title: Fatty acids from fat cell lipolysis do not activate an inflammatory response but are stored as triacylglycerols in adipose tissue macrophages.
abstract: OBJECTIVE
  Activation of macrophages by fatty acids (FAs) is a potential mechanism linking obesity to adipose tissue (AT) inflammation and insulin resistance. Here, we investigated the effects of FAs released during adipocyte lipolysis on AT macrophages (ATMs).
  
  
  METHODS
  Human THP-1 macrophages were treated with media from human multipotent adipose-derived stem (hMADS) adipocytes stimulated with lipolytic drugs. Macrophages were also treated with mixtures of FAs and an inhibitor of Toll-like receptor 4, since this receptor is activated by saturated FAs. Levels of mRNA and the secretion of inflammation-related molecules were measured in macrophages. FA composition was determined in adipocytes, conditioned media and macrophages. The effect of chronic inhibition or acute activation of fat cell lipolysis on ATM response was investigated in vivo in mice.
  
  
  RESULTS
  Whereas palmitic acid alone activates THP-1, conditioned media from hMADS adipocyte lipolysis had no effect on IL, chemokine and cytokine gene expression, and secretion by macrophages. Mixtures of FAs representing de novo lipogenesis or habitual dietary conditions also had no effect. FAs derived from adipocyte lipolysis were taken up by macrophages and stored as triacylglycerol droplets. In vivo, chronic treatment with an antilipolytic drug did not modify gene expression and number of ATMs in mice with intact or defective Tlr4. Stimulation of adipocyte lipolysis increased storage of neutral lipids by macrophages without change in number and phenotype.
  
  
  CONCLUSIONS
  Our data suggest that adipocyte lipolysis does not activate inflammatory pathways in ATMs, which instead may act as scavengers of FAs.
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.|Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, France.
authors.forename: Sylvie
authors.initials: S
authors.lastname: Caspar-Bauguil
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Catherine-Ines
authors.initials: CI
authors.lastname: Kolditz
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Corinne
authors.initials: C
authors.lastname: Lefort
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Isabelle
authors.initials: I
authors.lastname: Vila
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Etienne
authors.initials: E
authors.lastname: Mouisel
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Diane
authors.initials: D
authors.lastname: Beuzelin
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Geneviève
authors.initials: G
authors.lastname: Tavernier
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Marie-Adeline
authors.initials: MA
authors.lastname: Marques
authors.affiliation: University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.|Inserm, UMR1048, Cytometry Facility, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.|Inserm, UMR1048, Team 1, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Alexia
authors.initials: A
authors.lastname: Zakaroff-Girard
authors.affiliation: University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.|Inserm, UMR1048, Cytometry Facility, Institute of Metabolic and Cardiovascular Diseases, Toulouse, France.
authors.forename: Christiane
authors.initials: C
authors.lastname: Pecher
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Marianne
authors.initials: M
authors.lastname: Houssier
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Lucile
authors.initials: L
authors.lastname: Mir
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Sarah
authors.initials: S
authors.lastname: Nicolas
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Moro
authors.affiliation: Inserm, UMR1048, Institute of Metabolic and Cardiovascular Diseases, I2MC, Obesity Research Laboratory, Team 4, CHU Rangueil, 1 avenue Jean Poulhès, BP 84225, 31432, Toulouse Cedex 4, France. dominique.langin@inserm.fr.|University of Toulouse, UMR1048, Paul Sabatier University, Toulouse, France. dominique.langin@inserm.fr.|Toulouse University Hospitals, Department of Clinical Biochemistry, Toulouse, France. dominique.langin@inserm.fr.
authors.forename: Dominique
authors.initials: D
authors.lastname: Langin
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism*; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D058667:Adrenergic beta-3 Receptor Agonists / Q000494:pharmacology; D000818:Animals; D002460:Cell Line; D004149:Dioxoles / Q000494:pharmacology; D005227:Fatty Acids / Q000378:metabolism* / Q000494:pharmacology; D006801:Humans; D007249:Inflammation / Q000378:metabolism; D008066:Lipolysis / Q000502:physiology*; D008264:Macrophages / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D019308:Palmitic Acid / Q000494:pharmacology; D013234:Stem Cells / Q000166:cytology / Q000378:metabolism; D051197:Toll-Like Receptor 4 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D014280:Triglycerides / Q000378:metabolism*
chemical_list: D058667:Adrenergic beta-3 Receptor Agonists; D004149:Dioxoles; D005227:Fatty Acids; D051197:Toll-Like Receptor 4; D014280:Triglycerides; C076126:disodium (R,R)-5-(2-((2-(3-chlorophenyl)-2-hydroxyethyl)-amino)propyl)-1,3-benzodioxole-2,3-dicarboxylate; D019308:Palmitic Acid
keywords: Adipocyte; Adipose tissue; De novo lipogenesis; Fatty acids; Inflammatory response; Insulin resistance; Lipolysis; Macrophage; TLR4; Triacylglycerol