{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,15]],"date-time":"2026-05-15T19:39:04Z","timestamp":1778873944284,"version":"3.51.4"},"reference-count":92,"publisher":"MDPI AG","issue":"21","license":[{"start":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T00:00:00Z","timestamp":1604793600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100005297","name":"Uniwersytet Medyczny w Bialymstoku","doi-asserted-by":"publisher","award":["SUB\/1\/DN\/19\/005\/1118"],"award-info":[{"award-number":["SUB\/1\/DN\/19\/005\/1118"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100005297","name":"Uniwersytet Medyczny w Bialymstoku","doi-asserted-by":"publisher","award":["N\/ST\/ZB\/18\/003\/1118"],"award-info":[{"award-number":["N\/ST\/ZB\/18\/003\/1118"]}],"id":[{"id":"10.13039\/501100005297","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100014269","name":"Uniwersytet Medyczny w Bia\u0142ymstoku","doi-asserted-by":"publisher","award":["SUB\/1\/DN\/20\/011\/1118"],"award-info":[{"award-number":["SUB\/1\/DN\/20\/011\/1118"]}],"id":[{"id":"10.13039\/501100014269","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>Pyrroloquinoline quinone (PQQ) is a novel stimulator of mitochondrial biogenesis and cellular energy metabolism. This is the first study investigating regulatory mechanisms and metabolic responses underlying PQQ\u2019s action in palmitate-exposed L6 myotubes. Particularly, we assessed alterations in lipid content and composition, expression of metabolic enzymes, and changes in glucose transport. The experiments were conducted using muscle cells subjected to short (2 h) and prolonged (24 h) incubation with PQQ in a sequence of pre- and post-palmitic acid (PA) exposure. We demonstrated the opposite effects of 2 and 24 h treatments with PQQ on lipid content, i.e., a decline in the level of free fatty acids and triacylglycerols in response to short-time PQQ incubation as compared to increases in diacylglycerol and triacylglycerol levels observed after 24 h. We did not demonstrate a significant impact of PQQ on fatty acid transport. The analysis of metabolic enzyme expression showed that the vast majority of PQQ-dependent alterations cumulated in the PA\/PQQ 24 h group, including elevated protein amount of peroxisome proliferator activated receptor \u03b3 co-activator 1\u03b1 (PGC-1\u03b1), sirtuin-1 (SIRT1), phosphorylated 5\u2032AMP-activated protein kinase (pAMPK), carnitine palmitoyltransferase I (CPT1), citrate synthase (CS), fatty acid synthase (FAS), and serine palmitoyltransferase, long chain base subunit 1 (SPT1). In conclusion, the results mentioned above indicate PQQ-dependent activation of both fatty acid oxidation and lipid synthesis in order to adapt cells to palmitic acid-rich medium, although PQQ did not attenuate insulin resistance in muscle cells.<\/jats:p>","DOI":"10.3390\/ijms21218382","type":"journal-article","created":{"date-parts":[[2020,11,8]],"date-time":"2020-11-08T19:03:37Z","timestamp":1604862217000},"page":"8382","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":10,"title":["Pyrroloquinoline Quinone Modifies Lipid Profile, but Not Insulin Sensitivity, of Palmitic Acid-Treated L6 Myotubes"],"prefix":"10.3390","volume":"21","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-3595-4707","authenticated-orcid":false,"given":"El\u017cbieta","family":"Supruniuk","sequence":"first","affiliation":[{"name":"Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4936-3120","authenticated-orcid":false,"given":"Agnieszka","family":"Mik\u0142osz","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7407-8156","authenticated-orcid":false,"given":"Adrian","family":"Chabowski","sequence":"additional","affiliation":[{"name":"Department of Physiology, Medical University of Bialystok, Mickiewicza 2C Street, 15-222 Bialystok, Poland"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2020,11,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Olaogun, I., Farag, M., and Hamid, P. (2020). The pathophysiology of type 2 diabetes mellitus in non-obese individuals: An overview of the current understanding. Cureus, 12.","DOI":"10.7759\/cureus.7614"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1186\/s13098-020-0523-x","article-title":"Mechanism of increased risk of insulin resistance in aging skeletal muscle","volume":"12","author":"Shou","year":"2020","journal-title":"Diabetol. Metab. Syndr."