{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,22]],"date-time":"2026-09-22T14:34:04Z","timestamp":1790087644348,"version":"4.0.1"},"reference-count":53,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T00:00:00Z","timestamp":1679443200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100004329","name":"Javna Agencija za Raziskovalno Dejavnost RS","doi-asserted-by":"publisher","award":["P3-0043, J7-3153, BI-HR\/20-21-041"],"award-info":[{"award-number":["P3-0043, J7-3153, BI-HR\/20-21-041"]}],"id":[{"id":"10.13039\/501100004329","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100004488","name":"Hrvatska Zaklada za Znanost","doi-asserted-by":"publisher","award":["HrZZ-UIP-2017-05-7260, BI-HR\/20-21-041"],"award-info":[{"award-number":["HrZZ-UIP-2017-05-7260, BI-HR\/20-21-041"]}],"id":[{"id":"10.13039\/501100004488","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Endocrinol."],"abstract":"<jats:p>Expression of patatin-like phospholipase domain containing protein 7 (PNPLA7), also known as neuropathy target esterase-related esterase (NRE), a lysophospholipase, increases with fasting and decreases with feeding in mouse skeletal muscle, indicating it is regulated by insulin, counterregulatory hormones, such as glucocorticoids and catecholamines, and\/or nutrients. In cultured mouse adipocytes insulin reduces <jats:italic>Pnpla7<\/jats:italic> expression, underscoring the possibility that insulin regulates PNPLA7 in skeletal muscle. The first aim of this study was to establish whether PNPLA7 is functionally expressed in cultured human skeletal muscle cells. The second aim was to determine whether PNPLA7 is regulated by insulin, glucocorticoids, cAMP\/protein kinase A pathway, and\/or glucose. Cultured human skeletal muscle cells expressed <jats:italic>PNPLA7<\/jats:italic> mRNA and protein. Gene silencing of PNPLA7 in myoblasts reduced the phosphorylation of 70 kDa ribosomal protein S6 kinase and ribosomal protein S6 as well as the abundance of \u03b11-subunit of Na<jats:sup>+<\/jats:sup>,K<jats:sup>+<\/jats:sup>-ATPase and acetyl-CoA carboxylase, indirectly suggesting that PNPLA7 is functionally important. In myotubes, insulin suppressed <jats:italic>PNPLA7<\/jats:italic> mRNA at 1 g\/L glucose, but not at low (0.5 g\/L) or high (4.5 g\/L) concentrations. Treatment with synthetic glucocorticoid dexamethasone and activator of adenylyl cyclase forskolin had no effect on PNPLA7 regardless of glucose concentration, while dibutyryl-cAMP, a cell-permeable cAMP analogue, suppressed <jats:italic>PNPLA7<\/jats:italic> mRNA at 4.5 g\/L glucose. The abundance of PNPLA7 protein correlated inversely with the glucose concentrations. Collectively, our results highlight that PNPLA7 in human myotubes is regulated by metabolic signals, implicating a role for PNPLA7 in skeletal muscle energy metabolism.<\/jats:p>","DOI":"10.3389\/fendo.2023.1139303","type":"journal-article","created":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T05:48:00Z","timestamp":1679464080000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Insulin, dibutyryl-cAMP, and glucose modulate expression of patatin-like domain containing protein 7 in cultured human myotubes"],"prefix":"10.3389","volume":"14","author":[{"given":"Katarina","family":"Mi\u0161","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ana-Marija","family":"Luli\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toma\u017e","family":"Mar\u0161","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sergej","family":"Pirkmajer","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Maja","family":"Katalini\u0107","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2023,3,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R800082-JLR200","article-title":"Mammalian patatin domain containing proteins: A family with diverse lipolytic activities involved in multiple biological functions","author":"Kienesberger","year":"2009","journal-title":"J Lipid Res"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M600185-JLR200","article-title":"Characterization of the human patatin-like phospholipase family","volume":"47","author":"Wilson","year":"2006","journal-title":"J Lipid Res"},{"key":"B3","doi-asserted-by":"publisher","first-page":"1457","DOI":"10.3390\/biom10101457","article-title":"Updating phospholipase A(2) biology","volume":"10","author":"Murakami","year":"2020","journal-title":"Biomolecules"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1021\/bi027156r","article-title":"The crystal structure, mutagenesis, and activity studies reveal that patatin is a lipid acyl hydrolase with a ser-asp catalytic dyad","volume":"42","author":"Rydel","year":"2003","journal-title":"Biochemistry"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0108245","article-title":"Crystal