title: Human Adipocytes Induce Inflammation and Atrophy in Muscle Cells During Obesity.
abstract: Inflammation and lipid accumulation are hallmarks of muscular pathologies resulting from metabolic diseases such as obesity and type 2 diabetes. During obesity, the hypertrophy of visceral adipose tissue (VAT) contributes to muscle dysfunction, particularly through the dysregulated production of adipokines. We have investigated the cross talk between human adipocytes and skeletal muscle cells to identify mechanisms linking adiposity and muscular dysfunctions. First, we demonstrated that the secretome of obese adipocytes decreased the expression of contractile proteins in myotubes, consequently inducing atrophy. Using a three-dimensional coculture of human myotubes and VAT adipocytes, we showed the decreased expression of genes corresponding to skeletal muscle contractility complex and myogenesis. We demonstrated an increased secretion by cocultured cells of cytokines and chemokines with interleukin (IL)-6 and IL-1β as key contributors. Moreover, we gathered evidence showing that obese subcutaneous adipocytes were less potent than VAT adipocytes in inducing these myotube dysfunctions. Interestingly, the atrophy induced by visceral adipocytes was corrected by IGF-II/insulin growth factor binding protein-5. Finally, we observed that the skeletal muscle of obese mice displayed decreased expression of muscular markers in correlation with VAT hypertrophy and abnormal distribution of the muscle fiber size. In summary, we show the negative impact of obese adipocytes on muscle phenotype, which could contribute to muscle wasting associated with metabolic disorders.
authors.affiliation: INSERM, U1166 Nutriomique, Paris, France Sorbonne Universités, University Pierre et Marie Curie-Paris 6, UMR S 1166, Paris, France vp332@medschl.cam.ac.uk.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Pellegrinelli
authors.affiliation: INSERM, U1166 Nutriomique, Paris, France Sorbonne Universités, University Pierre et Marie Curie-Paris 6, UMR S 1166, Paris, France Institut Cardiométabolisme et Nutrition, Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Christine
authors.initials: C
authors.lastname: Rouault
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, U.K.
authors.forename: Sergio
authors.initials: S
authors.lastname: Rodriguez-Cuenca
authors.affiliation: INSERM, U1166 Nutriomique, Paris, France Sorbonne Universités, University Pierre et Marie Curie-Paris 6, UMR S 1166, Paris, France Institut Cardiométabolisme et Nutrition, Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Victorine
authors.initials: V
authors.lastname: Albert
authors.affiliation: Sorbonne Universités, University Pierre et Marie Curie-Paris 6, Centre de Recherche en Myologie, UMR 974, Paris, France INSERM, U974, Paris, France CNRS FRE 3617, Paris, France Institut de Myologie, Paris, France.
authors.forename: Frédérique
authors.initials: F
authors.lastname: Edom-Vovard
authors.affiliation: Metabolic Research Laboratories, Wellcome Trust-MRC Institute of Metabolic Science, University of Cambridge, Cambridge, U.K.
authors.forename: Antonio
authors.initials: A
authors.lastname: Vidal-Puig
authors.affiliation: INSERM, U1166 Nutriomique, Paris, France Sorbonne Universités, University Pierre et Marie Curie-Paris 6, UMR S 1166, Paris, France Institut Cardiométabolisme et Nutrition, Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Karine
authors.initials: K
authors.lastname: Clément
authors.affiliation: Sorbonne Universités, University Pierre et Marie Curie-Paris 6, Centre de Recherche en Myologie, UMR 974, Paris, France INSERM, U974, Paris, France CNRS FRE 3617, Paris, France Institut de Myologie, Paris, France.
authors.forename: Gillian S
authors.initials: GS
authors.lastname: Butler-Browne
authors.affiliation: INSERM, U1166 Nutriomique, Paris, France Sorbonne Universités, University Pierre et Marie Curie-Paris 6, UMR S 1166, Paris, France Institut Cardiométabolisme et Nutrition, Pitié-Salpétrière Hospital, Paris, France.
authors.forename: Danièle
authors.initials: D
authors.lastname: Lacasa
mesh_terms: D017667:Adipocytes / Q000276:immunology / Q000378:metabolism*; D000328:Adult; D000818:Animals; D001284:Atrophy / Q000276:immunology / Q000378:metabolism; D018920:Coculture Techniques; D003285:Contractile Proteins / Q000378:metabolism*; D016207:Cytokines / Q000276:immunology; D005260:Female; D005786:Gene Expression Regulation; D006801:Humans; D007249:Inflammation; D018975:Insulin-Like Growth Factor Binding Protein 5 / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D016753:Interleukin-10 / Q000276:immunology / Q000378:metabolism; D053583:Interleukin-1beta / Q000276:immunology / Q000378:metabolism; D015850:Interleukin-6 / Q000276:immunology / Q000378:metabolism; D050152:Intra-Abdominal Fat / Q000166:cytology* / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008820:Mice, Obese; D018485:Muscle Fibers, Skeletal / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D009767:Obesity, Morbid / Q000276:immunology / Q000378:metabolism*; D050151:Subcutaneous Fat / Q000166:cytology / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000276:immunology / Q000378:metabolism
chemical_list: D003285:Contractile Proteins; D016207:Cytokines; C035170:IGF2 protein, human; D018975:Insulin-Like Growth Factor Binding Protein 5; D053583:Interleukin-1beta; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; D016753:Interleukin-10; D007335:Insulin-Like Growth Factor II