Open AccessImmunomodulatory roles of CTRP 3 in endotoxemia and metabolic stress
Author(s) -
Petersen Pia S.,
Wolf Risa M.,
Lei Xia,
Peterson Jonathan M.,
Wong G. William
Publication year - 2016
Publication title -
physiological reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.918
H-Index - 39
ISSN - 2051-817X
DOI - 10.14814/phy2.12735
Subject(s) - inflammation , context (archaeology) , ccl11 , chemokine , systemic inflammation , endocrinology , insulin resistance , immunology , genetically modified mouse , medicine , cytokine , proinflammatory cytokine , adipose tissue , arthritis , tumor necrosis factor alpha , biology , transgene , insulin , ccl2 , paleontology , biochemistry , gene
C1q/ TNF ‐related protein 3 ( CTRP 3) is a secreted hormone that modulates hepatic glucose and lipid metabolism. Its circulating levels are reduced in human and rodent models of obesity, a metabolic state accompanied by chronic low‐grade inflammation. Recent studies have demonstrated an anti‐inflammatory role for recombinant CTRP 3 in attenuating LPS ‐induced systemic inflammation, and its deficiency markedly exacerbates inflammation in a mouse model of rheumatoid arthritis. We used genetic mouse models to explore the immunomodulatory function of CTRP 3 in response to acute ( LPS challenge) and chronic (high‐fat diet) inflammatory stimuli. In a sublethal dose of LPS challenge, neither CTRP 3 deficiency nor its overexpression in transgenic mice had an impact on IL ‐1 β , IL ‐6, TNF ‐ α , or MIP ‐2 induction at the serum protein or mRNA levels, contrary to previous findings based on recombinant CTRP 3 administration. In a metabolic context, we measured 71 serum cytokine levels in wild‐type and CTRP 3 transgenic mice fed a high‐fat diet or a matched control low‐fat diet. On a low‐fat diet, CTRP 3 transgenic mice had elevated circulating levels of multiple chemokines ( CCL 11, CXCL 9, CXCL 10, CCL 17, CX 3 CL 1, CCL 22 and sCD30). However, when obesity was induced with a high‐fat diet, CTRP 3 transgenic mice had lower circulating levels of IL ‐5, TNF ‐ α , sVEGF2, and sVEGFR 3, and a higher level of soluble gp130. Contingent upon the metabolic state, CTRP 3 overexpression altered chemokine levels in lean mice, and attenuated systemic inflammation in the setting of obesity and insulin resistance. These results highlight a context‐dependent immunomodulatory role for CTRP3.