C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue

Poursharifi, Pegah, Lapointe, Marc, Fisette, Alexandre, Lu, Huiling, Roy, Christian, Munkonda, Mercedes Nancy, Fairlie, David P. and Cianflone, Katherine (2014) C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue. Molecular and Cellular Endocrinology, 382 1: 325-333. doi:10.1016/j.mce.2013.10.019

Author Poursharifi, Pegah
Lapointe, Marc
Fisette, Alexandre
Lu, Huiling
Roy, Christian
Munkonda, Mercedes Nancy
Fairlie, David P.
Cianflone, Katherine
Title C5aR and C5L2 act in concert to balance immunometabolism in adipose tissue
Journal name Molecular and Cellular Endocrinology   Check publisher's open access policy
ISSN 0303-7207
Publication date 2014-01-25
Year available 2013
Sub-type Article (original research)
DOI 10.1016/j.mce.2013.10.019
Open Access Status
Volume 382
Issue 1
Start page 325
End page 333
Total pages 9
Place of publication Shannon, Co. Clare Ireland
Publisher Elsevier Ireland Ltd
Language eng
Subject 1310 Endocrinology
1312 Molecular Biology
1303 Specialist Studies in Education
Abstract Recent studies suggested that the immunometabolic receptors; C5aR and C5L2, constitutively self-associate into homo-/heterodimers and that acylation stimulating protein (ASP/C3adesArg) or C5a treatment of adipocytes increased their colocalization. The present study evaluates the C5aR contribution in adipocytes to the metabolic and immune responses elicited by ligand stimulation.The effects of C5a, ASP, and insulin on cytokine production, triglyceride synthesis (TGS), and key signaling pathways were evaluated in isolated primary adipocytes and cultured 3T3-L1 differentiated adipocytes. In addition, mRNA expression of IRS1 and PGC1α was compared in adipose tissue samples from WT vs. C5aRKO mice.Both C5a and ASP directly increased MCP-1 (238. ±. 4%; P<. 0.001. , and 377. ±. 2% vs. basal 100%; P<. 0.001, respectively) and KC (413. ±. 11%; P<. 0.001. , and 529. ±. 16%; P<. 0.001 vs. basal 100%, respectively) secretion, TGS (131. ±. 1%; P<. 0.001. , and 152. ±. 6%; P<. 0.001, vs. basal 100% respectively), and Akt/NFκB phosphorylation pathways in adipocytes. However, in C5aRKO adipocytes, C5a effects were disrupted, while stimulatory effects of ASP were mostly maintained. Addition of C5a completely blocked ASP signaling and activity in both C5aRKO and WT adipocytes as well as 3T3-L1 adipocytes. Furthermore, C5aRKO adipocytes revealed impaired insulin stimulation of cytokine production, with partial impairment of signaling and TGS stimulation, consistent with decreased IRS1 and PGC1α mRNA expression in adipose tissue.These observations indicate the importance of C5aR in adipose tissue metabolism and immunity, which may be regulated through heterodimerization with C5L2.
Keyword Acylation Stimulating Protein/C3adesArg
Adipose tissue
Complement C5a
Serpentine receptor
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID 631534
APP 1027369
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2014 Collection
Institute for Molecular Bioscience - Publications
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