title: Metabolic effects of fasting on human and mouse blood in vivo.
abstract: Starvation is a strong physiological stimulus of macroautophagy/autophagy. In this study, we addressed the question as to whether it would be possible to measure autophagy in blood cells after nutrient deprivation. Fasting of mice for 48 h (which causes ∼20% weight loss) or starvation of human volunteers for up to 4 d (which causes <2% weight loss) provokes major changes in the plasma metabolome, yet induces only relatively minor alterations in the intracellular metabolome of circulating leukocytes. White blood cells from mice and human volunteers responded to fasting with a marked reduction in protein lysine acetylation, affecting both nuclear and cytoplasmic compartments. In circulating leukocytes from mice that underwent 48-h fasting, an increase in LC3B lipidation (as assessed by immunoblotting and immunofluorescence) only became detectable if the protease inhibitor leupeptin was injected 2 h before drawing blood. Consistently, measurement of an enhanced autophagic flux was only possible if white blood cells from starved human volunteers were cultured in the presence or absence of leupeptin. Whereas all murine leukocyte subpopulations significantly increased the number of LC3B+puncta per cell in response to nutrient deprivation, only neutrophils from starved volunteers showed signs of activated autophagy (as determined by a combination of multi-color immunofluorescence, cytofluorometry and image analysis). Altogether, these results suggest that white blood cells are suitable for monitoring autophagic flux. In addition, we propose that the evaluation of protein acetylation in circulating leukocytes can be adopted as a biochemical marker of organismal energetic status.
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Federico
authors.initials: F
authors.lastname: Pietrocola
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.
authors.forename: Yohann
authors.initials: Y
authors.lastname: Demont
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.|f Sotio a.c. ; Prague , Czech Republic.
authors.forename: Francesca
authors.initials: F
authors.lastname: Castoldi
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: David
authors.initials: D
authors.lastname: Enot
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Sylvère
authors.initials: S
authors.lastname: Durand
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|e Centre d'Investigation Clinique-Unité de Recherche Clinique Paris Centre Necker-Cochin, Assistance Publique Hôpitaux de Paris , France.
authors.forename: Michaela
authors.initials: M
authors.lastname: Semeraro
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Elisa Elena
authors.initials: EE
authors.lastname: Baracco
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Jonathan
authors.initials: J
authors.lastname: Pol
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Jose Manuel
authors.initials: JM
authors.lastname: Bravo-San Pedro
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Chloé
authors.initials: C
authors.lastname: Bordenave
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Levesque
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Juliette
authors.initials: J
authors.lastname: Humeau
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: Alexis
authors.initials: A
authors.lastname: Chery
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.
authors.forename: Didier
authors.initials: D
authors.lastname: Métivier
authors.affiliation: g Institute of Molecular Biosciences, NAWI Graz, University of Graz , Graz , Austria.|h BioTechMed-Graz , Graz , Austria.
authors.forename: Frank
authors.initials: F
authors.lastname: Madeo
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.
authors.forename: M Chiara
authors.initials: MC
authors.lastname: Maiuri
authors.affiliation: a Equipe 11 labellisée Ligue contre le Cancer, Centre de Recherche des Cordeliers, INSERM U 1138 , Paris , France.|b Université Paris Descartes, Sorbonne Paris Cité , Paris , France.|c Université Pierre et Marie Curie , Paris , France.|d Metabolomics and Cell Biology Platforms, Gustave Roussy Comprehensive Cancer Institute , Villejuif , France.|i Pôle de Biologie, Hôpital Européen Georges Pompidou, AP-HP , Paris , France.|j Karolinska Institute, Department of Women's and Children's Health , Karolinska University Hospital , Stockholm , Sweden.
authors.forename: Guido
authors.initials: G
authors.lastname: Kroemer
mesh_terms: D000107:Acetylation; D000328:Adult; D000818:Animals; D001343:Autophagy; D002478:Cells, Cultured; D005215:Fasting / Q000097:blood* / Q000378:metabolism*; D005260:Female; D006801:Humans; D008239:Lysine / Q000378:metabolism; D008297:Male; D055442:Metabolome; D055432:Metabolomics; D008810:Mice, Inbred C57BL; D008875:Middle Aged; D009504:Neutrophils / Q000378:metabolism; D013217:Starvation / Q000097:blood / Q000378:metabolism; D055815:Young Adult
chemical_list: D008239:Lysine
keywords: IGF1; autophagy; caloric restriction; leukocytes; longevity; metabolome; p62; protein acetylation