title: Cidea improves the metabolic profile through expansion of adipose tissue.
abstract: In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Gustavo
authors.initials: G
authors.lastname: Abreu-Vieira
authors.affiliation: 1] Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden [2] Department of Biochemistry and Molecular Cell Biology, University Medical Center Hamburg-Eppendorf, 20246 Hamburg, Germany.
authors.forename: Alexander W
authors.initials: AW
authors.lastname: Fischer
authors.affiliation: Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
authors.forename: Charlotte
authors.initials: C
authors.lastname: Mattsson
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Jasper M A
authors.initials: JM
authors.lastname: de Jong
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Irina G
authors.initials: IG
authors.lastname: Shabalina
authors.affiliation: Department of Medicine, Huddinge, Lipid Laboratory, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Mikael
authors.initials: M
authors.lastname: Rydén
authors.affiliation: Department of Medicine, Huddinge, Lipid Laboratory, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Jurga
authors.initials: J
authors.lastname: Laurencikiene
authors.affiliation: Department of Medicine, Huddinge, Lipid Laboratory, Karolinska Institutet, 141 86 Stockholm, Sweden.
authors.forename: Peter
authors.initials: P
authors.lastname: Arner
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Barbara
authors.initials: B
authors.lastname: Cannon
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Jan
authors.initials: J
authors.lastname: Nedergaard
authors.affiliation: Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
authors.forename: Natasa
authors.initials: N
authors.lastname: Petrovic
mesh_terms: D000273:Adipose Tissue / Q000254:growth & development* / Q000378:metabolism; D000818:Animals; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D004041:Dietary Fats / Q000008:administration & dosage; D004734:Energy Metabolism / Q000502:physiology*; D005786:Gene Expression Regulation / Q000502:physiology; D005838:Genotype; D007333:Insulin Resistance; D008264:Macrophages / Q000502:physiology; D051379:Mice; D008822:Mice, Transgenic
chemical_list: D051017:Apoptosis Regulatory Proteins; C502539:CIDEA protein, human; D004041:Dietary Fats