A new effector of lipid metabolism: Complement factor properdin

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• 作者：Danny Gauvreau^a ; ^b ; Christian Roy^a ; ^b ; Fun-Qun Tom^a ; ^b ; HuiLing Lu^a ; ^b ; Pierre Miegueu^a ; ^b ; Denis Richard^a ; ^b ; Wen-Chao Song^c ; Cordula Stover^d ; Katherine Cianflone^a ; ^b ; ^{katherine.cianflone@criucpq.ulaval.ca}
• 关键词：C3adesArg/ASP ; acylation stimulating protein ; TG ; triglyceride ; NEFA ; non-esterified fatty acid ; PKO ; properdin knock-out ; RQ ; respiratory quotient ; DEXA ; dual-energy X-ray absorptiometry ; CD36/FAT ; fatty acid translocase ; TSP-1 ; thrombospondin-1 ; FIAD ; f
• 刊名：Molecular Immunology
• 出版年：2012
• 期刊代码：112_01615890
• 类别：bio
• 出版时间：May, 2012
• 卷：51
• 期：1
• 页码：73-81
• 文件大小：1008 K

摘要

Background

The complement system is well known for its role in innate immunity via the classical, the alternative and the lectin pathways, although recent investigations suggest expanding roles in adipose tissue. Properdin stabilizes C3 convertase following alternative complement activation. Properdin is also present in adipose tissue, localized to adipocyte membranes.

Aim

We evaluated the potential role of properdin in energy metabolism using properdin deficient (PKO) mice and cell based assays.

Results

PKO mice have a diet-dependent increase in weight gain compared to wild-type (WT) littermates on a high fat diet (P&#xA0;<&#xA0;0.05), directly related to 51%increase in relative fat mass (PKO: 35.8&#xA0;卤&#xA0;2.2%body fat vs. WT: 23.6&#xA0;卤&#xA0;2.2%, P&#xA0;<&#xA0;0.01). PKO mice have decreased energy expenditure (P&#xA0;<&#xA0;0.01), and altered postprandial lipid clearance (P&#xA0;<&#xA0;0.01). However glucose metabolism was unchanged after a glucose tolerance test vs. WT mice. In murine 3T3-L1 adipocytes, addition of properdin had no effect on C3 or ASP production but almost completely inhibited the insulin-mediated stimulation of fatty acid uptake and incorporation into TG. Properdin had no effect on basal or insulin-stimulated glucose transport in either 3T3-L1 adipocytes or L6 rat skeletal muscle cells.

Conclusion

Thus properdin may be added to the growing list of complement proteins (C3, adipsin, factor B, ASP (C3adesArg), factor H, C1q and C3aR) which influence lipid metabolism, energy storage and insulin resistance, and further support the hypothesis of a dual role of complement in adipose tissue.