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1600","DOI":"10.2337\/diabetes.48.8.1600","article-title":"Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans: A 1H-13C nuclear magnetic resonance spectroscopy assessment in offspring of type 2 diabetic parents","volume":"48","author":"Perseghin","year":"1999","journal-title":"Diabetes"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"1113","DOI":"10.2337\/diabetes.48.5.1113","article-title":"Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects","volume":"48","author":"Jacob","year":"1999","journal-title":"Diabetes"},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"345","DOI":"10.1016\/j.plefa.2007.10.017","article-title":"Evidence for concerted action of FAT\/CD36 and FABPpm to increase fatty acid transport across the plasma membrane","volume":"77","author":"Chabowski","year":"2007","journal-title":"Prostaglandins Leukot. Essent. Fat. Acids"},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"1444","DOI":"10.1210\/en.2012-2029","article-title":"High-fat diet-mediated lipotoxicity and insulin resistance is related to impaired lipase expression in mouse skeletal muscle","volume":"154","author":"Badin","year":"2013","journal-title":"Endocrinology"},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1638","DOI":"10.1007\/s00125-013-2913-1","article-title":"Distinct patterns of tissue-specific lipid accumulation during the induction of insulin resistance in mice by high-fat feeding","volume":"56","author":"Turner","year":"2013","journal-title":"Diabetologia"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"618","DOI":"10.1016\/j.tem.2019.06.005","article-title":"Reassessing the role of diacylglycerols in insulin resistance","volume":"30","author":"Jayasinghe","year":"2019","journal-title":"Trends Endocrinol. Metab."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"R65","DOI":"10.1530\/JME-18-0023","article-title":"Defining lipid mediators of insulin resistance: Controversies and challenges","volume":"62","author":"Metcalfe","year":"2019","journal-title":"J. Mol. Endocrinol."},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"427","DOI":"10.1042\/BJ20130807","article-title":"Mitochondrial fission mediates ceramide-induced metabolic disruption in skeletal muscle","volume":"456","author":"Smith","year":"2013","journal-title":"Biochem. J."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"1","DOI":"10.3389\/fendo.2019.00577","article-title":"The role of ceramides in insulin resistance","volume":"10","author":"Sokolowska","year":"2019","journal-title":"Front. Endocrinol. (Lausanne)"},{"key":"ref_12","doi-asserted-by":"crossref","unstructured":"Li, X., Li, Z., Zhao, M., Nie, Y., Liu, P., Zhu, Y., and Zhang, X. (2019). Skeletal muscle lipid droplets and the athlete\u2019s paradox. Cells, 8.","DOI":"10.3390\/cells8030249"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"843","DOI":"10.1038\/280843a0","article-title":"A novel coenzyme from bacterial primary alcohol dehydrogenases","volume":"280","author":"Salisbury","year":"1979","journal-title":"Nature"},{"key":"ref_14","first-page":"268","article-title":"Potential physiological importance of pyrroloquinoline quinone","volume":"14","author":"Rucker","year":"2009","journal-title":"Altern. Med. Rev."},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"331","DOI":"10.1042\/bj3070331","article-title":"Levels of pyrroloquinoline quinone in various foods","volume":"307","author":"Kumazawa","year":"1995","journal-title":"Biochem. J."