structure of patatin-17 in complex with aged and non-aged organophosphorus compounds","volume":"9","author":"Wijeyesakere","year":"2014","journal-title":"PloS One"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.R058701","article-title":"Calcium-independent phospholipases A2 and their roles in biological processes and diseases","volume":"56","author":"Ramanadham","year":"2015","journal-title":"J Lipid Res"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2012.10.024","article-title":"Neuropathy target esterase (NTE): Overview and future","volume":"203","author":"Richardson","year":"2013","journal-title":"Chem Biol Interact"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M709598200","article-title":"Identification of an insulin-regulated lysophospholipase with homology to neuropathy target esterase","volume":"283","author":"Kienesberger","year":"2008","journal-title":"J Biol Chem"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M117.792978","article-title":"The phospholipase PNPLA7 functions as a lysophosphatidylcholine hydrolase and interacts with lipid droplets through its catalytic domain","volume":"292","author":"Heier","year":"2017","journal-title":"J Biol Chem"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.14348\/molcells.2020.2283","article-title":"Interaction of the lysophospholipase PNPLA7 with lipid droplets through the catalytic region","volume":"43","author":"Chang","year":"2020","journal-title":"Mol Cells"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.1016\/j.tiv.2010.01.008","article-title":"An alternative in vitro method for detecting neuropathic compounds based on acetylcholinesterase inhibition and on inhibition and aging of neuropathy target esterase (NTE)","volume":"24","author":"Sogorb","year":"2010","journal-title":"Toxicol In Vitro."},{"key":"B12","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1016\/j.tox.2012.03.012","article-title":"NTE and non-NTE esterases in brain membrane: kinetic characterization with organophosphates","volume":"297","author":"Mangas","year":"2012","journal-title":"Toxicology"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1016\/j.biocel.2009.12.007","article-title":"Neuropathy target esterase: an essential enzyme for neural development and axonal maintenance","volume":"42","author":"Chang","year":"2010","journal-title":"Int J Biochem Cell Biol"},{"key":"B14","doi-asserted-by":"publisher","first-page":"67","DOI":"10.1016\/j.toxlet.2010.03.1120","article-title":"Constructs of human neuropathy target esterase catalytic domain containing mutations related to motor neuron disease have altered enzymatic properties","volume":"196","author":"Hein","year":"2010","journal-title":"Toxicol Lett"},{"key":"B15","doi-asserted-by":"publisher","first-page":"54","DOI":"10.1016\/j.neuroscience.2014.08.031","article-title":"Silencing of PNPLA6, the neuropathy target esterase (NTE) codifying gene, alters neurodifferentiation of human embryonal carcinoma stem cells (NT2)","volume":"281","author":"Pamies","year":"2014","journal-title":"Neuroscience"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.1016\/j.cbi.2016.07.030","article-title":"Roles of NTE protein and encoding gene in development and neurodevelopmental toxicity","volume":"259","author":"Sogorb","year":"2016","journal-title":"Chem Biol Interact"},{"key":"B17","doi-asserted-by":"publisher","first-page":"104520","DOI":"10.1016\/j.nbd.2019.104520","article-title":"ER responses play a key role in Swiss-Cheese\/Neuropathy target esterase-associated neurodegeneration","volume":"130","author":"Sunderhaus","year":"2019","journal-title":"Neurobiol Dis"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0003-9861(03)00264-9","article-title":"Rat NTE-related esterase is a membrane-associated protein, hydrolyzes phenyl valerate, and interacts with diisopropylfluorophosphate through a serine catalytic machinery","volume":"416","author":"Xie","year":"2003","journal-title":"Arch Biochem Biophys"},{"key":"B19","doi-asserted-by":"publisher","first-page":"111940","DOI":"10.1016\/j.celrep.2022.111940","article-title":"Hepatic phosphatidylcholine catabolism driven by PNPLA7 and PNPLA8 supplies endogenous choline to replenish the methionine cycle with methyl groups","volume":"42","author":"Hirabayashi","year":"2023","journal-title":"Cell Rep"},{"key":"B20","doi-asserted-by":"publisher","first-page":"25","DOI":"10.1007\/s11010-007-9550-2","article-title":"Molecular cloning and expression of the c-terminal domain of mouse NTE-related esterase","volume":"306","author":"Chang","year":"2007","journal-title":"Mol Cell Biochem"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1002\/hep.31161","article-title":"The patatin-like phospholipase domain containing protein 7 