Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity
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Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity. / Morigny, Pauline; Houssier, Marianne; Mairal, Aline; Ghilain, Claire; Mouisel, Etienne; Benhamed, Fadila; Masri, Bernard; Recazens, Emeline; Denechaud, Pierre-Damien; Tavernier, Geneviève; Caspar-Bauguil, Sylvie; Virtue, Sam; Sramkova, Veronika; Monbrun, Laurent; Mazars, Anne; Zanoun, Madjid; Guilmeau, Sandra; Barquissau, Valentin; Beuzelin, Diane; Bonnel, Sophie; Marques, Marie; Monge-Roffarello, Boris; Lefort, Corinne; Fielding, Barbara; Sulpice, Thierry; Astrup, Arne; Payrastre, Bernard; Bertrand-Michel, Justine; Meugnier, Emmanuelle; Ligat, Laetitia; Lopez, Frédéric; Guillou, Hervé; Ling, Charlotte; Holm, Cecilia; Rabasa-Lhoret, Remi; Saris, Wim H M; Stich, Vladimir; Arner, Peter; Rydén, Mikael; Moro, Cedric; Viguerie, Nathalie; Harms, Matthew; Hallén, Stefan; Vidal-Puig, Antonio; Vidal, Hubert; Postic, Catherine; Langin, Dominique.
I: Nature Metabolism, Bind 1, Nr. 1, 2019, s. 133-146.Publikation: Bidrag til tidsskrift › Tidsskriftartikel › Forskning › fagfællebedømt
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T1 - Interaction between hormone-sensitive lipase and ChREBP in fat cells controls insulin sensitivity
AU - Morigny, Pauline
AU - Houssier, Marianne
AU - Mairal, Aline
AU - Ghilain, Claire
AU - Mouisel, Etienne
AU - Benhamed, Fadila
AU - Masri, Bernard
AU - Recazens, Emeline
AU - Denechaud, Pierre-Damien
AU - Tavernier, Geneviève
AU - Caspar-Bauguil, Sylvie
AU - Virtue, Sam
AU - Sramkova, Veronika
AU - Monbrun, Laurent
AU - Mazars, Anne
AU - Zanoun, Madjid
AU - Guilmeau, Sandra
AU - Barquissau, Valentin
AU - Beuzelin, Diane
AU - Bonnel, Sophie
AU - Marques, Marie
AU - Monge-Roffarello, Boris
AU - Lefort, Corinne
AU - Fielding, Barbara
AU - Sulpice, Thierry
AU - Astrup, Arne
AU - Payrastre, Bernard
AU - Bertrand-Michel, Justine
AU - Meugnier, Emmanuelle
AU - Ligat, Laetitia
AU - Lopez, Frédéric
AU - Guillou, Hervé
AU - Ling, Charlotte
AU - Holm, Cecilia
AU - Rabasa-Lhoret, Remi
AU - Saris, Wim H M
AU - Stich, Vladimir
AU - Arner, Peter
AU - Rydén, Mikael
AU - Moro, Cedric
AU - Viguerie, Nathalie
AU - Harms, Matthew
AU - Hallén, Stefan
AU - Vidal-Puig, Antonio
AU - Vidal, Hubert
AU - Postic, Catherine
AU - Langin, Dominique
N1 - CURIS 2019 NEXS 013
PY - 2019
Y1 - 2019
N2 - Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency–mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBPα impairs ChREBPα translocation into the nucleus and induction of ChREBPβ, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL–ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.
AB - Impaired adipose tissue insulin signalling is a critical feature of insulin resistance. Here we identify a pathway linking the lipolytic enzyme hormone-sensitive lipase (HSL) to insulin action via the glucose-responsive transcription factor ChREBP and its target, the fatty acid elongase ELOVL6. Genetic inhibition of HSL in human adipocytes and mouse adipose tissue results in enhanced insulin sensitivity and induction of ELOVL6. ELOVL6 promotes an increase in phospholipid oleic acid, which modifies plasma membrane fluidity and enhances insulin signalling. HSL deficiency–mediated effects are suppressed by gene silencing of ChREBP and ELOVL6. Mechanistically, physical interaction between HSL, independent of lipase activity, and the isoform activated by glucose metabolism ChREBPα impairs ChREBPα translocation into the nucleus and induction of ChREBPβ, the isoform with high transcriptional activity that is strongly associated with whole-body insulin sensitivity. Targeting the HSL–ChREBP interaction may allow therapeutic strategies for the restoration of insulin sensitivity.
KW - Faculty of Science
KW - Insulin resistance
KW - Hormone-sensitive lipase
KW - HSL
KW - Glucose-responsive transcription factor
KW - ChREBP
KW - Fatty acid elongase
KW - ELOVL6
KW - HSL-ChREBP interaction
KW - Therapeutic strategies
KW - Insulin sensitivity
M3 - Journal article
VL - 1
SP - 133
EP - 146
JO - Nature Metabolism
JF - Nature Metabolism
SN - 2522-5812
IS - 1
ER -
ID: 209516937