C1q/Tumor Necrosis Factor-Related Protein 9: Basics and Therapeutic Potentials

Abstract

C1q/tumor necrosis factor-related protein 9 (CTRP9) is a newly discovered adipokine that is the closest paralog of adiponectin. Proteolytic cleavage of CTRP9 leads to the release of the globular domain (gCTRP9), which serves as the major circulating subtype. After binding with adiponectin receptor 1 (AdipoR1) and N-cadherin, CTRP9 activates various signaling pathways to regulate glucose and lipid metabolism, vasodilation and cell differentiation. Throughout human development and adult life, CTRP9 controls many biological phenomena. simultaneously, abnormal gene or protein expression of CTRP9 is accompanied by a wide range of human pathological phenomena. In this review, we briefly introduce CTRP9 and its associated signaling pathways and physiological functions, which may be helpful in the understanding of the occurrence of diseases. Moreover, we summarize the broader research prospects of CTRP9 and advances in therapeutic intervention. In recent years, CTRP9 has attracted extensive attention due to its role in the pathogenesis of various diseases, providing further avenues for its exploitation as a potential biomarker or therapeutic target.

Putative therapeutic impacts of cardiac CTRP9 in ischaemia/reperfusion injury

“…As mentioned earlier, CTRP9 has the potential to be an option for improving glucose‐related metabolic syndrome 78 . Previous data showed that serum levels of leptin and adiponectin were significantly lower in patients with type 2 diabetes, 79 which would be predictive of circulating CTRP9 54,79,80 .…”

“…As mentioned earlier, CTRP9 has the potential to be an option for improving glucose‐related metabolic syndrome. 78 Previous data showed that serum levels of leptin and adiponectin were significantly lower in patients with type 2 diabetes, 79 which would be predictive of circulating CTRP9. 54 , 79 , 80 It has also been indicated that serum levels of CTRP9 were remarkably correlated with systolic pressure and C‐reactive protein levels in diabetic subjects.…”

CTRP9 Promotes Brown Adipose Tissue Lipolysis in Mice Fed a High-Fat Diet

“…CTRP9 was reported to regulate the pathological processes associated with obesity [21], lipid metabolism [22], cardiovascular disease [23], myocardial ischemia [24], apoptosis [25], and pulmonary artery pressure [26]. Thus, these critical roles of CTRP9 in pathological and physiological conditions have piqued the interest of the scientific community [27]. However, the effect of CTRP9 on brown adipocyte formation and lipid metabolism has not been elucidated.…”

Knockout of C1q/tumor necrosis factor-related protein-9 aggravates cardiac fibrosis in diabetic mice by regulating YAP-mediated autophagy

“…C1q/tumor necrosis factor-related protein 9 (CTRP9) is a recently discovered adipokine within the CTRP superfamily, playing a pivotal role in regulating glycolipid metabolism and providing cardioprotection ( Zhao et al, 2018 ; Guan et al, 2022 ). Clinical investigations have unveiled a correlation between lower CTRP9 levels and metabolic syndrome, and insulin resistance in diabetic individuals ( Hwang et al, 2014 ; Jia et al, 2017 ; Moradi et al, 2018 ).…”