The tortuous path of lactate shuttle discovery: From cinders and boards to the lab and ICU

J Sport Health Sci. 2020 Sep;9(5):446-460. doi: 10.1016/j.jshs.2020.02.006. Epub 2020 Feb 21.

Abstract

Once thought to be a waste product of oxygen limited (anaerobic) metabolism, lactate is now known to form continuously under fully oxygenated (aerobic) conditions. Lactate shuttling between producer (driver) and consumer cells fulfills at least 3 purposes; lactate is: (1) a major energy source, (2) the major gluconeogenic precursor, and (3) a signaling molecule. The Lactate Shuttle theory is applicable to diverse fields such as sports nutrition and hydration, resuscitation from acidosis and Dengue, treatment of traumatic brain injury, maintenance of glycemia, reduction of inflammation, cardiac support in heart failure and following a myocardial infarction, and to improve cognition. Yet, dysregulated lactate shuttling disrupts metabolic flexibility, and worse, supports oncogenesis. Lactate production in cancer (the Warburg effect) is involved in all main sequela for carcinogenesis: angiogenesis, immune escape, cell migration, metastasis, and self-sufficient metabolism. The history of the tortuous path of discovery in lactate metabolism and shuttling was discussed in the 2019 American College of Sports Medicine Joseph B. Wolffe Lecture in Orlando, FL.

Keywords: Anaerobic metabolism; Exercise; Glycolysis; Oxidative metabolism, Warburg Effect.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Anaerobiosis
  • Blood Glucose / metabolism
  • Critical Care*
  • Cytosol / metabolism
  • Endurance Training
  • Fatty Acids / metabolism
  • Glycolysis
  • Humans
  • Lactic Acid / biosynthesis
  • Lactic Acid / metabolism*
  • Lactic Acid / therapeutic use*
  • Lipolysis
  • Mitochondria / metabolism
  • Monocarboxylic Acid Transporters / metabolism
  • Oxidation-Reduction
  • Oxidative Stress
  • Sepsis / therapy
  • Signal Transduction
  • Warburg Effect, Oncologic

Substances

  • Blood Glucose
  • Fatty Acids
  • Monocarboxylic Acid Transporters
  • Lactic Acid