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Critical role for cytosolic group IVA phospholipase A2 in early adipocyte differentiation and obesity

AuthorsPeña, Lucía ; Meana, Clara ; Astudillo, Alma M. ; Lordén, Gema; Valdearcos, Martín ; Sato, Hiroyasu; Murakami, Makoto; Balsinde, Jesús ; Balboa, María A.
KeywordsPhospholipase A2
Arachidonic acid
Issue Date2016
CitationBiochimica et Biophysica Acta - Molecular and Cell Biology of Lipids 1861(9A): 1083-1095 (2016)
AbstractAdipogenesis is the process of differentiation of immature mesenchymal stem cells into adipocytes. Elucidation of the mechanisms that regulate adipocyte differentiation is key for the development of novel therapies for the control of obesity and related comorbidities. Cytosolic group IVA phospholipase A (cPLAα) is the pivotal enzyme in receptor-mediated arachidonic acid (AA) mobilization and attendant eicosanoid production. Using primary multipotent cells and cell lines predetermined to become adipocytes, we show here that cPLAα displays a proadipogenic function that occurs very early in the adipogenic process. Interestingly, cPLAα levels decrease during adipogenesis, but cPLAα-deficient preadipocytes exhibit a reduced capacity to differentiate into adipocytes, which affects early and terminal adipogenic transcription factors. Additionally, the absence of the phospholipase alters proliferation and cell-cycle progression that takes place during adipogenesis. Preconditioning of preadipocytes with AA increases the adipogenic capacity of these cells. Moreover, animals deficient in cPLAα show resistance to obesity when fed a high fat diet that parallels changes in the expression of adipogenic transcription factors of the adipose tissue. Collectively, these results show that preadipocyte cPLAα activation is a hitherto unrecognized factor for adipogenesis in vitro and in vivo.
Publisher version (URL)https://doi.org/10.1016/j.bbalip.2016.06.004
Identifiersdoi: 10.1016/j.bbalip.2016.06.004
issn: 1388-1981
Appears in Collections:(IBGM) Artículos
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