title: Seipin deficiency alters brown adipose tissue thermogenesis and insulin sensitivity in a non-cell autonomous mode.
abstract: Loss-of-function mutations in BSCL2 are responsible for Berardinelli-Seip congenital lipodystrophy, a rare disorder characterized by near absence of adipose tissue associated with insulin resistance. Seipin-deficient (Bscl2-/-) mice display an almost total loss of white adipose tissue (WAT) with residual brown adipose tissue (BAT). Previous cellular studies have shown that seipin deficiency alters white adipocyte differentiation. In this study, we aimed to decipher the consequences of seipin deficiency in BAT. Using a brown adipocyte cell-line, we show that seipin knockdown had very little effect on adipocyte differentiation without affecting insulin sensitivity and oxygen consumption. However, when submitted to cold acclimation or chronic β3 agonist treatment, Bscl2-/-mice displayed altered thermogenic capacity, despite several signs of BAT remodeling. Under cold activation, Bscl2-/-mice were able to maintain their body temperature when fed ad libitum, but not under short fasting. At control temperature (i.e. 21 °C), fasting worsened Bscl2-/-BAT properties. Finally, Bscl2-/-BAT displayed obvious signs of insulin resistance. Our results in these lipodystrophic mice strongly suggest that BAT activity relies on WAT as an energetic substrate provider and adipokine-producing organ. Therefore, the WAT/BAT dialogue is a key component of BAT integrity in guaranteeing its response to insulin and cold-activated adrenergic signals.
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
authors.forename: L
authors.initials: L
authors.lastname: Dollet
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
authors.forename: J
authors.initials: J
authors.lastname: Magré
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.|Endocrinologie, CHU Caen, France.
authors.forename: M
authors.initials: M
authors.lastname: Joubert
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Le May
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
authors.forename: A
authors.initials: A
authors.lastname: Ayer
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
authors.forename: L
authors.initials: L
authors.lastname: Arnaud
authors.affiliation: CRCNA UMR_S 892, Nantes, France.
authors.forename: C
authors.initials: C
authors.lastname: Pecqueur
authors.affiliation: UMR_S 1089, Nantes, France.
authors.forename: V
authors.initials: V
authors.lastname: Blouin
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, CHU Nantes, Nantes, France.
authors.forename: B
authors.initials: B
authors.lastname: Cariou
authors.affiliation: l'institut du thorax, INSERM, CNRS, UNIV Nantes, Nantes, France.
authors.forename: X
authors.initials: X
authors.lastname: Prieur
mesh_terms: D000222:Adaptation, Physiological; D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D002001:Adipose Tissue, Brown / Q000166:cytology / Q000000981:diagnostic imaging / Q000502:physiology*; D000818:Animals; D002454:Cell Differentiation / Q000235:genetics; D004195:Disease Models, Animal; D044388:GTP-Binding Protein gamma Subunits; D005947:Glucose / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000172:deficiency*; D007333:Insulin Resistance / Q000235:genetics*; D050356:Lipid Metabolism / Q000235:genetics; D008066:Lipolysis; D051379:Mice; D018345:Mice, Knockout; D000072078:Positron Emission Tomography Computed Tomography; D015398:Signal Transduction; D022722:Thermogenesis / Q000187:drug effects / Q000235:genetics*; D055114:X-Ray Microtomography
chemical_list: C115783:Bscl2 protein, mouse; D044388:GTP-Binding Protein gamma Subunits; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose