C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

Abstract

As the largest endocrine organ, adipose tissue secretes many bioactive molecules that circulate in blood, collectively termed adipokines. Efforts to identify such metabolic regulators have led to the discovery of a family of secreted proteins, designated as C1q tumor necrosis factor (TNF)-related proteins (CTRPs). The CTRP proteins, adiponectin, TNF-alpha, as well as other proteins with the distinct C1q domain are collectively grouped together as the C1q/TNF superfamily. Reflecting profound biological potency, the initial characterization of these adipose tissue-derived CTRP factors finds wide-ranging effects upon metabolism, inflammation, and survival-signaling in multiple tissue types. CTRP3 (also known as CORS26, cartducin, or cartonectin) is a unique member of this adipokine family. In this review we provide a comprehensive overview of the research concerning the expression, regulation, and physiological function of CTRP3.

High molecular weight, but not total, CTRP3 levels are associated with serum triglyceride levels

“…The major significant finding of this study is that almost all circulating CTRP3 in humans is found as either the MMW or HMW oligomer. This finding supports previous speculation that the oligomer conformation of CTRP3 is important for its functional activity (Li et al, ; Peterson, ; Peterson et al, ). The secondary finding of this study is that total CTRP3 levels were almost identical between diabetic and nondiabetic populations (68.8 ± 20 vs. 70.7 ± 18 ng/ml), and there was no difference between these groups in circulating concentration of HMW or MMW CTRP3.…”

“…Further, CTRP3 has been shown to be a potent insulin sensitizer and inhibits inflammation (Peterson et al, ), indicating that CTRP3 could play a major role in metabolic diseases such as obesity, nonalcoholic fatty liver disease, and type 2 diabetes. However, the associations between total CTRP3 levels with obesity or metabolic syndrome are controversial, as circulating CTRP3 levels have been shown to be elevated, decreased, or not changed with obesity (Li, Wright, & Peterson, ). These discrepancies indicate that the role of CTRP3 in human health is more complicated than can be identified by total circulating levels.…”

“…The primary hypothesis was that, although total levels of circulating CTRP3 will be similar between people with type 2 diabetes compared with nondiabetic controls, there will be a difference between groups in the circulating oligomeric state of CTRP3. The secondary purpose of this study was to determine whether the circulating oligomeric state of CTRP3 correlates with the circulating levels of inflammatory cytokines or triglycerides as CTRP3 has been previously demonstrated to attenuate inflammation and to reduce triglyceride levels (Hofmann et al, ; Kopp, Bala, Buechler, et al, ; Kopp, Bala, Weigert, et al, ; Li et al, ; Petersen et al, ; Peterson et al, , ; Schmid, Kopp, Hanses, Karrasch, & Schaffler, ; Tan et al, ; Trogen et al, ; Yang et al, ; Yoo et al, ).…”

Progranulin serum levels and gene expression in subcutaneous vs visceral adipose tissue of severely obese patients undergoing bariatric surgery

“…26,29 CTRP-3 is an adipokine involved in adipogenesis and as a pleiotropic factor in metabolic and immunological processes which has been described to be inversely associated with BMI and metabolic syndrome. 31,32 Further being well-known for its anti-inflammatory properties, CTRP-3 thus resembles progranulin which has been described as an anti-atherosclerotic factor 33 and as an inhibitor of pro-inflammatory TNF signalling. 34,35 Similar to a potential inhibition…”

CTRP3 Regulates Endochondral Ossification and Bone Remodeling During Fracture Healing

“…C1q tumor necrosis factor (TNF)‐related proteins (CTRPs) are a family of secretory cytokines with diverse metabolic and immunomodulatory functions . First identified in C3H10T1/2 mouse embryonic stem cells undergoing transforming growth factor‐β 1 (TGFβ1)‐induced chondrogenesis and associated with early cartilage condensations in developing mice, CTRP3 (alternately known as CORS26, cartducin, or cartonectin), a paralog of adiponectin, has been implicated in a wide variety of physiological processes ranging from obesity to reproductive function . Though its association with and function in growth plate cartilages have been acknowledged since its discovery, CTRP3 was not classically believed to function in bone tissue proper .…”