{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T20:39:59Z","timestamp":1790714399939,"version":"4.1.0"},"reference-count":94,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T00:00:00Z","timestamp":1619049600000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Nutr."],"abstract":"<jats:p>After almost a century of misunderstanding, it is time to appreciate that lactate shuttling is an important feature of energy flux and metabolic regulation that involves a complex series of metabolic, neuroendocrine, cardiovascular, and cardiac events <jats:italic>in vivo<\/jats:italic>. Cell\u2013cell and intracellular lactate shuttles in the heart and between the heart and other tissues fulfill essential purposes of energy substrate production and distribution as well as cell signaling under fully aerobic conditions. Recognition of lactate shuttling came first in studies of physical exercise where the roles of driver (producer) and recipient (consumer) cells and tissues were obvious. One powerful example of cell\u2013cell lactate shuttling was the exchange of carbohydrate energy in the form of lactate between working limb skeletal muscle and the heart. The exchange of mass represented a conservation of mass that required the integration of neuroendocrine, autoregulatory, and cardiovascular systems. Now, with greater scrutiny and recognition of the effect of the cardiac cycle on myocardial blood flow, there brings an appreciation that metabolic fluxes must accommodate to pressure-flow realities within an organ in which they occur. Therefore, the presence of an intra-cardiac lactate shuttle is posited to explain how cardiac mechanics and metabolism are synchronized. Specifically, interruption of blood flow during the isotonic phase of systole is supported by glycolysis and subsequent return of blood flow during diastole allows for recovery sustained by oxidative metabolism.<\/jats:p>","DOI":"10.3389\/fnut.2021.663560","type":"journal-article","created":{"date-parts":[[2021,4,22]],"date-time":"2021-04-22T05:42:05Z","timestamp":1619070125000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":50,"title":["Role of the Heart in Lactate Shuttling"],"prefix":"10.3389","volume":"8","author":[{"given":"George A.","family":"Brooks","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2021,4,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"757","DOI":"10.1016\/j.cmet.2018.03.008","article-title":"The science and translation of lactate shuttle theory","volume":"27","author":"Brooks","year":"2018","journal-title":"Cell Metab."},{"key":"B2","first-page":"2924","article-title":"Lactate production under fully aerobic conditions: the lactate shuttle during rest and exercise","volume":"45","author":"Brooks","year":"1986","journal-title":"Fed Proc."},{"key":"B3","doi-asserted-by":"publisher","first-page":"478","DOI":"10.1016\/0090-1229(88)90134-1","article-title":"A second IUIS\/WHO report","volume":"49","year":"1988","journal-title":"Clin Immunol Immunopathol"},{"key":"B4","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1113\/jphysiol.2003.058701","article-title":"Lactate metabolism: a new paradigm for the third millennium","volume":"558","author":"Gladden","year":"2004","journal-title":"J Physiol."},{"key":"B5","doi-asserted-by":"publisher","first-page":"101454","DOI":"10.1016\/j.redox.2020.101454","article-title":"Lactate as a fulcrum of metabolism","volume":"35","author":"Brooks","year":"2020","journal-title":"Redox Biol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"208","DOI":"10.1007\/978-3-642-70610-3_15","article-title":"Glycolytic end product and oxidative substrate during sustained exercise in mammals\u2013the \u201clactate shuttle","author":"Brooks","year":"1984","journal-title":"Com Physiol Biochem."},{"key":"B7","doi-asserted-by":"publisher","first-page":"22","DOI":"10.1249\/00005768-198502000-00005","article-title":"Anaerobic threshold: review of the concept and directions for future research","volume":"17","author":"Brooks","year":"1985","journal-title":"Med Sci Sports Exerc."},{"key":"B8","doi-asserted-by":"publisher","first-page":"2253","DOI":"10.1152\/jappl.1994.76.6.2253","article-title":"Balance of carbohydrate and lipid utilization during exercise: the \u201ccrossover\u201d concept","volume":"76","author":"Brooks","year":"1994","journal-title":"J Appl Physiol."},{"key":"B9","doi-asserted-by":"publisher","first-page":"838","DOI":"10.1016\/j.cjca.2016.12.013","article-title":"Metabolic modulators in heart disease: past, present, and future","volume":"33","author":"Lopaschuk","year":"2017","journal-title":"Can J Cardiol."},{"key":"B10","doi-asserted-by":"publisher","first-page":"284","DOI":"10.1016\/0002-9343(53)90082-5","article-title":"Metabolic studies on the human heart in vivo. 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