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"2076","DOI":"10.1016\/j.jnutbio.2013.07.008","article-title":"Dietary pyrroloquinoline quinone (PQQ) alters indicators of inflammation and mitochondrial-related metabolism in human subjects","volume":"24","author":"Harris","year":"2013","journal-title":"J. Nutr. Biochem."},{"key":"ref_17","first-page":"873","article-title":"Pyrroloquinoline quinone attenuates isoproterenol hydrochloride-induced cardiac hypertrophy in AC16 cells by inhibiting the NF-\u03baB signaling pathway","volume":"45","author":"Wen","year":"2020","journal-title":"Int. J. Mol. Med."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"440","DOI":"10.21037\/atm.2019.08.101","article-title":"PQQ ameliorates skeletal muscle atrophy, mitophagy and fiber type transition induced by denervation via inhibition of the inflammatory signaling pathways","volume":"7","author":"Ma","year":"2019","journal-title":"Ann. Transl. Med."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1080\/09168451.2015.1062715","article-title":"Recent progress in studies on the health benefits of pyrroloquinoline quinone","volume":"80","author":"Akagawa","year":"2016","journal-title":"Biosci. Biotechnol. Biochem."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1007\/s11010-013-1849-6","article-title":"Pyrroloquinoline quinone inhibits oxygen\/glucose deprivation-induced apoptosis by activating the PI3K\/AKT pathway in cardiomyocytes","volume":"386","author":"Xu","year":"2014","journal-title":"Mol. Cell. Biochem."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"313","DOI":"10.1007\/s12038-012-9195-5","article-title":"Pyrroloquinoline-quinone and its versatile roles in biological processes","volume":"37","author":"Misra","year":"2012","journal-title":"J. Biosci."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"8432","DOI":"10.1021\/acs.inorgchem.9b00568","article-title":"Studies of redox cofactor pyrroloquinoline quinone and its interaction with lanthanides(III) and calcium(II)","volume":"58","author":"Lumpe","year":"2019","journal-title":"Inorg. Chem."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"1705","DOI":"10.1021\/jf104420y","article-title":"Kinetic study of the quenching reaction of singlet oxygen by pyrroloquinolinequinol (PQQH2, a reduced form of pyrroloquinolinequinone) in micellar solution","volume":"59","author":"Mukai","year":"2011","journal-title":"J. Agric. Food Chem."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"738","DOI":"10.1080\/07315724.2018.1461146","article-title":"Mechanisms behind pyrroloquinoline quinone supplementation on skeletal muscle mitochondrial biogenesis: Possible synergistic effects with exercise","volume":"37","author":"Hwang","year":"2018","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_25","doi-asserted-by":"crossref","first-page":"142","DOI":"10.1074\/jbc.M109.030130","article-title":"Pyrroloquinoline quinone stimulates mitochondrial biogenesis through cAMP response element-binding protein phosphorylation and increased PGC-1alpha expression","volume":"285","author":"Chowanadisai","year":"2010","journal-title":"J. Biol. Chem."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"307","DOI":"10.1016\/S1097-2765(00)00031-9","article-title":"Direct coupling of transcription and mRNA processing through the thermogenic coactivator PGC-1","volume":"6","author":"Monsalve","year":"2000","journal-title":"Mol. Cell"},{"key":"ref_27","doi-asserted-by":"crossref","first-page":"441","DOI":"10.1016\/j.metabol.2014.01.006","article-title":"The many roles of PGC-1\u03b1 in muscle - Recent developments","volume":"63","author":"Chan","year":"2014","journal-title":"Metabolism"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"1434","DOI":"10.1096\/fj.201600906R","article-title":"Early PQQ supplementation has persistent long-term protective effects on developmental programming of hepatic lipotoxicity and inflammation in obese mice","volume":"31","author":"Jonscher","year":"2017","journal-title":"FASEB J."