024.155974","DOIUrl":"10.1016/j.metabol.2024.155974","url":null,"abstract":"<div><p>Acute kidney injury (AKI) is a frequent and severe complication of sepsis and is characterized by significant mortality and morbidity. However, the pathogenesis of septic acute kidney injury (S-AKI) remains elusive. Metabolic reprogramming, which was originally referred to as the Warburg effect in cancer, is strongly related to S-AKI. At the onset of sepsis, both inflammatory cells and renal parenchymal cells, such as macrophages, neutrophils and renal tubular epithelial cells, undergo metabolic shifts toward aerobic glycolysis to amplify proinflammatory responses and fortify cellular resilience to septic stimuli. As the disease progresses, these cells revert to oxidative phosphorylation, thus promoting anti-inflammatory reactions and enhancing functional restoration. Alterations in mitochondrial dynamics and metabolic reprogramming are central to the energetic changes that occur during S-AKI. In this review, we summarize the current understanding of the pathogenesis of metabolic reprogramming in S-AKI, with a focus on each cell type involved. By identifying relevant key regulatory factors, we also explored potential metabolic reprogramming-related therapeutic targets for the management of S-AKI.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155974"},"PeriodicalIF":10.8,"publicationDate":"2024-07-10","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141600579","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Copper impairs the intestinal barrier integrity in Wilson disease","authors":"Adriana Fontes ,&nbsp;Hannah Pierson ,&nbsp;Joanna B. Bierła ,&nbsp;Carola Eberhagen ,&nbsp;Jennifer Kinschel ,&nbsp;Banu Akdogan ,&nbsp;Tamara Rieder ,&nbsp;Judith Sailer ,&nbsp;Quirin Reinold ,&nbsp;Joanna Cielecka-Kuszyk ,&nbsp;Sylwia Szymańska ,&nbsp;Frauke Neff ,&nbsp;Katja Steiger ,&nbsp;Olga Seelbach ,&nbsp;Andree Zibert ,&nbsp;Hartmut H. Schmidt ,&nbsp;Stefanie M. Hauck ,&nbsp;Christine von Toerne ,&nbsp;Bernhard Michalke ,&nbsp;Jeremy D. Semrau ,&nbsp;Hans Zischka","doi":"10.1016/j.metabol.2024.155973","DOIUrl":"10.1016/j.metabol.2024.155973","url":null,"abstract":"<div><p>In Wilson disease (WD), liver copper (Cu) excess, caused by mutations in the ATPase Cu transporting beta (ATP7B), has been extensively studied. In contrast, in the gastrointestinal tract, responsible for dietary Cu uptake, ATP7B malfunction is poorly explored. We therefore investigated gut biopsies from WD patients and compared intestines from two rodent WD models and from human <em>ATP7B</em> knock-out intestinal cells to their respective wild-type controls.</p><p>We observed gastrointestinal (GI) inflammation in patients, rats and mice lacking ATP7B. Mitochondrial alterations and increased intestinal leakage were observed in WD rats, <em>Atp7b</em>^−/− mice and human <em>ATP7B</em> KO Caco-2 cells. Proteome analyses of intestinal WD homogenates revealed profound alterations of energy and lipid metabolism. The intestinal damage in WD animals and human <em>ATP7B</em> KO cells did not correlate with absolute Cu elevations, but likely reflects intracellular Cu mislocalization. Importantly, Cu depletion by the high-affinity Cu chelator methanobactin (MB) restored enterocyte mitochondria, epithelial integrity, and resolved gut inflammation in WD rats and human WD enterocytes, plausibly via autophagy-related mechanisms.</p><p>Thus, we report here before largely unrecognized intestinal damage in WD, occurring early on and comprising metabolic and structural tissue damage, mitochondrial dysfunction, and compromised intestinal barrier integrity and inflammation, that can be resolved by high-affinity Cu chelation treatment.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155973"},"PeriodicalIF":10.8,"publicationDate":"2024-07-08","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.sciencedirect.com/science/article/pii/S0026049524002002/pdfft?md5=a81b9cd717ecc0cefa2ed60915062c03&pid=1-s2.0-S0026049524002002-main.pdf","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141580236","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"New insights into the function of the NLRP3 inflammasome in sarcopenia: mechanism and therapeutic strategies","authors":"Yunyi Zou ,&nbsp;Xiangbin Tang ,&nbsp;Siyuan Yang,&nbsp;Zhanglin Chen,&nbsp;Bin Liu,&nbsp;Zuoqiong Zhou,&nbsp;Xiyang Peng,&nbsp;Changfa Tang","doi":"10.1016/j.metabol.2024.155972","DOIUrl":"10.1016/j.metabol.2024.155972","url":null,"abstract":"<div><p>Sarcopenia is one of the most common skeletal muscle disorders and is characterized by infirmity and disability. While extensive research has focused on elucidating the mechanisms underlying the progression of sarcopenia, further comprehensive insights into its pathogenesis are necessary to identify new preventive and therapeutic approaches. The involvement of inflammasomes in sarcopenia is widely recognized, with particular emphasis on the NLRP3 (NLR family pyrin domain containing 3) inflammasome. In this review, we aim to elucidate the underlying mechanisms of the NLRP3 inflammasome and its relevance in sarcopenia of various etiologies. Furthermore, we highlight interventions targeting the NLRP3 inflammasome in the context of sarcopenia and discuss the current limitations of our knowledge in this area.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155972"},"PeriodicalIF":10.8,"publicationDate":"2024-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141555220","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Estradiol contributes to sex differences in resilience to sepsis-induced metabolic dysregulation and dysfunction in the heart via GPER-1-mediated PPARδ/NLRP3 signaling.","authors":"Joseph Adu-Amankwaah, Adebayo Oluwafemi Adekunle, Ziqing Tang, Aisha Bushi, Rubin Tan, Lu Fu, Zheng Gong, Ziyu Ma, Richard Mprah, Marie Louise Ndzie Noah, Prosperl Ivette Wowui, Jeremiah Ong'achwa Machuki, Xiuhua Pan, Tao Li, Hong Sun","doi":"10.1016/j.metabol.2024.155934","DOIUrl":"10.1016/j.metabol.2024.155934","url":null,"abstract":"<p><strong>Background and aim: </strong>Clinically, septic males tend to have higher mortality rates, but it is unclear if this is due to sex differences in cardiac dysfunction, possibly influenced by hormonal variations. Cardiac dysfunction significantly contributes to sepsis-related mortality, primarily influenced by metabolic imbalances. Peroxisome proliferator-activated receptor delta (PPARδ) is a key player in cardiac metabolism and its activation has been demonstrated to favor sepsis outcomes. While estradiol (E2) is abundant and beneficial in females, its impact on PPARδ-mediated metabolism in the heart with regards to sex during sepsis remains unknown.</p><p><strong>Methods and results: </strong>Here, we unveil that while sepsis diminishes PPARδ nuclear translocation and induces metabolic dysregulation, oxidative stress, apoptosis and dysfunction in the heart thereby enhancing mortality, these effects are notably more pronounced in males than females. Mechanistic experiments employing ovariectomized(OVX) mice, E2 administration, and G protein-coupled estrogen receptor 1(GPER-1) knockout (KO) mice revealed that under lipopolysaccharide (LPS)-induced sepsis, E2 acting via GPER-1 enhances cardiac electrical activity and function, promotes PPARδ nuclear translocation, and subsequently ameliorates cardiac metabolism while mitigating oxidative stress and apoptosis in females. Furthermore, PPARδ specific activation using GW501516 in female GPER-1^-/- mice reduced oxidative stress, ultimately decreasing NLRP3 expression in the heart. Remarkably, targeted GPER-1 activation using G1 in males mirrors these benefits, improving cardiac electrical activity and function, and ultimately enhancing survival rates during LPS challenge. By employing NLRP3 KO mice, we demonstrated that the targeted GPER-1 activation mitigated injury, enhanced metabolism, and reduced apoptosis in the heart of male mice via the downregulation of NLRP3.</p><p><strong>Conclusion: </strong>Our findings collectively illuminate the sex-specific cardiac mechanisms influencing sepsis mortality, offering insights into physiological and pathological dimensions. From a pharmacological standpoint, this study introduces specific GPER-1 activation as a promising therapeutic intervention for males under septic conditions. These discoveries advance our understanding of the sex differences in sepsis-induced cardiac dysfunction and also present a novel avenue for targeted interventions with potential translational impact.</p>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":" ","pages":"155934"},"PeriodicalIF":10.8,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140958503","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Fasting-induced miR-7a-5p in AgRP neurons regulates food intake","authors":"Mingyang Yuan ,&nbsp;Zhiwen Cao ,&nbsp;Qian Li ,&nbsp;Ruixin Liu ,&nbsp;Jiqiu Wang ,&nbsp;Wenzhi Xue ,&nbsp;Qianqian Lyu","doi":"10.1016/j.metabol.2024.155959","DOIUrl":"10.1016/j.metabol.2024.155959","url":null,"abstract":"<div><h3>Objective</h3><p>The molecular control of feeding after fasting is essential for maintaining energy homeostasis, while overfeeding usually leads to obesity. Identifying non-coding microRNAs (miRNAs) that control food intake could reveal new oligonucleotide-based therapeutic targets for treating obesity and its associated diseases. This study aims to identify a miRNA modulating food intake and its mechanism in neuronal regulation of food intake and energy homeostasis.</p></div><div><h3>Methods</h3><p>A comprehensive genome-wide miRNA screening in the arcuate nucleus of the hypothalamus (ARC) of fasted mice and <em>ad libitum</em> mice was performed. Through stereotactic virus injections, intracerebroventricular injections, and miRNA sponge technology, miR-7a-5p was inhibited specifically in AgRP neurons and the central nervous system, and metabolic phenotypes were monitored. Quantitative real-time PCR, Western blotting, immunofluorescence, whole-cell patch-clamp recording, and luciferase reporter assay were used to investigate the mechanisms underlying miR-7a-5p’s regulation of food intake.</p></div><div><h3>Results</h3><p>We found a significant increase in miR-7a-5p levels after fasting. miR-7a-5p was highly expressed in the ARC, and inhibition of miR-7a-5p specifically in AgRP neurons reduced food intake and body weight gain. miR-7a-5p inhibited S6K1 gene expression by binding to its 3’-UTR. Furthermore, the knockdown of ribosomal S6 kinase 1 (S6K1) in AgRP neurons can partially reverse the effects caused by miR-7a-5p inhibition. Importantly, intracerebroventricular administration of the miR-7a-5p inhibitor could also reduce food intake and body weight gain.</p></div><div><h3>Conclusion</h3><p>Our findings suggest that miR-7a-5p responds to energy deficit and regulates food intake by fine-tuning mTOR1/S6K1 signaling in the AgRP neurons, which could be a promising oligonucleotide-based therapeutic target for treating obesity and its associated diseases.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155959"},"PeriodicalIF":10.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Disparities in metabolic dysfunction-associated steatotic liver disease and cardiometabolic conditions in low and lower middle-income countries: a systematic analysis from the global burden of disease study 2019","authors":"Pojsakorn Danpanichkul ,&nbsp;Kanokphong Suparan ,&nbsp;Priyata Dutta ,&nbsp;Chuthathip Kaeosri ,&nbsp;Banthoon Sukphutanan ,&nbsp;Yanfang Pang ,&nbsp;Narathorn Kulthamrongsri ,&nbsp;Methasit Jaisa-aad ,&nbsp;Cheng Han Ng ,&nbsp;Margaret Teng ,&nbsp;Masahito Nakano ,&nbsp;Asahiro Morishita ,&nbsp;Naim Alkhouri ,&nbsp;Ju Dong Yang ,&nbsp;Vincent L. Chen ,&nbsp;Donghee Kim ,&nbsp;Michael B. Fallon ,&nbsp;Luis Antonio Diaz ,&nbsp;Juan Pablo Arab ,&nbsp;Christos S. Mantzoros ,&nbsp;Karn Wijarnpreecha","doi":"10.1016/j.metabol.2024.155958","DOIUrl":"10.1016/j.metabol.2024.155958","url":null,"abstract":"<div><h3>Objective</h3><p>Metabolic dysfunction-associated steatotic liver disease (MASLD) and cardiometabolic conditions affect populations across economic strata. Nevertheless, there are limited epidemiological studies addressing these diseases in low (LICs) and lower-middle-income countries (lower MICs). Therefore, an analysis of the trend of MASLD and cardiometabolic conditions in these countries is necessary.</p></div><div><h3>Methods</h3><p>From 2000 to 2019, jointpoint regression analysis was employed to calculate the prevalence, mortality, and disability-adjusted life years (DALYs) for cardiometabolic conditions including MASLD, type 2 diabetes mellitus (T2DM), dyslipidemia (DLP), hypertension (HTN), obesity, peripheral artery disease (PAD), atrial fibrillation and flutter (AF/AFL), ischemic heart disease (IHD), stroke, and chronic kidney disease from HTN and T2DM, in LICs and lower MICs (according to the World Bank Classification 2019) using the Global Burden of Disease 2019 data.</p></div><div><h3>Results</h3><p>Among the eleven cardiometabolic conditions, MASLD (533.65 million), T2DM (162.96 million), and IHD (76.81 million) had the highest prevalence in LICs and Lower MICs in 2019. MASLD represented the largest proportion of global prevalence in these countries (43 %). From 2000 to 2019, mortality in LICs and lower MICs increased in all cardiometabolic conditions, with obesity-related mortality having the highest increase (+134 %). During this timeframe, there were increased age-standardized death rates (ASDR) from obesity, PAD, and AF/AFL. From all conditions, the DALYs-to-prevalence ratio was higher in LICs and lower MICs than the global average.</p></div><div><h3>Conclusion</h3><p>The burden of MASLD and cardiometabolic conditions is increasing worldwide, with LICs and lower MICs experiencing higher (DALYs) disability per prevalence. As these conditions are preventable, counteracting these trends requires not only the modification of ongoing actions but also the strategizing of immediate interventions.</p></div>","PeriodicalId":18694,"journal":{"name":"Metabolism: clinical and experimental","volume":"158 ","pages":"Article 155958"},"PeriodicalIF":10.8,"publicationDate":"2024-06-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"141469515","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}