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Ghandour, R.A.* ; Giroud, M.* ; Vegiopoulos, A.* ; Herzig, S. ; Ailhaud, G.* ; Amri, E.Z.* ; Pisani, D.F.*

IP-receptor and PPARs trigger the conversion of human white to brite adipocyte induced by carbaprostacyclin.

Biochim. Biophys. Acta-Mol. Cell Biol. Lipids 1861, 285-293 (2016)
Postprint DOI PMC
Open Access Green
Brite adipocytes recently discovered in humans are of considerable importance in energy expenditure by converting energy excess into heat. This property could be useful in the treatment of obesity, and nutritional aspects are relevant to this important issue. Using hMADS cells as a human cell model which undergoes a white to a brite adipocyte conversion, we had shown previously that arachidonic acid, the major metabolite of the essential nutrient Ω6-linoleic acid, plays a major role in this process. Its metabolites PGE2 and PGF2 alpha inhibit this process via a calcium-dependent pathway, whereas in contrast carbaprostacyclin (cPGI2), a stable analog of prostacyclin, activates white to brite adipocyte conversion. Herein, we show that cPGI2 generates via its cognate cell-surface receptor IP-R, a cyclic AMP-signaling pathway involving PKA activity which in turn induces the expression of UCP1. In addition, cPGI2 activates the pathway of nuclear receptors of the PPAR family, i.e. PPARα and PPARγ, which act separately from IP-R to up-regulate the expression of key genes involved in the function of brite adipocytes. Thus dual pathways are playing in concert for the occurrence of a browning process of human white adipocytes. These results make prostacyclin analogs as a new class of interesting molecules to treat obesity and associated diseases.
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Publication type Article: Journal article
Document type Scientific Article
Corresponding Author
Keywords Brown Adipocyte ; Obesity ; Prostacyclin ; Ucp1 ; Camp ; Cpgi2; Brown Adipose-tissue; Polyunsaturated Fatty-acids; Stable Prostacyclin Analog; Adult Humans; Arachidonic-acid; Beraprost Sodium; Cells; Pharmacokinetics; Activation; Pathway
ISSN (print) / ISBN 1388-1981
Journal Biochimica et Biophysica Acta Molecular and Cell Biology of Lipids
Quellenangaben Volume: 1861, Issue: 4, Pages: 285-293 Article Number: , Supplement: ,
Publisher Elsevier
Publishing Place Amsterdam
Non-patent literature Publications
Reviewing status Peer reviewed
Institute(s) Institute of Diabetes and Cancer (IDC)