},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"11923","DOI":"10.1002\/jcp.27872","article-title":"Dose- and time-dependent alterations in lipid metabolism after pharmacological PGC-1\u03b1 activation in L6 myotubes","volume":"234","author":"Supruniuk","year":"2019","journal-title":"J. Cell. Physiol."},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"731","DOI":"10.2217\/clp.10.51","article-title":"Fatty acid transport in skeletal muscle: Role in energy provision and insulin resistance","volume":"5","author":"Holloway","year":"2010","journal-title":"Clin. Lipidol."},{"key":"ref_31","first-page":"1056","article-title":"AMPK regulates energy expenditure by modulating NAD+ metabolism and SIRT1 activity","volume":"458","author":"Feige","year":"2013","journal-title":"Nature"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"E751","DOI":"10.1152\/ajpendo.00745.2009","article-title":"AMPK and SIRT1: A long-standing partnership?","volume":"298","author":"Ruderman","year":"2010","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_33","doi-asserted-by":"crossref","unstructured":"Hong, Y.B., Lee, J.H., Park, J.M., Choi, Y.R., Hyun, Y.S., Yoon, B.R., Yoo, J.H., Koo, H., Jung, S.C., and Chung, K.W. (2013). A compound heterozygous mutation in HADHB gene causes an axonal Charcot-Marie-tooth disease. BMC Med. Genet., 14.","DOI":"10.1186\/1471-2350-14-125"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.abb.2018.08.001","article-title":"Role of DGAT enzymes in triacylglycerol metabolism","volume":"655","author":"Jordan","year":"2018","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"535","DOI":"10.1016\/j.cell.2016.03.014","article-title":"On the dependency of cellular protein levels on mRNA abundance","volume":"165","author":"Liu","year":"2016","journal-title":"Cell"},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"855","DOI":"10.15252\/msb.20156423","article-title":"Differential dynamics of the mammalian mRNA and protein expression response to misfolding stress","volume":"12","author":"Cheng","year":"2016","journal-title":"Mol. Syst. Biol."},{"key":"ref_37","doi-asserted-by":"crossref","unstructured":"Stierwalt, H.D., Ehrlicher, S.E., Bergman, B.C., Robinson, M.M., and Newsom, S.A. (2018). Insulin-stimulated Rac1-GTP binding is not impaired by palmitate treatment in L6 myotubes. Physiol. Rep., 6.","DOI":"10.14814\/phy2.13956"},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1016\/j.exger.2015.04.001","article-title":"Pyrroloquinoline quinone (PQQ) producing Escherichia coli Nissle 1917 (EcN) alleviates age associated oxidative stress and hyperlipidemia, and improves mitochondrial function in ageing rats","volume":"66","author":"Singh","year":"2015","journal-title":"Exp. Gerontol."},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"515","DOI":"10.1042\/BJ20091649","article-title":"Identification of transcriptional networks responding to pyrroloquinoline quinone dietary supplementation and their influence on thioredoxin expression, and the JAK\/STAT and MAPK pathways","volume":"429","author":"Tchaparian","year":"2010","journal-title":"Biochem. J."},{"key":"ref_40","doi-asserted-by":"crossref","unstructured":"Yamada, Y., Nishii, K., Kuwata, K., Nakamichi, M., Nakanishi, K., Sugimoto, A., and Ikemoto, K. (2020). Effects of pyrroloquinoline quinone and imidazole pyrroloquinoline on biological activities and neural functions. Heliyon, 6.","DOI":"10.1016\/j.heliyon.2020.e03240"},{"key":"ref_41","doi-asserted-by":"crossref","unstructured":"Kuo, Y.T., Shih, P.H., Kao, S.H., Yeh, G.C., and Lee, H.M. (2015). Pyrroloquinoline quinone resists denervation-induced skeletal muscle atrophy by activating PGC-1\u03b1 and integrating mitochondrial electron transport chain complexes. PLoS ONE, 10.","DOI":"10.1371\/journal.pone.0143600"},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"547","DOI":"10.1080\/07315724.2019.1705203","article-title":"Effects of pyrroloquinoline quinone (PQQ) supplementation on aerobic exercise performance and indices of mitochondrial biogenesis in untrained men","volume":"39","author":"Hwang","year":"2020","journal-title":"J. Am. Coll. Nutr."},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"844","DOI":"10.1016\/j.nutres.2015.06.014","article-title":"Pyrroloquinoline quinone increases the expression and activity of Sirt1 and -3 genes in HepG2 cells","volume":"35","author":"Zhang","year":"2015","journal-title":"Nutr. Res."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"337","DOI":"10.1038\/nature10098","article-title":"Global quantification of mammalian gene expression control","volume":"473","author":"Busse","year":"2011","journal-title":"Nature"},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"923","DOI":"10.3389\/fphys.2017.00923","article-title":"The implication of PGC-1\u03b1 on fatty acid transport across plasma and mitochondrial membranes in the insulin sensitive tissues","volume":"8","author":"Supruniuk","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"12017","DOI":"10.1073\/pnas.0705070104","article-title":"AMP-activated protein kinase (AMPK) action in skeletal muscle via direct phosphorylation of PGC-1\u03b1","volume":"104","author":"Handschin","year":"2007","journal-title":"Proc. Natl. Acad. Sci. USA"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"6615","DOI":"10.1021\/acs.biochem.7b01185","article-title":"Pyrroloquinoline Quinone, a Redox-Active o-Quinone, Stimulates Mitochondrial Biogenesis by Activating the SIRT1\/PGC-1\u03b1 Signaling Pathway","volume":"56","author":"Saihara","year":"2017","journal-title":"Biochemistry"},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"366","DOI":"10.1113\/EP086074","article-title":"AMPK does not play a requisite role in regulation of PPARGC1A gene expression via the alternative promoter in endurance-trained human skeletal muscle","volume":"102","author":"Popov","year":"2017","journal-title":"Exp. Physiol."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"1","DOI":"10.14814\/phy2.12844","article-title":"Impact of adrenaline and metabolic stress on exercise-induced intracellular signaling and PGC-1\u03b1 mRNA response in human skeletal muscle","volume":"4","author":"Brandt","year":"2016","journal-title":"Physiol. Rep."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"87","DOI":"10.14348\/molcells.2016.2318","article-title":"Sirt1 and the mitochondria","volume":"39","author":"Tang","year":"2016","journal-title":"Mol. Cells"},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"390","DOI":"10.1093\/jn\/136.2.390","article-title":"Pyrroloquinoline quinone modulates mitochondrial quantity and function in mice","volume":"136","author":"Stites","year":"2006","journal-title":"J. Nutr."},{"key":"ref_52","doi-asserted-by":"crossref","unstructured":"Bauerly, K., Harris, C., Chowanadisai, W., Graham, J., Havel, P.J., Tchaparian, E., Satre, M., Karliner, J.S., and Rucker, R.B. (2011). Altering pyrroloquinoline quinone nutritional status modulates mitochondrial, lipid, and energy metabolism in rats. PLoS ONE, 6.","DOI":"10.1371\/journal.pone.0021779"},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"901","DOI":"10.1016\/j.bbalip.2017.05.011","article-title":"Mitochondria and endoplasmic reticulum: Targets for a better insulin sensitivity in skeletal muscle?","volume":"1862","author":"Boulinguiez","year":"2017","journal-title":"Biochim. Biophys. Acta Mol. Cell Biol. Lipids"},{"key":"ref_54","doi-asserted-by":"crossref","first-page":"15169","DOI":"10.1074\/jbc.M115.705822","article-title":"Peroxisome proliferator-activated receptor \u03b3 coactivator-1 \u03b1 isoforms selectively regulate multiple splicing events on target genes","volume":"291","author":"Jannig","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_55","first-page":"44","article-title":"Resveratrol attenuates triglyceride accumulation associated with upregulation of Sirt1 and lipoprotein lipase in 3T3-L1 adipocytes","volume":"12","author":"Imamura","year":"2017","journal-title":"Mol. Genet. Metab. Rep."