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Wang et al. Adipokines in metabolism, and cardiovascular system

expression of the triglyceride synthesis genes [1,20] . can serve as potential novel biomarkers for the
Hence, CTRP3 shows potent action on the regulation prediction and early diagnosis of type-2 diabetes, and
of metabolism. Loss of CTRP5 improves the insulin furthermore, they represent a new treatment strategy.
action states and hepatic steatosis. Deletion of CTRP7 CTRP3 can be a better predictor for coronary artery
attenuates the obesity-linked glucose intolerance disease than other CTRPs.
of cytokine expression and circulating levels of
[8]
cytokine . Overexpression of CTRP9 modestly CTRPS AND INFLAMMATION
downregulates the serum glucose and insulin levels.
CTRP9 and CTRP15 are considered as cardiokine Metabolic syndrome such as obesity is associated with
(the heart-derived proteins are termed cardiokines) the chronic low-level inflammation, and therefore the
due to their high profile in the cardiac tissue and metabolic regulators connecting obesity and diabetes
for their protective and preventive actions against to the inflammatory response have attracted much
cardiovascular injury. Although the CTRP9’s functional attention. In addition, it has been gradually recognized
receptor has not been thoroughly investigated, that the imbalance of anti-inflammatory adipokines
cadherin family appears to be a potential candidate [21] . and pro-inflammatory factors leads to the progression
Loss of CTRP12 affects the glucose and lipid of obesity-related diseases. Disrupted anti-
metabolism in the obese and insulin-resistant mouse inflammatory adipokines participate in the systemic
models [22] . CTRP13 regulates the metabolism through or local inflammatory reactions contributing to the
AMPK activation and decrease of fatty acid-induced initiation and development of metabolic dysfunction
JNK signaling [23] . CTRP15 links skeletal muscle and and cardiovascular events. In this regard, to define
liver to systemic lipid homeostasis [21] . We summarize the imbalance of anti-inflammatory adipokines
current understanding of CTRPs metabolic functions (CTRPs) and proinflammatory factors (risks factor)
and provide insight into the dynamic regulatory role of would be valuable in studying the obesity-associated
CTRP on metabolic balance. Although much has been complications. Hence, this section will emphasize the
acknowledged since CTRPs were initially defined, possible associations of CTRPs with cardiovascular
many more questions remain to be addressed. inflammation.

Of all the CTRPs, CTRP1, CTRP3, CTRP9, CTRP12, CTRPs as a priming potential biomarker for predicting
CTRP13 have been reported to exhibit positive the dysfunctional metabolic status and therapeutic
metabolic regulation and cardiovascular effects in target has drawn much attention. Thus, their
animal models. However, in human studies, circulating capability of regulation of metabolism has been widely
levels of CTRP1 are elevated, while CTRP12 investigated and documented. However, the association
displayed a decrease in type-2 diabetes patients. between CTRPs and inflammation, insulin resistance/
Thus, circulating CTRP1 and CTRP12 can serve as obesity-linked inflammation, and pro-inflammatory
potential novel biomarkers for the early diagnosis of cytokines needs to be thoroughly investigated even
type-2 diabetes in humans [24,25] . The measurement of although these relationships between those disorders
circulating CTRPs in serum is through commercially besides CTRPs have been well documented.
available ELISA kits provide by Aviscera company
(Santa Clara, USA). CTRP3, in recent human studies, CTRPs protect against the complications of obesity
was increased in subjects with the cardio-metabolic such as cardiovascular diseases (CVDs) via their anti-
syndrome and is associated with various cardio- inflammatory properties. Obesity is characterized by
metabolic risk factors including the triglycerides, high- chronic inflammation leading to the obesity-related
density lipoprotein-cholesterol, waist-to-hip ratio, and diseases including hypertension, atherosclerosis,
eGFR, which indicate the decreased CTRP3 levels and diabetes, while CTRPs as secretory proteins
that may serve as a predictor of coronary artery circulating in the organism can easily reach the site of
disease, while CTRP13 cannot serve as a predictor infection to exert its anti-inflammatory characteristics.
candidate since there is evidence that CTRP13 mRNA
expression is increased in the setting of obesity [26,27] . Recent studies have shown new insights into CTRP6.
This contradiction may be attributed to different nature For example, upregulation of CTRP6 in the leptin
of human and rodent studies. knock-out mice and under diabetic conditions shows
[5]
distinct roles of CTRP6 in modulating inflammation .
Collectively, based upon properties of the known In contrast to other CTRPs, CTRP6 expression is
and characterized CTRPS, a strategy designed for obviously elevated in adipose tissue and vascular
screening the biomarkers to predict the metabolic- cells in obese, diabetic patients and mouse models.
related disease reveals that CTRP1 and CTRP12 Overexpression of CTRP6 not only impairs glucose

206 Vessel Plus ¦ Volume 1 ¦ December 28, 2017