Cidea improves the metabolic profile through expansion of adipose tissue

  • Nat Commun. 2015 Jun 29:6:7433. doi: 10.1038/ncomms8433.
Gustavo Abreu-Vieira  1 ,  Alexander W Fischer  2 ,  Charlotte Mattsson  3 ,  Jasper M A de Jong  1 ,  Irina G Shabalina  1 ,  Mikael Rydén  4 ,  Jurga Laurencikiene  4 ,  Peter Arner  4 ,  Barbara Cannon  1 ,  Jan Nedergaard  1 ,  Natasa Petrovic  1
Affiliations
  • 1. Department of Molecular Biosciences, Wenner-Gren Institute, Arrhenius Laboratories F3, Stockholm University, 106 91 Stockholm, Sweden.
  • 2. 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.
  • 3. Department of Cell and Molecular Biology, Karolinska Institutet, 171 77 Stockholm, Sweden.
  • 4. Department of Medicine, Huddinge, Lipid Laboratory, Karolinska Institutet, 141 86 Stockholm, Sweden.
PMID: 26118629 DOI: 10.1038/ncomms8433
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.