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Wang et al. Adipokines in metabolism, and cardiovascular system

metabolism and this crosstalk can be realized by the (HEK) 293T cells. However, the exact modification
well-orchestrated secreted hormones. The newly mechanisms are still under investigation [16] . In addition,
discovered CTRPs family has profound significance the two isoforms of CTRP12 differ from the oligomeric
aiding better understanding of hormonal control of the structure and are distinct in the regulation of function.
energy homeostasis based upon the reports from the Full length CTRP12 preferentially stimulates the Akt
research group lead by Wong and other researchers in signaling in adipocytes, whereas the globular form
the last decade [11] . They discovered the contributions activates the mitogen-activated protein (MAP) kinase
of various CTRPs hormones to whole-body glucose signaling [16] . CTRP9, as a secreted glycoprotein, can
and lipid metabolic regulation. be multiple post-translationally modified in multiple
ways in its collagen domain. However, since the
CTRPs can dynamically modulate the response to CTRP9 globular domain is closely similar to that of
the alterations in short-term nutritional states or the adiponectin, the interaction between CTRP9 and
changes in long-term metabolic status. However, adiponectin does not need their collagen domains
the signaling pathways modulated by CTRPs are and is independent of posttranslational modification to
frequently disrupted by the metabolic perturbations of activate the downstream signaling pathways [12] . Here,
excess caloric uptake in obesity- and inflammation- we highlight the characteristics of CTRPs and their
induced disorders. Consequently, the hormone isoforms; modification of CTRPs could account for the
dysregulation leads to broad metabolic disorders functional diversity of CTRPs.
such as insulin resistance, diabetes, and obesity.
Those disruptions include the alterations of structural The circulating levels of CTRPs tend to fluctuate
organization, and post-translational modifications of according to sex, age, and alterations in the metabolic
CTRPs. states and are sensitive to different responses in
mammals. Reports have been made that CTRP6, a
For CTRPs structural organization, it has been reported protein with fundamentally different modes of action
that all CTRPs form trimers, but accumulating reports as opposed to other CTRPs characterized to date, is a
reveal that CTRP3, CTRP5, CTRP9, CTRP6, CTRP8, negative physiological regulator of glucose metabolism
CTRP10, CTRP11, CTRP12, CTRP13 and CTRP15 can in adipocytes, skeletal muscle and liver to control the
further assemble into multimeric complexes mediated systemic energy balance. Expression of CTRP6 is
by the N-terminal Cysteine residues or with the aid of upregulated in leptin deficient animals and increases
oxidoreductase. Adiponectin, as an insulin sensitizer, in diabetic animals . However, other researchers
[8]
assembles with CTRP9 to form heterotrimers [12] , by have reported that CTRP6 induces fatty acid oxidation
which CTRP9 and adiponectin share the same receptor in myocytes via AMPK activation [17] . These studies
to exert their cardiovascular protective function [13] . suggest that the newly discovered CTRPs still need
In addition to forming the homo-oligomers, CTRP6/ to be investigated further in depth to understand
CTRP1, CTRP7/CTRP2, and CTRP2/adiponectin form their diverse functions. In addition, other CTRPs
heterotrimers generating functionally distinct ligands functional analysis reveals various roles of CTRPs.
to provide new framework for the action of this family CTRP2 exerts fatty acid oxidation and glycogen
of secreted glycoproteins in normal and diseases deposition in myotubes [18] . CTRP1 transcript levels are
[11]
states . CTRP9 has 2 isoforms 9A and 9B, whereas augmented by rosiglitazone in mice, which enhance
CTRP9B requires physical interaction with CTRP9A the insulin sensitizing action on the skeletal muscle via
and adiponectin for completing its function [14] . CTRP8 activation of the AMPK and Akt pathways [19] . CTRP3
in addition to forming homotrimers, forms heteromeric can be a secreted plasma hormone and regulates
complexes with CTRP1, CTRP9 and CTRP10. It hepatic gluconeogenesis. The metabolic regulatory
effectively activates GPCR relaxin/insulin like family action of CTRP3 is the downregulation of its plasma
peptide receptor (RXFP1 receptor) to enhance the concentration which indicates that CTRP3 has a
motility of the glioblastoma through regulating the significant role in regulation of the lipid metabolism
activity of cathepsin B [15] . although the exact mechanism has not yet been
established. However, CTRP3 deficiency reduces the
CTRPs, as secreted hormones are subjected to liver size which indicates that its target organ appears
multiple functionally relevant post-translational to be the liver. Additionally, reduced circulating level
modifications at their highly conserved residues. of CTRP3 alters the inflammatory responses in the
CTRP12 is glycosylated on the 39th Asparagine obese animals and the short-term daily administration
amino acid and the 85th Cysteine modified with of CTRP3 in diet-induced obese mice has been
oligosaccharides which mediates the assembly of sufficient to improve the fatty liver phenotype, as
oligomeric structure in human embryonic kidney evidenced by the suppressed triglyceride content and

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