4.6 Article

Lactate production is a prioritized feature of adipocyte metabolism

Journal

JOURNAL OF BIOLOGICAL CHEMISTRY
Volume 295, Issue 1, Pages 83-98

Publisher

ELSEVIER
DOI: 10.1074/jbc.RA119.011178

Keywords

adipocyte; insulin; insulin resistance; Drosophila; cell metabolism; metabolic regulation; fat tissue; glucose disposal; lactate; whole-body glucose homeostasis

Funding

  1. Sydney Informatics Hub - University of Sydney
  2. National Health and Medical Research Council (NHMRC) Early Career Fellowship [APP1072440]
  3. Australian Diabetes Society Skip Martin Early-Career Fellowship
  4. Diabetes Australia Research program grant
  5. CPC Early-Career Seed Funding grant
  6. Judith and David Coffey Fund
  7. Cancer Institute NSW Grant [CDF181241]
  8. University of Sydney-China Scholarship Council Postgraduate Research Scholarship [201606270221]
  9. China Scholarships Council [201708410040]
  10. Welch Foundation [I-1748]
  11. National Institutes of Health [R01GM102604]
  12. Japan Society for the Promotion of Science (JSPS) KAKENHI [JP18H04804, JP18K08219]
  13. Research on Development of New Drugs (GAPFREE) from the Japan Agency for Medical Research and Development (AMED)
  14. Yamagata prefectural government
  15. City of Tsuruoka
  16. AMED-CREST from AMED
  17. NHMRC [GNT1086850, APP1019680, GNT1061122, GNT1086851]
  18. University of Sydney Medical School

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Adipose tissue is essential for whole-body glucose homeostasis, with a primary role in lipid storage. It has been previously observed that lactate production is also an important metabolic feature of adipocytes, but its relationship to adipose and whole-body glucose disposal remains unclear. Therefore, using a combination of metabolic labeling techniques, here we closely examined lactate production of cultured and primary mammalian adipocytes. Insulin treatment increased glucose uptake and conversion to lactate, with the latter responding more to insulin than did other metabolic fates of glucose. However, lactate production did not just serve as a mechanism to dispose of excess glucose, because we also observed that lactate production in adipocytes did not solely depend on glucose availability and even occurred independently of glucose metabolism. This suggests that lactate production is prioritized in adipocytes. Furthermore, knocking down lactate dehydrogenase specifically in the fat body of Drosophila flies lowered circulating lactate and improved whole-body glucose disposal. These results emphasize that lactate production is an additional metabolic role of adipose tissue beyond lipid storage and release.

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