[{"data":1,"prerenderedAt":-1},["ShallowReactive",2],{"doc-seo-455713-105":3,"detail-sidebar-cat-0-en-105":80,"doc-detail-455713-en":130},{"code":4,"msg":5,"data":6},0,"ok",{"site_id":7,"language":8,"slug":9,"title":10,"keywords":11,"description":12,"schema_data":13,"social_meta":73,"head_meta":75,"extra_data":77,"updated_unix":79},105,"en","deletion-of-mmp12-improves-energy-metabolism-and-brown-adipose-tissue-function-in-mice-prone-to-cardiometabolic-disease","Deletion of MMP12 improves energy metabolism and brown adipose tissue function in mice prone to cardiometabolic disease","","Matrix metalloproteinase-12 (MMP12) is a proinflammatory macrophage-secreted protein involved in immunomodulatory processes that influence neutrophil infiltration, cytokine release, macrophage recruitment, and proliferation. Genetic deletion of MMP12 previously reduced obesity-driven low-grade inflammation, white adipose tissue dysfunction, and atherosclerosis. Here, Ldlr/Mmp12 double knockout mice on a high-fat sucrose- and cholesterol-enriched diet showed higher energy expenditure and impaired brown adipose tissue (BAT) lipid storage, alongside enhanced mitochondrial, glucose, and fatty-acid oxidation pathways with reduced inflammation and macrophage infiltration. Acute cold exposure further increased thermogenic gene expression while lowering circulating lipid concentrations.",{"@graph":14,"@context":72},[15,34,55],{"@type":16,"itemListElement":17},"BreadcrumbList",[18,23,27,31],{"item":19,"name":20,"@type":21,"position":22},"https://docshare.wps.com","Home","ListItem",1,{"item":24,"name":25,"@type":21,"position":26},"https://docshare.wps.com/document/","Document",2,{"item":28,"name":29,"@type":21,"position":30},"https://docshare.wps.com/document/research-report/","Research & Report",3,{"item":32,"name":10,"@type":21,"position":33},"https://docshare.wps.com/document/deletion-of-mmp12-improves-energy-metabolism-and-brown-adipose-tissue-function-in-mice-prone-to-cardiometabolic-disease/455713/",4,{"url":32,"name":10,"@type":35,"image":36,"author":41,"headline":10,"publisher":44,"fileFormat":47,"inLanguage":8,"description":12,"dateModified":48,"datePublished":49,"encodingFormat":47,"isAccessibleForFree":50,"interactionStatistic":51},"DigitalDocument",{"url":37,"@type":38,"width":39,"height":40},"https://docshare.wps.com/thumbnails/deletion-of-mmp12-improves-energy-metabolism-and-brown-adipose-tissue-function-in-mice-prone-to-cardiometabolic-disease/455713.png","ImageObject",300,407,{"name":42,"@type":43},"Genevieve","Person",{"url":19,"name":45,"@type":46},"DocShare","Organization","application/pdf","2026-10-03","2026-09-30",true,{"@type":52,"interactionType":53,"userInteractionCount":30},"InteractionCounter",{"@type":54},"ViewAction",{"@type":56,"mainEntity":57},"FAQPage",[58,64,68],{"name":59,"@type":60,"acceptedAnswer":61},"What hypothesis guided the study of MMP12 deletion?","Question",{"text":62,"@type":63},"Based on prior findings that MMP12 loss improves multiple cardiometabolic phenotypes, the study hypothesized that deleting MMP-12 would also improve whole-body energy metabolism and/or brown adipose tissue (BAT) function in a cardiometabolic mouse model.","Answer",{"name":65,"@type":60,"acceptedAnswer":66},"How were the effects of MMP12 deletion tested in mice?",{"text":67,"@type":63},"Ldlr/Mmp12 double knockout mice were fed a high-fat, sucrose- and cholesterol-enriched diet and compared under thermometabolic conditions, including housing at 22◦C and an acute cold exposure challenge.",{"name":69,"@type":60,"acceptedAnswer":70},"What molecular and pathway changes were observed in BAT after MMP12 deletion?",{"text":71,"@type":63},"Untargeted proteomic analyses showed upregulation of proteins and pathways linked to mitochondrial function, glucose metabolism, and fatty acid oxidation, while pathways associated with inflammation were reduced; mitochondria also showed reduced compactness and sphericity.","https://schema.org",{"og:url":32,"og:type":74,"og:title":10,"og:site_name":45,"og:description":12},"article",{"robots":76,"canonical":32},"index,follow",{"doc_id":78,"site_id":7},455713,1790985794,{"code":4,"msg":81,"data":82},"success",[83,87,91,95,100,105,110,114,119,122,126],{"id":22,"doc_module":4,"doc_module_name":25,"category_name":84,"show_sort_weight":85,"slug":86},"Story & Novel",90,"story-novel",{"id":26,"doc_module":4,"doc_module_name":25,"category_name":88,"show_sort_weight":89,"slug":90},"Literature",80,"literature",{"id":33,"doc_module":4,"doc_module_name":25,"category_name":92,"show_sort_weight":93,"slug":94},"Exam",70,"exam",{"id":96,"doc_module":4,"doc_module_name":25,"category_name":97,"show_sort_weight":98,"slug":99},5,"Comic",60,"comic",{"id":101,"doc_module":4,"doc_module_name":25,"category_name":102,"show_sort_weight":103,"slug":104},6,"Technology",50,"technology",{"id":106,"doc_module":4,"doc_module_name":25,"category_name":107,"show_sort_weight":108,"slug":109},7,"Healthcare",40,"healthcare",{"id":111,"doc_module":4,"doc_module_name":25,"category_name":29,"show_sort_weight":112,"slug":113},8,30,"research-report",{"id":115,"doc_module":4,"doc_module_name":25,"category_name":116,"show_sort_weight":117,"slug":118},9,"Religion & Spirituality",20,"religion-spirituality",{"id":117,"doc_module":4,"doc_module_name":25,"category_name":120,"show_sort_weight":117,"slug":121},"World Cup","world-cup",{"id":123,"doc_module":4,"doc_module_name":25,"category_name":124,"show_sort_weight":123,"slug":125},10,"Lifestyle","lifestyle",{"id":127,"doc_module":4,"doc_module_name":25,"category_name":128,"show_sort_weight":96,"slug":129},19,"General","general",{"code":4,"msg":81,"data":131},{"doc_id":78,"user_id":132,"nickname":42,"user_avatar":133,"doc_module":4,"category_id":111,"category_name":29,"doc_title":10,"doc_description":12,"doc_content":134,"file_id":135,"file_url":136,"file_type":137,"file_size":138,"view_count":30,"is_deleted":4,"is_public":22,"is_downloadable":22,"audit_status":22,"page_count":139,"language":140,"language_code":8,"site_id":7,"html_lang":8,"table_of_contents":141,"faqs":142,"seo_title":143,"seo_description":12,"update_tm":144,"read_time":108},1374391974585,"https://ap-avatar.wpscdn.com/davatar_276721f389ce27ea32af1340a28f341c","RESEARCH ARTICLE  \nDeletion of MMP12 improves energy metabolism and brown adipose tissue function in mice prone to cardiometabolic disease  \nMelina Amor1 , Malena Diaz1 , Alexander Fuerlinger2 , Monika Svecla3 , Valentina Bianco1 , Laszlo Schooltink1, Anja Dobrijevi´c1, Birgit Schwarz1, Alena Akhmetshina1, Nemanja Vuji´c1 , Melanie Korbelius1 , Martin Hirtl1 , Martin Buerger1, Anita Pirchheim1, Silvia Rainer1, Silvia Schauer4, Giangiacomo Beretta5, Walter Goessler6, Dagmar Kolb7,8,9, Gerald Hoefler4 , Hubert Hackl10 , Corina Madreiter-Sokolowski1,9, Mahmoud Abdellatif2,9 , Giuseppe Danilo Norata3 , and  \nDagmar Kratky1,9,*  \n1Molecular Biology and Biochemistry, Gottfried Schatz Research Center, and 2Department of Cardiology, Medical University of Graz, Graz, Austria; 3Department of Pharmacological and Biomolecular Sciences, University of Milan, Milan, Italy; 4Diagnostics and Research Institute of Pathology, Medical University of Graz, Graz, Austria; 5Department of Environmental Science and Policy, Universit`a degli Studi di Milano, Milan, Italy; 6Institute of Analytical Chemistry, University of Graz, Graz, Austria; 7Cell Biology, Histology and Embryology, Gottfried Schatz Research Center, and 8Core Facility Ultrastructural Analysis, Medical University of Graz, Graz, Austria; 9BioTechMed-Graz, Graz, Austria; and 10Institute of Bioinformatics, Medical University of Innsbruck, Innsbruck, Austria  \nAbstract Matrix metalloproteinase-12 (MMP12) is aproinflammatory macrophage-secreted protein with immunomodulatory functions that affects neutrophil infiltration, cytokine release, macrophage recruitment, and proliferation. We have previously demonstrated that the genetic deletion of MMP12 in a cardiometabolic mouse model ameliorates obesityinduced low-grade inflammation, white adipose tissue dysfunction, and atherosclerosis. Based on the various beneficial metabolic effects of MMP-12 deletion, we hypothesized that loss of MMP-12 also positively affects whole-body energy metabolism and/or brown adipose tissue (BAT) function in a cardiometabolic mouse model. To investigate the effects of MMP12 deletion on whole-body energy metabolism and/or BAT function, we used lowdensity lipoprotein receptor (Ldlr)/Mmp12 double knockout (DKO) fed a high-fat, sucrose- and  \ncholesterol-enriched diet. DKO mice housed at 22◦ C showed increased energy expenditure and decreased BAT size and triglyceride (TG) content. Untargeted proteomic analyses revealed the upregulation of proteins and pathways related to mitochondrial function, glucose metabolism, and fatty acid oxidation in the BAT of DKO mice, whereas the abundance of proteins and pathways associated with inflammation was reduced. In addition, DKO mice exhibited reduced macrophage infiltration in BAT, with the infiltrating macrophages showing lower  \nexpression of lipid-associated marker genes. Loss of MMP12 was associated with reduced compactness and sphericity of the mitochondria in the BAT. Following an acute cold exposure, DKO mice had decreased circulating lipid concentrations, especially very low-density lipoprotein-TG and LDLcholesterol, and increased expression of thermogenic genes.  We conclude that MMP12 may play a  \n*For correspondence: Dagmar Kratky, dagmar.kratky@medunigraz.at.  \nCurrent address for Monika Svecla: Department of Neurosurgery, Charit´e − Universitätsmedizin Berlin, Berlin, Germany.  \nCurrent address for Valentina Bianco: Bio-ReCell d.o.o, Ljubljana, Slovenia.  \nCurrent address for Anja Dobrijevi´c: Institute for Vascular Biology, Center for Physiology and Pharmacology, Medical University of Vienna, Vienna, Austria.  \n J. Lipid Res. (2026) 67(1) 100951 1  \ndetrimental role in whole-body energy homeostasis and thermogenesis, as it triggers macrophage infiltration, inflammation, and mitochondrial dysfunction in BAT.  \nSupplementary key words from JLR list Adipose tissue • brown • Extracellular matrix • Inflammation • Mitochondria • Proteomics  \nBrown adipose tissue (BAT) is a t","cbCaipXtEBqWJAER","https://ap.wps.com/l/cbCaipXtEBqWJAER","pdf",11605393,16,"English","# Abstract\n## Background and hypothesis\n## Experimental model and diet\n## Effects on energy expenditure and BAT composition\n## Proteomic pathway changes\n## Macrophage infiltration and mitochondrial morphology\n## Cold exposure outcomes and conclusion","[{\"question\":\"What hypothesis guided the study of MMP12 deletion?\",\"answer\":\"Based on prior findings that MMP12 loss improves multiple cardiometabolic phenotypes, the study hypothesized that deleting MMP-12 would also improve whole-body energy metabolism and/or brown adipose tissue (BAT) function in a cardiometabolic mouse model.\"},{\"question\":\"How were the effects of MMP12 deletion tested in mice?\",\"answer\":\"Ldlr/Mmp12 double knockout mice were fed a high-fat, sucrose- and cholesterol-enriched diet and compared under thermometabolic conditions, including housing at 22◦C and an acute cold exposure challenge.\"},{\"question\":\"What molecular and pathway changes were observed in BAT after MMP12 deletion?\",\"answer\":\"Untargeted proteomic analyses showed upregulation of proteins and pathways linked to mitochondrial function, glucose metabolism, and fatty acid oxidation, while pathways associated with inflammation were reduced; mitochondria also showed reduced compactness and sphericity.\"}]","Deletion of MMP12 improves energy metabolism and brown adipose tissue function in mice prone to cardiometabolic disease | PDF",1790743945]