facilitates VLDL secretion by modulating ApoE stability","volume":"72","author":"Wang","year":"2020","journal-title":"Hepatology"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114857","article-title":"Skeletal muscle metabolism is a major determinant of resting energy expenditure","volume":"86","author":"Zurlo","year":"1990","journal-title":"J Clin Invest"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1997.77.3.731","article-title":"Cellular energy utilization and molecular origin of standard metabolic rate in mammals","volume":"77","author":"Rolfe","year":"1997","journal-title":"Physiol Rev"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-010-1684-1","article-title":"Insulin resistance, lipotoxicity, type 2 diabetes and atherosclerosis: The missing links. the Claude Bernard lecture 2009","volume":"53","author":"DeFronzo","year":"2010","journal-title":"Diabetologia"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.2337\/dc09-S302","article-title":"Skeletal muscle insulin resistance is the primary defect in type 2 diabetes","author":"DeFronzo","year":"2009","journal-title":"Diabetes Care"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1172\/JCI111938","article-title":"Effects of insulin on peripheral and splanchnic glucose metabolism in noninsulin-dependent (type II) diabetes mellitus","volume":"76","author":"DeFronzo","year":"1985","journal-title":"J Clin Invest."},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1177\/03009858211030541","article-title":"Histopathology is required to identify and characterize myopathies in high-throughput phenotype screening of genetically engineered mice","volume":"58","author":"Vogel","year":"2021","journal-title":"Vet Pathol"},{"key":"B28","doi-asserted-by":"crossref","first-page":"13 p","DOI":"10.1016\/B978-0-12-819090-6.00049-0","article-title":"Chapter 49 - the effects of organophosphates in the early stages of human skeletal muscle regeneration","volume-title":"Handbook of toxicology of chemical warfare agents (Third edition)","author":"Mars","year":"2020"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0247377","article-title":"Effect of differentiation, de novo innervation, and electrical pulse stimulation on mRNA and protein expression of Na+,K+-ATPase, FXYD1, and FXYD5 in cultured human skeletal muscle cells","volume":"16","author":"Jan","year":"2021","journal-title":"PloS One"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1139\/apnm-2019-0575","article-title":"Innervation and electrical pulse stimulation - in vitro effects on human skeletal muscle cells","volume":"46","author":"Mars","year":"2020","journal-title":"Appl Physiol Nutr Metab"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2020.566584","article-title":"Ouabain suppresses IL-6\/STAT3 signaling and promotes cytokine secretion in cultured skeletal muscle cells","volume":"11","author":"Pirkmajer","year":"2020","journal-title":"Front Physiol"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00311.2017","article-title":"Nucleosides block AICAR-stimulated activation of AMPK in skeletal muscle and cancer cells","volume":"315","author":"Dolinar","year":"2018","journal-title":"Am J Physiol Cell Physiol"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1111\/sms.13968","article-title":"Functional and molecular adaptations of quadriceps and hamstring muscles to blood flow restricted training in patients with ACL rupture","volume":"31","author":"Kacin","year":"2021","journal-title":"Scand J Med Sci Sports."},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.ymeth.2010.02.003","article-title":"Bias in the cq value observed with hydrolysis probe based quantitative PCR can be corrected with the estimated PCR efficiency value","volume":"50","author":"Tuomi","year":"2010","journal-title":"Methods"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1093\/nar\/gkp045","article-title":"Amplification efficiency: Linking baseline and bias in the analysis of quantitative PCR data","volume":"37","author":"Ruijter","year":"2009","journal-title":"Nucleic Acids Res"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2836(05)80360-2","article-title":"Basic local alignment search tool","volume":"215","author":"Altschul","year":"1990","journal-title":"J Mol Biol"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.1982.242.3.H456","article-title":"Effects of fatty acid intermediates on na+-K+-ATPase activity of cardiac sarcolemma","volume":"242","author":"Owens","year":"1982","journal-title":"Am J Physiol"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbamem.2015.03.012","article-title":"General and specific lipid-protein interactions in Na,K-ATPase","volume":"1848","author":"Cornelius","year":"2015","journal-title":"Biochim Biophys