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"E253","DOI":"10.1152\/ajpendo.00331.2016","article-title":"Overexpression of PGC-1\u03b1 increases peroxisomal activity and mitochondrial fatty acid oxidation in human primary myotubes","volume":"312","author":"Huang","year":"2017","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"1","DOI":"10.1038\/srep26723","article-title":"Identification of lactate dehydrogenase as a mammalian pyrroloquinoline quinone (PQQ)-binding protein","volume":"6","author":"Akagawa","year":"2016","journal-title":"Sci. Rep."},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"E423","DOI":"10.1152\/ajpendo.00133.2016","article-title":"Targeting ceramide metabolism in obesity","volume":"311","author":"Aburasayn","year":"2016","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"27","DOI":"10.1016\/j.tibs.2006.11.004","article-title":"Diacylglycerol, when simplicity becomes complex","volume":"32","author":"Carrasco","year":"2007","journal-title":"Trends Biochem. Sci."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"1205","DOI":"10.1111\/obr.12862","article-title":"Lipotoxicity plays a key role in the development of both insulin resistance and muscle atrophy in patients with type 2 diabetes","volume":"20","author":"Meex","year":"2019","journal-title":"Obes. Rev."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"1026","DOI":"10.1002\/jcp.22812","article-title":"Enhanced lipid-but not carbohydrate-supported mitochondrial respiration in skeletal muscle of PGC-1\u03b1 overexpressing mice","volume":"227","author":"Hoeks","year":"2012","journal-title":"J. Cell. Physiol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"2451","DOI":"10.1016\/j.bpj.2016.04.041","article-title":"The flip-flop diffusion mechanism across lipids in a hybrid bilayer membrane","volume":"110","author":"Barile","year":"2016","journal-title":"Biophys. J."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"23","DOI":"10.1007\/s40279-015-0394-8","article-title":"The physiological regulation of skeletal muscle fatty acid supply and oxidation during moderate-intensity exercise","volume":"45","year":"2015","journal-title":"Sport Med."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"367","DOI":"10.1152\/physrev.00003.2009","article-title":"Membrane fatty acid transporters as regulators of lipid metabolism: Implications for metabolic disease","volume":"90","author":"Glatz","year":"2010","journal-title":"Physiol. Rev."},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"2283","DOI":"10.1194\/jlr.R800018-JLR200","article-title":"DGAT enzymes and triacylglycerol biosynthesis","volume":"49","author":"Yen","year":"2008","journal-title":"J. Lipid Res."},{"key":"ref_66","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1104\/pp.17.00934","article-title":"Diacylglycerol acyltransferase 1 is regulated by its N-terminal domain in response to allosteric effectors","volume":"175","author":"Caldo","year":"2017","journal-title":"Plant Physiol."},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"6888","DOI":"10.1158\/0008-5472.CAN-11-1011","article-title":"PGC-1\u03b1 promotes tumor growth by inducing gene expression programs supporting lipogenesis","volume":"71","author":"Bhalla","year":"2011","journal-title":"Cancer Res."},{"key":"ref_68","doi-asserted-by":"crossref","first-page":"1532","DOI":"10.2337\/db14-0827","article-title":"Muscle-specific overexpression of PGC-1\u03b1 does not augment metabolic improvements in response to exercise and caloric restriction","volume":"64","author":"Wong","year":"2015","journal-title":"Diabetes"},{"key":"ref_69","doi-asserted-by":"crossref","first-page":"85","DOI":"10.2337\/db12-0291","article-title":"PGC-1\u03b1 improves glucose homeostasis in skeletal muscle in an activity-dependent manner","volume":"62","author":"Summermatter","year":"2013","journal-title":"Diabetes"},{"key":"ref_70","doi-asserted-by":"crossref","first-page":"E152","DOI":"10.1152\/ajpendo.00142.2017","article-title":"Intramuscular triglyceride synthesis: Importance in muscle lipid partitioning in humans","volume":"314","author":"Bergman","year":"2018","journal-title":"Am. J. Physiol. Endocrinol. Metab."