{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nCTRP4 (also referred to as FAM74A6 in some databases) is a secreted glycoprotein that plays a pivotal role in the central regulation of energy homeostasis. It is expressed early in brain development by neurons and secreted into the circulation, where its levels are sensitive to nutritional cues. Central administration or overexpression of CTRP4 in rodent models leads to reduced food intake, an effect that is associated with a decrease in hunger‐promoting neuropeptides (e.g., Npy and Agrp) and an increase in anorexigenic signals (i.e., POMC) via the activation of STAT3 signaling and suppression of inhibitory molecules such as SOCS3. These findings suggest that CTRP4 constitutes a nutrient-responsive modulator that links hypothalamic inflammation to the regulation of feeding behavior."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n\nIn addition to its actions on energy balance, CTRP4 exerts significant anti‐inflammatory effects. In models of sepsis, exogenous administration of CTRP4 or cellular sources of CTRP4 in macrophages dampened the TLR4-driven inflammatory cascade and cytokine storm, leading to improved survival and reduced organ damage. Similarly, in colitis-associated colorectal cancer models, transgenic overexpression of CTRP4 resulted in markedly attenuated colonic inflammation, reduced interleukin-6 levels, decreased activation of ERK, STAT3, and Akt signaling pathways, and ultimately a lower tumor burden with more superficial, lower-grade lesions."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n\nEmerging evidence also indicates that CTRP4 contributes to bone metabolism by promoting osteoblast differentiation and mineralization. Studies in osteoblast cultures and in vivo bone loss models demonstrate that reduced expression of CTRP4 correlates with lower levels of key osteogenic markers such as alkaline phosphatase and osteocalcin (Bglap), activities that are essential for proper bone formation. This osteoanabolic action positions CTRP4 as a potential target for therapeutic intervention in metabolic bone diseases."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "6"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Mardi S Byerly, Pia S Petersen, Santosh Ramamurthy, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C1q/TNF-related protein 4 (CTRP4) is a unique secreted protein with two tandem C1q domains that functions in the hypothalamus to modulate food intake and body weight."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2014)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M113.506956"}], "href": "https://doi.org/10.1074/jbc.M113.506956"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24366864"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24366864"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Yuejie Li, Liu Ye, Gongwei Jia, et al. 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"}, {"type": "b", "children": [{"type": "t", "text": "Expression of the novel adipokine C1qTNF-related protein 4 (CTRP4) suppresses colitis and colitis-associated colorectal cancer in mice."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cell Mol Immunol (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/cmi.2016.16"}], "href": "https://doi.org/10.1038/cmi.2016.16"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27086950"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27086950"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lulu Cao, Weifeng Tan, Wei Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CTRP4 acts as an anti-inflammatory factor in macrophages and protects against endotoxic shock."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Eur J Immunol (2021)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/eji.202048617"}], "href": "https://doi.org/10.1002/eji.202048617"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "33080044"}], "href": "https://pubmed.ncbi.nlm.nih.gov/33080044"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Qi Li, Jieheng Wu, Wenjin Xi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Ctrp4, a new adipokine, promotes the differentiation of osteoblasts."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Biochem Biophys Res Commun (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.bbrc.2019.03.053"}], "href": "https://doi.org/10.1016/j.bbrc.2019.03.053"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30885436"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30885436"}]}]}]}