Acta"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00133.2010","article-title":"HIF-1alpha response to hypoxia is functionally separated from the glucocorticoid stress response in the in vitro regenerating human skeletal muscle","volume":"299","author":"Pirkmajer","year":"2010","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00020.2006","article-title":"High dexamethasone concentration prevents stimulatory effects of TNF-alpha and LPS on IL-6 secretion from the precursors of human muscle regeneration","volume":"291","author":"Prelovsek","year":"2006","journal-title":"Am J Physiol Regul Integr Comp Physiol"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcb.2012.02.006","article-title":"Bidirectional crosstalk between endoplasmic reticulum stress and mTOR signaling","volume":"22","author":"Appenzeller-Herzog","year":"2012","journal-title":"Trends Cell Biol"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1101\/gad.1212704","article-title":"Upstream and downstream of mTOR","volume":"18","author":"Hay","year":"2004","journal-title":"Genes Dev"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1016\/j.phrs.2010.03.006","article-title":"Regulation of neuropathy target esterase by the cAMP\/protein kinase a signal","volume":"62","author":"Chen","year":"2010","journal-title":"Pharmacol Res"},{"key":"B44","doi-asserted-by":"publisher","first-page":"199","DOI":"10.1089\/dna.2012.1835","article-title":"CREB is required for cAMP\/PKA signals upregulating neuropathy target esterase expression","volume":"32","author":"Chen","year":"2013","journal-title":"DNA Cell Biol"},{"key":"B45","doi-asserted-by":"publisher","first-page":"848","DOI":"10.3390\/biom9120848","article-title":"Characterization of the interaction of neuropathy target esterase with the endoplasmic reticulum and lipid droplets","volume":"9","author":"Chang","year":"2019","journal-title":"Biomolecules"},{"key":"B46","doi-asserted-by":"publisher","first-page":"637","DOI":"10.3390\/metabo12070637","article-title":"The catalytic domain of neuropathy target esterase influences lipid droplet biogenesis and lipid metabolism in human neuroblastoma cells","volume":"12","author":"He","year":"2022","journal-title":"Metabolites"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M210743200","article-title":"Protein domains, catalytic activity, and subcellular distribution of neuropathy target esterase in mammalian cells","volume":"278","author":"Li","year":"2003","journal-title":"J Biol Chem"},{"key":"B48","doi-asserted-by":"publisher","first-page":"14983","DOI":"10.3390\/ijms232314983","article-title":"The patatin-like phospholipase domain containing protein 7 regulates macrophage classical activation through SIRT1\/NF-kappaB and p38 MAPK pathways","volume":"23","author":"Zhao","year":"2022","journal-title":"Int J Mol Sci"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1111\/j.1745-4514.1984.tb00318.x","article-title":"Molecular-weight of patatin, a major potato-tuber protein","volume":"8","author":"Racusen","year":"1984","journal-title":"J Food Biochem"},{"key":"B50","doi-asserted-by":"publisher","first-page":"765","DOI":"10.1038\/s41467-018-03193-0","article-title":"The structure of iPLA(2)beta reveals dimeric active sites and suggests mechanisms of regulation and localization","volume":"9","author":"Malley","year":"2018","journal-title":"Nat Commun"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.1152\/ajpcell.00540.2019","article-title":"Comparative profiling of skeletal muscle models reveals heterogeneity of transcriptome and metabolism","volume":"318","author":"Abdelmoez","year":"2019","journal-title":"Am J Physiol Cell Physiol"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2022.982842","article-title":"Energy metabolism in skeletal muscle cells from donors with different body mass index frontiers in physiology","volume":"13","author":"Katare","year":"2022","journal-title":"Front Physiol"},{"key":"B53","doi-asserted-by":"publisher","DOI":"10.1007\/s00441-013-1655-1","article-title":"Are cultured human myotubes far from home","volume":"354","author":"Aas","year":"2013","journal-title":"Cell Tissue Res"}],"container-title":["Frontiers in Endocrinology"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1139303\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,3,22]],"date-time":"2023-03-22T05:48:03Z","timestamp":1679464083000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fendo.2023.1139303\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,3,22]]},"references-count":53,"alternative-id":["10.3389\/fendo.2023.1139303"],"URL":"https:\/\/doi.org\/10.3389\/fendo.2023.1139303","relation":{},"ISSN":["1664-2392"],"issn-type":[{"value":"1664-2392","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,3,22]]},"article-number":"1139303"}}