},{"key":"ref_71","doi-asserted-by":"crossref","unstructured":"Perreault, L., Newsom, S.A., Strauss, A., Kerege, A., Kahn, D.E., Harrison, K.A., Snell-Bergeon, J.K., Nemkov, T., D\u2019Alessandro, A., and Jackman, M.R. (2018). Intracellular localization of diacylglycerols and sphingolipids influences insulin sensitivity and mitochondrial function in human skeletal muscle. JCI Insight, 3.","DOI":"10.1172\/jci.insight.96805"},{"key":"ref_72","first-page":"648","article-title":"Impact on fatty acid metabolism and differential localization of FATP1 and FAT\/CD36 proteins delivered in cultured human muscle cells","volume":"288","author":"Marotta","year":"2005","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_73","doi-asserted-by":"crossref","first-page":"1323","DOI":"10.1194\/jlr.M091942","article-title":"Accumulation of saturated intramyocellular lipid is associated with insulin resistance","volume":"60","author":"Savage","year":"2019","journal-title":"J. Lipid Res."},{"key":"ref_74","doi-asserted-by":"crossref","first-page":"2588","DOI":"10.2337\/db10-1221","article-title":"Skeletal muscle triglycerides, diacylglycerols, and ceramides in insulin resistance: Another paradox in endurance-trained athletes?","volume":"60","author":"Amati","year":"2011","journal-title":"Diabetes"},{"key":"ref_75","doi-asserted-by":"crossref","first-page":"278","DOI":"10.1016\/j.cbi.2015.08.027","article-title":"Pyrroloquinoline quinone (PQQ) has potential to ameliorate streptozotocin-induced diabetes mellitus and oxidative stress in mice: A histopathological and biochemical study","volume":"240","author":"Kumar","year":"2015","journal-title":"Chem. Biol. Interact."},{"key":"ref_76","doi-asserted-by":"crossref","unstructured":"Kumar, N. (2017). Effects of pyrroloquinoline quinone and vitamin C on diabetes associated cardiac oxidative damages and hyperlipidemia in mice: Biochemical and histopathological study. MOJ Bioequiv. Bioavailab., 4.","DOI":"10.15406\/mojbb.2017.04.00059"},{"key":"ref_77","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1016\/j.bbrc.2012.10.055","article-title":"Pyrroloquinoline quinone, a novel protein tyrosine phosphatase 1B inhibitor, activates insulin signaling in C2C12 myotubes and improves impaired glucose tolerance in diabetic KK-Ay mice","volume":"428","author":"Takada","year":"2012","journal-title":"Biochem. Biophys. Res. Commun."},{"key":"ref_78","doi-asserted-by":"crossref","first-page":"160","DOI":"10.1177\/153537020322800205","article-title":"Pyrroloquinoline quinone improves growth and reproductive performance in mice fed chemically defined diets","volume":"228","author":"Steinberg","year":"2003","journal-title":"Exp. Biol. Med."},{"key":"ref_79","doi-asserted-by":"crossref","first-page":"719","DOI":"10.1093\/jn\/130.4.719","article-title":"Physiological importance of quinoenzymes and the O-quinone family of cofactors","volume":"130","author":"Stites","year":"2000","journal-title":"J. Nutr."},{"key":"ref_80","doi-asserted-by":"crossref","first-page":"317","DOI":"10.1006\/abio.1999.4039","article-title":"Characterization of pyrroloquinoline quinone amino acid derivatives by electrospray ionization mass spectrometry and detection in human milk","volume":"269","author":"Mitchell","year":"1999","journal-title":"Anal. Biochem."