C1QTNF3

C1QTNF3 Full Name

C1q and tumor necrosis factor related protein 3

C1QTNF3 Introduction

C1QTNF3, also known as C1q/TNF-related protein 3 (CTRP3), is an adipokine that has garnered increasing research attention in recent years. As a member of the C1q/TNF superfamily, it is primarily highly expressed in adipose tissue and functions as a secreted protein, playing important regulatory roles in metabolic homeostasis and immune responses. Its structure consists of an N-terminal signal peptide, a collagen-like domain, and a C-terminal C1q-like globular domain—a modular architecture that enables diverse ligand recognition capabilities.

Figure 1. Structural overview of CTRP3. (Source: Li Y, et al. 2017)

C1QTNF3 exhibits dual significant functions in anti-inflammation and metabolic regulation. In metabolism, it activates the PI3K/Akt signaling pathway and suppresses the expression of key hepatic gluconeogenic genes (such as PEPCK and G6Pase), thereby reducing hepatic glucose output and improving systemic insulin sensitivity. Additionally, C1QTNF3 directly inhibits the differentiation of preadipocytes and reduces lipid accumulation, playing a significant role in adipose tissue remodeling. In terms of inflammatory regulation, C1QTNF3 acts as an endogenous LPS antagonist, blocking lipopolysaccharide-induced activation of the TLR4 signaling pathway. It downregulates the secretion of pro-inflammatory cytokines such as TNF-α and IL-6 in macrophages and shows a negative correlation with IL-6 and IL-8 expression, demonstrating broad-spectrum anti-inflammatory properties. This anti-inflammatory effect is also reflected in macrophage polarization, where C1QTNF3 promotes the formation of M2 anti-inflammatory macrophages while suppressing the M1 pro-inflammatory phenotype.

Dysregulation of C1QTNF3 is closely associated with various metabolic and inflammatory diseases. Serum levels of C1QTNF3 are significantly reduced in patients with type 2 diabetes and obesity, and its expression negatively correlates with insulin resistance indices, suggesting its potential role as a protective factor in metabolic syndrome. Animal model studies have shown that C1QTNF3 knockout mice exhibit aggravated chronic adipose tissue inflammation, worsened hepatic steatosis, and impaired glucose tolerance, while its overexpression effectively alleviates these symptoms. Notably, in acute inflammatory conditions such as viral infections (e.g., African swine fever virus infection), downregulation of C1QTNF3 further amplifies the inflammatory response, creating a vicious cycle.

Alternate Names for C1QTNF3

C1QTNF3; C1q and tumor necrosis factor related protein 3; CORS; CORCS; CTRP3; CORS26; C1ATNF3; CORS-26; complement C1q tumor necrosis factor-related protein 3; cartonectin

• 1. Li Y, et al. C1q/TNF-Related Protein 3 (CTRP3) Function and Regulation. Compr Physiol. 2017 Jun 18;7(3):863-878.
  2. Yaribeygi H, et al. C1q/TNF-related protein-3 and glucose homeostasis. Diabetes Metab Syndr. 2019 May-Jun;13(3):1923-1927.