Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice

Veronika Paluchova; Marina Oseeva; Marie Brezinova; Tomas Cajka; Kristina Bardova; Katerina Adamcova; Petr Zacek; Kristyna Brejchova; Laurence Balas; Hana Chodounska; Eva Kudova; Renate Schreiber; Rudolf Zechner; Thierry Durand; Martin Rossmeisl; Nada A. Abumrad; Jan Kopecky; Ondrej Kuda

doi:10.2337/db19-0494

Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice

Veronika Paluchova, Marina Oseeva, Marie Brezinova, Tomas Cajka, Kristina Bardova, Katerina Adamcova, Petr Zacek, Kristyna Brejchova, Laurence Balas, Hana Chodounska, Eva Kudova, Renate Schreiber, Rudolf Zechner, Thierry Durand, Martin Rossmeisl, Nada A. Abumrad, Jan Kopecky, Ondrej Kuda

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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.

Original language	English
Pages (from-to)	300-312
Number of pages	13
Journal	Diabetes
Volume	69
Issue number	3
DOIs	https://doi.org/10.2337/db19-0494
State	Published - Mar 1 2020

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Paluchova, V., Oseeva, M., Brezinova, M., Cajka, T., Bardova, K., Adamcova, K., Zacek, P., Brejchova, K., Balas, L., Chodounska, H., Kudova, E., Schreiber, R., Zechner, R., Durand, T., Rossmeisl, M., Abumrad, N. A., Kopecky, J., & Kuda, O. (2020). Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice. Diabetes, 69(3), 300-312. https://doi.org/10.2337/db19-0494

@article{309badc6dcb24ff9aad63b204f445d46,

title = "Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice",

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.",

author = "Veronika Paluchova and Marina Oseeva and Marie Brezinova and Tomas Cajka and Kristina Bardova and Katerina Adamcova and Petr Zacek and Kristyna Brejchova and Laurence Balas and Hana Chodounska and Eva Kudova and Renate Schreiber and Rudolf Zechner and Thierry Durand and Martin Rossmeisl and Abumrad, {Nada A.} and Jan Kopecky and Ondrej Kuda",

note = "Publisher Copyright: {\textcopyright} 2019 by the American Diabetes Association.",

year = "2020",

month = mar,

day = "1",

doi = "10.2337/db19-0494",

language = "English",

volume = "69",

pages = "300--312",

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Paluchova, V, Oseeva, M, Brezinova, M, Cajka, T, Bardova, K, Adamcova, K, Zacek, P, Brejchova, K, Balas, L, Chodounska, H, Kudova, E, Schreiber, R, Zechner, R, Durand, T, Rossmeisl, M, Abumrad, NA, Kopecky, J & Kuda, O 2020, 'Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice', Diabetes, vol. 69, no. 3, pp. 300-312. https://doi.org/10.2337/db19-0494

TY - JOUR

T1 - Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice

AU - Paluchova, Veronika

AU - Oseeva, Marina

AU - Brezinova, Marie

AU - Cajka, Tomas

AU - Bardova, Kristina

AU - Adamcova, Katerina

AU - Zacek, Petr

AU - Brejchova, Kristyna

AU - Balas, Laurence

AU - Chodounska, Hana

AU - Kudova, Eva

AU - Schreiber, Renate

AU - Zechner, Rudolf

AU - Durand, Thierry

AU - Rossmeisl, Martin

AU - Abumrad, Nada A.

AU - Kopecky, Jan

AU - Kuda, Ondrej

PY - 2020/3/1

Y1 - 2020/3/1

N2 - 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.

AB - 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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U2 - 10.2337/db19-0494

DO - 10.2337/db19-0494

M3 - Article

C2 - 31806624

AN - SCOPUS:85081142776

SN - 0012-1797

VL - 69

SP - 300

EP - 312

JO - Diabetes

JF - Diabetes

IS - 3

ER -

Lipokine 5-PAhsA is regulated by adipose triglyceride lipase and primes adipocytes for de novo lipogenesis in mice

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