2. Academic Validation
  3. Lipokine 5-PAHSA Is Regulated by Adipose Triglyceride Lipase and Primes Adipocytes for De Novo Lipogenesis in Mice

Lipokine 5-PAHSA Is Regulated by Adipose Triglyceride Lipase and Primes Adipocytes for De Novo Lipogenesis in Mice

  • Diabetes. 2020 Mar;69(3):300-312. doi: 10.2337/db19-0494.
Veronika Paluchova 1,  Marina Oseeva 1,  Marie Brezinova 1,  Tomas Cajka 1,  Kristina Bardova 1,  Katerina Adamcova 1,  Petr Zacek 2,  Kristyna Brejchova 1,  Laurence Balas 3,  Hana Chodounska 4,  Eva Kudova 4,  Renate Schreiber 5,  Rudolf Zechner 5,  Thierry Durand 3,  Martin Rossmeisl 1,  Nada A Abumrad 6,  Jan Kopecky 1,  Ondrej Kuda 7
Affiliations

Affiliations

  • 1 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic.
  • 2 Proteomics Core Facility, Faculty of Science, Charles University, Division BIOCEV, Vestec, Czech Republic.
  • 3 Institut des Biomolécules Max Mousseron, UMR 5247, CNRS, Université Montpellier, and Faculté de Pharmacie, ENSCM, Montpellier, France.
  • 4 Neurosteroids, Institute of Organic Chemistry and Biochemistry of the Czech Academy of Sciences, Prague, Czech Republic.
  • 5 Institute of Molecular Biosciences, University of Graz, Graz, Austria.
  • 6 Department of Medicine, Washington University School of Medicine, St. Louis, MO.
  • 7 Institute of Physiology of the Czech Academy of Sciences, Prague, Czech Republic ondrej.kuda@fgu.cas.cz.
PMID: 31806624 DOI: 10.2337/db19-0494
Abstract

Branched esters of palmitic acid and hydroxystearic acid (PAHSA) are anti-inflammatory and antidiabetic lipokines that connect glucose and lipid metabolism. We aimed to characterize involvement of the 5-PAHSA regioisomer in the adaptive metabolic response of white adipose tissue (WAT) to cold exposure (CE) in mice, exploring the cross talk between glucose utilization and lipid metabolism. CE promoted local production of 5- and 9-PAHSAs in WAT. Metabolic labeling of de novo lipogenesis (DNL) using 2H2O revealed that 5-PAHSA potentiated the effects of CE and stimulated triacylglycerol (TAG)/fatty acid (FA) cycling in WAT through impacting lipogenesis and lipolysis. Adipocyte lipolytic products were altered by 5-PAHSA through selective FA re-esterification. The impaired lipolysis in global adipose triglyceride Lipase (ATGL) knockout mice reduced free PAHSA levels and uncovered a metabolite reservoir of TAG-bound PAHSAs (TAG estolides) in WAT. Utilization of 13C isotope tracers and dynamic metabolomics documented that 5-PAHSA primes adipocytes for glucose metabolism in a different way from Insulin, promoting DNL and impeding TAG synthesis. In summary, our data reveal new cellular and physiological mechanisms underlying the beneficial effects of 5-PAHSA and its relation to Insulin action in adipocytes and independently confirm a PAHSA metabolite reservoir linked to ATGL-mediated lipolysis.

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