2. Academic Validation
  3. Lactate production is a prioritized feature of adipocyte metabolism

Lactate production is a prioritized feature of adipocyte metabolism

  • J Biol Chem. 2020 Jan 3;295(1):83-98. doi: 10.1074/jbc.RA119.011178.
James R Krycer 1,  Lake-Ee Quek 2,  Deanne Francis 1,  Daniel J Fazakerley 3,  Sarah D Elkington 1,  Alexis Diaz-Vegas 1,  Kristen C Cooke 1,  Fiona C Weiss 1,  Xiaowen Duan 1,  Sergey Kurdyukov 1,  Ping-Xin Zhou 4,  Uttam K Tambar 5,  Akiyoshi Hirayama 6,  Satsuki Ikeda 7,  Yushi Kamei 7,  Tomoyoshi Soga 6,  Gregory J Cooney 8,  David E James 9
Affiliations

Affiliations

  • 1 School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales 2006, Australia.
  • 2 Charles Perkins Centre, The University of Sydney, Sydney, New South Wales 2006, Australia; School of Mathematics and Statistics, The University of Sydney, Sydney, New South Wales 2006, Australia.
  • 3 School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales 2006, Australia; Metabolic Research Laboratories, Wellcome Trust-Medical Research Council Institute of Metabolic Science, University of Cambridge, Cambridge, CB2 0QQ, United Kingdom.
  • 4 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038; School of Basic Medical Sciences, Xinxiang Medical University, Xinxiang, Henan 453003, China.
  • 5 Department of Biochemistry, University of Texas Southwestern Medical Center, Dallas, Texas 75390-9038.
  • 6 Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan; AMED-CREST, Japan Agency for Medical Research and Development (AMED), 1-7-1 Otemachi, Chiyoda-Ku, Tokyo 100-0004, Japan.
  • 7 Institute for Advanced Biosciences, Keio University, Tsuruoka, Yamagata 997-0052, Japan.
  • 8 Charles Perkins Centre, The University of Sydney, Sydney, New South Wales 2006, Australia; Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: gregory.cooney@sydney.edu.au.
  • 9 School of Life and Environmental Sciences, The University of Sydney, Sydney, New South Wales 2006, Australia; Charles Perkins Centre, The University of Sydney, Sydney, New South Wales 2006, Australia; Sydney Medical School, The University of Sydney, Sydney, New South Wales 2006, Australia. Electronic address: david.james@sydney.edu.au.
PMID: 31690627 DOI: 10.1074/jbc.RA119.011178
Abstract

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.

Keywords

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

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