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Pannexin 1 and Pannexin 3 regulate body fat accumulation in mouse models of dietinduced obesity
Author(s) -
Penuela Silvia,
Lee Vanessa R,
Barr Kevin,
Kelly John J,
Johnston Danielle,
Brown Cody FC,
Robb Kevin P,
Sayedyahossein Samar,
Huang Kenneth,
Gros Robert,
Flynn Lauren
Publication year - 2019
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.2019.33.1_supplement.796.13
Subject(s) - adipocyte , endocrinology , medicine , adipose tissue , paracrine signalling , adipogenesis , adipokine , chemistry , lipolysis , pannexin , stromal cell , biology , intracellular , obesity , insulin resistance , receptor , biochemistry , connexin , gap junction
Pannexins (Panx) are channel‐forming glycoproteins important in paracrine signaling and cellular development. Panx1 and Panx3 are expressed in adipocytes and adipose stromal cells. We discovered that mice globally lacking Panx1 (KO) have significantly greater total fat mass and reduced lean mass compared to wild type (WT) mice under a normal diet, while Panx3 KO mice have reduced total fat mass and weigh less than WT controls. Despite having higher fat content, Panx1 KO mice on a high fat diet exhibited no differences in weight gain but showed an increase in glucose and insulin levels compared to WT. However, metabolic cage data revealed that these Panx1 KO mice display significantly increased activity levels, higher ambulatory activity, and reduced sleep duration relative to their WT littermates on a high‐fat diet. To uncover the cellular mechanism responsible for the increased fat content in the Panx1 KO, we isolated primary cultures of adipose‐derived stromal cells (ASCs) from WT and KO fat pads. In WT ASCs we observed that Panx1 protein levels increase upon induction into an adipogenic lineage. ASCs isolated from Panx1 KO mice proliferate less but demonstrate enhanced adipogenic differentiation with increased intracellular lipid accumulation, glycerol‐3‐phosphate dehydrogenase (GPDH) enzyme activity, and adipokine secretion, as compared to WT ASCs. This was consistent with the increased adipocyte size (hypertrophy) and decreased adipocyte numbers observed in subcutaneous fat of the Panx1 KO mice compared to WT. Panx3 is also expressed in adipose stromal cells and Panx3 protein levels significantly increase in differentiated adipocytes. However, the effect of the Panx3 KO seems to be the opposite of the Panx1 KO, with decreased weight under a high fat diet and lower fat mass (even under a normal chow diet). We propose that Panx1 and Panx3 may play opposing roles in adipose stromal cells during the early stages of adipogenic proliferation and differentiation, regulating fat accumulation in vivo . Support or Funding Information Funded by the Canadian Institutes of Health Research (CIHR) grants to SP and LF This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal .