Immunomodulatory roles of CTRP3 in endotoxemia and metabolic stress

Pia S. Petersen, Risa Wolf, Xia Lei, Jonathan M. Peterson, Guang William Wong

Research output: Contribution to journalArticle

Abstract

C1q/TNF-related protein 3 (CTRP3) 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 CTRP3 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 CTRP3 in response to acute (LPS challenge) and chronic (high-fat diet) inflammatory stimuli. In a sublethal dose of LPS challenge, neither CTRP3 deficiency nor its overexpression in transgenic mice had an impact on IL-1β, IL-6, TNF-α, or MIP-2 induction at the serum protein or mRNA levels, contrary to previous findings based on recombinant CTRP3 administration. In a metabolic context, we measured 71 serum cytokine levels in wild-type and CTRP3 transgenic mice fed a high-fat diet or a matched control low-fat diet. On a low-fat diet, CTRP3 transgenic mice had elevated circulating levels of multiple chemokines (CCL11, CXCL9, CXCL10, CCL17, CX3CL1, CCL22 and sCD30). However, when obesity was induced with a high-fat diet, CTRP3 transgenic mice had lower circulating levels of IL-5, TNF-α, sVEGF2, and sVEGFR3, and a higher level of soluble gp130. Contingent upon the metabolic state, CTRP3 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.

Original languageEnglish (US)
Pages (from-to)1-13
Number of pages13
JournalPhysiological Reports
Volume4
Issue number5
DOIs
StatePublished - Mar 1 2016

Fingerprint

Physiological Stress
Endotoxemia
Transgenic Mice
Proteins
High Fat Diet
Inflammation
Fat-Restricted Diet
Obesity
Chemokine CXCL9
Chemokine CCL11
Cytokine Receptor gp130
Protein Deficiency
Genetic Models
Interleukin-5
Interleukin-1
Lipid Metabolism
Chemokines
Insulin Resistance
Blood Proteins
Rodentia

Keywords

  • CTRP3
  • Cytokines
  • Inflammation
  • LPS
  • Obesity

ASJC Scopus subject areas

  • Physiology (medical)
  • Physiology

Cite this

Immunomodulatory roles of CTRP3 in endotoxemia and metabolic stress. / Petersen, Pia S.; Wolf, Risa; Lei, Xia; Peterson, Jonathan M.; Wong, Guang William.

In: Physiological Reports, Vol. 4, No. 5, 01.03.2016, p. 1-13.

Research output: Contribution to journalArticle

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