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Wang et al. Adipokines in metabolism, and cardiovascular system

A features and therapeutic roles in the metabolic energy
Collagen (Gly-X-Y) Signal peptide balance regulation, inflammatory responses and in
obesity-associated disorders.

WHAT ARE CTRPS?

Globular C1q domain Variable region CTRPs, first identified by the Harvey Lodish laboratory,
are considered a new family of secreted proteins from
various organs. These 15 secreted proteins (CTRP1
B Trimer to CTRP15) share common structural and functional
characteristics with adiponectin: a N-terminal
signal peptide, a short variable region, a collagen
domain containing collagen triples (Gly-X-Y), and a
C-terminal globular complement factor C1q domain
[Figure 1] [1,2] . CTRPs display distinct biological and
signaling properties by occurring in the circulation as
trimers and assembling with their basic structural unit
C into hexameric and high molecular weight oligomeric
Oligomer
complexes [Figure 1]. Most CTRPs are expressed by
adipose tissue and circulate in plasma. Their plasma
levels vary with the genetic background, age, gender,
and metabolic states. In terms of CTRPs sexually
dimorphic patterns, female mice express higher levels
of CTRP13, CTRP11, CTRP9, CTRP5, and CTRP3
compared to male animals/humans [1-5] . The exact
mechanism for these differences is still unclear.

CTRPs are expressed and distributed in a variety
of ways that may determine their diverse biological
functions [Table 1]. To date, metabolic functions have
been established for CTRP1, CTRP2, CTRP3, CTRP5,
[2]
Figure 1: Structural organization of the CTRPs. A: domain structure and CTRP9 . Although the functional receptors for
of CTRP monomeric protein; B: homotrimeric CTRP protein structure. CTRPs have not yet been recognized, vascular, liver,
C: CTRP trimeric proteins form higher-order three-dimensional
structures. CTRPs: C1q/tumor necrosis factor-related proteins muscle, heart and adipose tissue are the likely targets
of CTRPs. They share similar structure and function
with adiponectin , including the regulation of balance
[6]
cardiovascular disease, the inflammatory process). of body energy metabolism through enhancing
insulin sensitivity in the liver and muscle, exhibition
Adiponectin, discovered as the first member of the of anti-inflammatory responses, and protection of the
C1q/tumor necrosis factor-related proteins (CTRPs) cardiovascular system (CVS). Thus, the CTRP family
family, has been broadly investigated because of its may have parallel implications for energy homeostasis
metabolic regulatory and cardiovascular protective and provides new pharmacological targets in the
effects. To date, additional CTRP family members, obesity-related diseases and type 2 diabetes.
a newly discovered novel family of adipokines, have Meanwhile, they consist of many family members
been identified that may play a role in metabolism distributed in various organs, hence they have the
and cardiovascular system path-physiological potential to serve as biomarkers in the obesity-related
regulation. Hence, in future, the studies on these diseases and may serve as detectable parameters for
novel adipokines will provide new understandings into early prognosis and diagnosis.
the physiological/pathological mechanisms including
the communication of different organs based on
energy homeostasis, homeostasis of the internal CTRPS IN CIRCULATION
environment, and prevention of inflammation.
Endogenous CTRPs can be detected in the blood by
The current review focuses on the main roles of enzyme-linked immunosorbent assay (ELISA), even
CTRPs in the context of pathophysiology with although they circulate at 1-2 orders of magnitude less
particular attention to their potential biomarker than adiponectin. The distribution of CTRPs levels
Vessel Plus ¦ Volume 1 ¦ December 28, 2017 203