},{"key":"ref_81","doi-asserted-by":"crossref","first-page":"225","DOI":"10.1016\/0021-9673(93)80663-S","article-title":"Separation of amino acid-oxazole derivatives of the redox coenzyme pyrroloquinoline quinone by capillary zone electrophoresis","volume":"652","author":"Esaka","year":"1993","journal-title":"J. Chromatogr. A"},{"key":"ref_82","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1016\/j.ab.2009.10.036","article-title":"A robust assay measuring GLUT4 translocation in rat myoblasts overexpressing GLUT4-myc and AS160_v2","volume":"397","author":"Baus","year":"2010","journal-title":"Anal. Biochem."},{"key":"ref_83","doi-asserted-by":"crossref","first-page":"C1171","DOI":"10.1152\/ajpcell.00514.2009","article-title":"A role for AMPK in increased insulin action after serum starvation","volume":"299","author":"Ching","year":"2010","journal-title":"Am. J. Physiol. Cell Physiol."},{"key":"ref_84","doi-asserted-by":"crossref","first-page":"1909","DOI":"10.1016\/0024-3205(93)90631-C","article-title":"Effects of pyrroloquinoline quinone (PQQ) and PQQ-oxazole on DNA synthesis of cultured human fibroblasts","volume":"52","author":"Naito","year":"1993","journal-title":"Life Sci."},{"key":"ref_85","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1016\/S0006-2952(02)01453-3","article-title":"Antioxidant and pro-oxidant properties of pyrroloquinoline quinone (PQQ): Implications for its function in biological systems","volume":"65","author":"He","year":"2003","journal-title":"Biochem. Pharmacol."},{"key":"ref_86","doi-asserted-by":"crossref","first-page":"27","DOI":"10.3181\/00379727-197-43219","article-title":"Intestinal Absorption and Tissue Distribution of [14C]Pyrroloquinoline Quinone in Mice","volume":"197","author":"Smidt","year":"1991","journal-title":"Proc. Soc. Exp. Biol. Med."},{"key":"ref_87","doi-asserted-by":"crossref","first-page":"45e","DOI":"10.1093\/nar\/29.9.e45","article-title":"A new mathematical model for relative quantification in real-time RT-PCR","volume":"29","author":"Pfaffl","year":"2001","journal-title":"Nucleic Acids Res."},{"key":"ref_88","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1016\/j.abb.2003.08.020","article-title":"Characterizing the effects of saturated fatty acids on insulin signaling and ceramide and diacylglycerol accumulation in 3T3-L1 adipocytes and C2C12 myotubes","volume":"419","author":"Chavez","year":"2003","journal-title":"Arch. Biochem. Biophys."},{"key":"ref_89","doi-asserted-by":"crossref","first-page":"911","DOI":"10.1139\/y59-099","article-title":"A rapid method of total lipid extraction and purification","volume":"37","author":"Bligh","year":"1959","journal-title":"Can. J. Biochem. Physiol."},{"key":"ref_90","doi-asserted-by":"crossref","first-page":"600","DOI":"10.1016\/S0022-2275(20)40190-7","article-title":"Preparation of fatty acid methyl esters and dimethylacetals from lipids with boron fluoride - methanol","volume":"5","author":"Morrison","year":"1964","journal-title":"J. Lipid Res."},{"key":"ref_91","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1016\/S0022-2275(20)38081-0","article-title":"A simple procedure for rapid transmethylation of glycerolipids and cholesteryl esters","volume":"23","author":"Christie","year":"1982","journal-title":"J. Lipid Res."},{"key":"ref_92","doi-asserted-by":"crossref","first-page":"267","DOI":"10.1159\/000438628","article-title":"The effects of AS160 modulation on fatty acid transporters expression and lipid Profile in L6 myotubes","volume":"38","author":"Kurek","year":"2016","journal-title":"Cell. Physiol. Biochem."}],"container-title":["International Journal of Molecular Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8382\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:30:51Z","timestamp":1760178651000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1422-0067\/21\/21\/8382"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,11,8]]},"references-count":92,"journal-issue":{"issue":"21","published-online":{"date-parts":[[2020,11]]}},"alternative-id":["ijms21218382"],"URL":"https:\/\/doi.org\/10.3390\/ijms21218382","relation":{},"ISSN":["1422-0067"],"issn-type":[{"value":"1422-0067","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,11,8]]}}}