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Seipin deficiency alters brown adipose tissue thermogenesis and insulin sensitivity in a non-cell autonomous mode.

Authors: Dollet, L  Magré, J  Joubert, M  Le May, C  Ayer, A  Arnaud, L  Pecqueur, C  Blouin, V  Cariou, B  Prieur, X 
Citation: Dollet L, etal., Sci Rep. 2016 Oct 17;6:35487. doi: 10.1038/srep35487.
Pubmed: (View Article at PubMed) PMID:27748422
DOI: Full-text: DOI:10.1038/srep35487

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 ß3 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.

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RGD ID: 13673869
Created: 2018-06-23
Species: All species
Last Modified: 2018-06-23
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.