Interaction between Hormone-Sensitive Lipase and ChREBP in Fat Cells Controls Insulin Sensitivity
Pauline Morigny
(1)
,
Marianne Houssier
(1)
,
Aline Mairal
(1)
,
Claire Ghilain
(1)
,
Etienne Mouisel
(1)
,
Fadila Benhamed
(2)
,
Bernard Masri
(1)
,
Emeline Recazens
(1)
,
Pierre-Damien Denechaud
(1)
,
Geneviève Tavernier
(1)
,
Sylvie Caspar-Bauguil
(1, 3)
,
Sam Virtue
(4)
,
Veronika Sramkova
(1, 5, 6)
,
Laurent Monbrun
(1)
,
Anne Mazars
(1)
,
Madjid Zanoun
(1)
,
Sandra Guilmeau
(2)
,
Valentin Barquissau
(1)
,
Diane Beuzelin
(1)
,
Sophie Bonnel
(1, 6)
,
Marie Marques
(1, 6)
,
Boris Monge-Roffarello
(1)
,
Corinne Lefort
(1)
,
Barbara Fielding
(7)
,
Thierry Sulpice
(8)
,
Arne Astrup
(9)
,
Bernard Payrastre
(1)
,
Justine Bertrand-Michel
(1)
,
Emmanuelle Meugnier
(10)
,
Laetitia Ligat
(11)
,
Frédéric Lopez
(11)
,
Hervé Guillou
(12)
,
Charlotte Ling
(13)
,
Cecilia Holm
(14)
,
Remi Rabasa-Lhoret
(15)
,
Rémi Rabasa-Lhoret
(15, 16, 17)
,
Wim H. M. Saris
(18)
,
Vladimir Stich
(5, 6)
,
Peter Arner
(19)
,
Mikael Rydén
(19)
,
Cédric Moro
(1, 6)
,
Nathalie Viguerie
(1, 6)
,
Matthew Harms
(20)
,
Stefan Hallén
(20)
,
Antonio Vidal-Puig
(4, 21)
,
Hubert Vidal
(10)
,
Catherine Postic
(2)
,
Dominique Langin
(1, 3, 6)
1
I2MC -
Institut des Maladies Métaboliques et Cardiovasculaires
2 IC UM3 (UMR 8104 / U1016) - Institut Cochin
3 Laboratoire de Biochimie [CHU Toulouse]
4 University of Cambridge Metabolic Research Laboratories
5 Department for the Study of Obesity and Diabetes [Prague]
6 Franco-czech Laboratory for clinical research on obesity
7 Department of Nutritional Sciences
8 Physiogenex
9 Department of Nutrition, Exercise and Sports [Copenhagen]
10 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
11 CRCT - Centre de Recherches en Cancérologie de Toulouse
12 ToxAlim-TIM - Toxicologie Intégrative & Métabolisme
13 Department of Clinical Sciences, Epigenetics and Diabetes
14 Department of Experimental Medical Science
15 IRCM - Institut de Recherches Cliniques de Montréal
16 Montreal Diabetes Research Center
17 Department of nutrition
18 Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism
19 Department of medicine [Stockholm]
20 Cardiovascular, Renal and Metabolism, IMED Biotech Unit
21 The Wellcome Trust Sanger Institute [Cambridge]
2 IC UM3 (UMR 8104 / U1016) - Institut Cochin
3 Laboratoire de Biochimie [CHU Toulouse]
4 University of Cambridge Metabolic Research Laboratories
5 Department for the Study of Obesity and Diabetes [Prague]
6 Franco-czech Laboratory for clinical research on obesity
7 Department of Nutritional Sciences
8 Physiogenex
9 Department of Nutrition, Exercise and Sports [Copenhagen]
10 CarMeN - Cardiovasculaire, métabolisme, diabétologie et nutrition
11 CRCT - Centre de Recherches en Cancérologie de Toulouse
12 ToxAlim-TIM - Toxicologie Intégrative & Métabolisme
13 Department of Clinical Sciences, Epigenetics and Diabetes
14 Department of Experimental Medical Science
15 IRCM - Institut de Recherches Cliniques de Montréal
16 Montreal Diabetes Research Center
17 Department of nutrition
18 Department of Human Biology, NUTRIM School of Nutrition and Translational Research in Metabolism
19 Department of medicine [Stockholm]
20 Cardiovascular, Renal and Metabolism, IMED Biotech Unit
21 The Wellcome Trust Sanger Institute [Cambridge]
Marianne Houssier
- Function : Author
- PersonId : 753921
- IdHAL : marianne-houssier
- ORCID : 0000-0002-5329-4597
Pierre-Damien Denechaud
- Function : Author
- PersonId : 784273
- ORCID : 0000-0003-3502-4814
- IdRef : 134731913
Corinne Lefort
- Function : Author
- PersonId : 1170554
Arne Astrup
- Function : Author
- PersonId : 756980
- ORCID : 0000-0001-8968-8996
Bernard Payrastre
- Function : Author
- PersonId : 858382
Emmanuelle Meugnier
- Function : Author
- PersonId : 171473
- IdHAL : emmanuelle-meugnier
- ORCID : 0000-0002-2291-7691
- IdRef : 253124204
Hervé Guillou
- Function : Author
- PersonId : 737297
- IdHAL : herve-guillou-inrae
Cédric Moro
- Function : Author
- PersonId : 756381
- ORCID : 0000-0003-4294-0597
- IdRef : 091491401
Stefan Hallén
- Function : Author
- PersonId : 914188
Hubert Vidal
- Function : Author
- PersonId : 21591
- IdHAL : hubert-vidal
- ORCID : 0000-0002-9467-0317
- IdRef : 034238875
Dominique Langin
Connectez-vous pour contacter l'auteur
- Function : Correspondent author
- PersonId : 175745
- IdHAL : dominique-langin
- ORCID : 0000-0002-2669-7825
- IdRef : 050475509
Connectez-vous pour contacter l'auteur
Abstract
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
Domains
Endocrinology and metabolism
Fichier principal
NatureMetabolismAcceptedVersion.pdf (2.08 Mo)
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SupplementaryInformation.pdf (13.34 Mo)
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