{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n C1q/TNF‐related protein 3 (CTRP3), also known as cartonectin, is a multifunctional secreted cytokine that plays diverse roles in metabolism, cardiovascular homeostasis, inflammation, skeletal development, and even tumor biology. On the metabolic side, CTRP3 suppresses hepatic gluconeogenesis via Akt‐dependent pathways, thereby lowering blood glucose levels and reducing hepatic steatosis through modulation of lipid synthesis enzymes (–"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "–."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " In obesity and type 2 diabetes, circulating CTRP3 levels are frequently reduced, correlating with adverse lipid profiles and insulin resistance."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": ""}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the cardiovascular system, CTRP3 exerts cardioprotective effects by attenuating ischemia–reperfusion injury and sepsis‐induced myocardial dysfunction through mechanisms involving Sirt1 and AMPK activation, which in turn improve mitochondrial biogenesis and cellular energetics."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "5", "end_ref": "8"}]}, {"type": "t", "text": " Conversely, under conditions of chronic pressure overload, CTRP3 may promote pathological cardiac hypertrophy via activation of the TAK1–JNK and p38/CREB signaling cascades."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n CTRP3 also plays an important immunomodulatory role. It can function as an endogenous antagonist to lipopolysaccharide (LPS) and other toll‐like receptor ligands, thereby reducing the production of proinflammatory cytokines by monocytes and adipocytes."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "10"}]}, {"type": "t", "text": " This anti‐inflammatory property is further evidenced by its ability to attenuate autoimmune arthritis severity."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "11"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In the vascular compartment, CTRP3 protects endothelial cells from oxidized LDL–induced dysfunction by activating the PI3K/Akt/eNOS pathway"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "12"}]}, {"type": "t", "text": ", while also influencing vascular remodeling. For instance, CTRP3/cartducin promotes vascular smooth muscle cell proliferation via ERK1/2 and p38 MAPK signaling, a process that may contribute to neointimal formation after vascular injury."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "13"}]}, {"type": "t", "text": " Moreover, in models of arterial calcification, CTRP3 has been shown to enhance osteogenic differentiation of vascular smooth muscle cells through a reactive oxygen species–ERK/Runx2 axis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "14"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n In skeletal tissues, CTRP3 is implicated in both cartilage and bone regulation. During embryonic development, it is expressed in proliferating chondrocytes and promotes the proliferation of chondrogenic precursors, suggesting a role in cartilage formation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "15"}]}, {"type": "t", "text": " Furthermore, CTRP3 inhibits osteoclast differentiation via AMPK activation, thereby reducing bone resorption; paradoxically, in osteosarcoma cells, elevated CTRP3 can stimulate tumor cell proliferation via ERK1/2 signaling."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "16"}]}, {"type": "t", "text": " In articular cartilage, microarray analyses have revealed that C1QTNF3 is a downstream effector of HIF‐1α that exerts anti‐catabolic effects through suppression of NF‐κB activation."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "18"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Finally, emerging evidence points to neuroprotective roles for CTRP3 in ischemic brain injury, where the OIP5-AS1/miR-186-5p/CTRP3 regulatory axis modulates microglial inflammation and neuronal apoptosis."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "19"}]}, {"type": "t", "text": " In addition, aberrant expression of C1QTNF3 has been associated with prostate cancer progression, indicating its potential as a diagnostic and prognostic biomarker in oncology."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "20"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n \n "}, {"type": "p", "children": [{"type": "t", "text": "\n Collectively, these findings demonstrate that CTRP3 (C1QTNF3) functions as a pleiotropic adipokine that bridges metabolic regulation, cardioprotection, immunomodulation, vascular and skeletal homeostasis, and oncogenesis. This broad spectrum of activity makes CTRP3 a promising target for therapeutic interventions in metabolic, cardiovascular, inflammatory, and neoplastic diseases.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Jonathan M Peterson, Zhikui Wei, G William Wong "}, {"type": "b", "children": [{"type": "t", "text": "C1q/TNF-related protein-3 (CTRP3), a novel adipokine that regulates hepatic glucose output."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2010)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M110.180695"}], "href": "https://doi.org/10.1074/jbc.M110.180695"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "20952387"}], "href": "https://pubmed.ncbi.nlm.nih.gov/20952387"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Jonathan M Peterson, Marcus M Seldin, Zhikui Wei, et al. 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