{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n C1q/TNF‐related protein 12 (CTRP12), also known as adipolin or Fam132a, is an adipose tissue–derived hormone with potent insulin‐sensitizing and anti‐inflammatory actions. It improves glucose metabolism by enhancing insulin signaling in both liver and adipose tissue through insulin‐dependent as well as independent mechanisms, while also directly modulating lipid metabolism by suppressing triglyceride synthesis and very‐low‐density lipoprotein export from hepatocytes (​."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n CTRP12 exists in at least two isoforms – a full‐length form that predominantly activates the Akt signaling cascade, and a cleaved globular form that favors MAP kinase pathways. This cleavage‐dependent divergence in signaling is regulated by posttranslational modifications such as N‐glycosylation and furin/PCSK3‐mediated processing, thereby ensuring target‐specific activity (​."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "4"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n Expression and circulating levels of CTRP12 are reduced under conditions of obesity, type 2 diabetes, and coronary artery disease. Pharmacological agents like rosiglitazone and metformin have been shown to elevate its production in adipocytes, while transcriptional control by factors such as KLF3 links its expression to adipogenesis and energy homeostasis (​."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "6", "end_ref": "9"}]}, {"type": "t", "text": "\n "}]}, {"type": "t", "text": "\n "}, {"type": "p", "children": [{"type": "t", "text": "\n In summary, CTRP12 serves as a key metabolic regulator that not only enhances insulin sensitivity and improves glucose and lipid metabolism but also mitigates inflammatory responses. These combined actions underscore its potential both as a diagnostic biomarker and as a therapeutic target for metabolic disorders and cardiovascular disease.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Zhikui Wei, Jonathan M Peterson, Xia Lei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "C1q/TNF-related protein-12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.303651"}], "href": "https://doi.org/10.1074/jbc.M111.303651"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22275362"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22275362"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Takashi Enomoto, Koji Ohashi, Rei Shibata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Adipolin/C1qdc2/CTRP12 protein functions as an adipokine that improves glucose metabolism."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2011)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M111.277319"}], "href": "https://doi.org/10.1074/jbc.M111.277319"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "21849507"}], "href": "https://pubmed.ncbi.nlm.nih.gov/21849507"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Stefanie Y Tan, Hannah C Little, Dylan C Sarver, et al. "}, {"type": "b", "children": [{"type": "t", "text": "CTRP12 inhibits triglyceride synthesis and export in hepatocytes by suppressing HNF-4α and DGAT2 expression."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "FEBS Lett (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1002/1873-3468.13895"}], "href": "https://doi.org/10.1002/1873-3468.13895"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32749667"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32749667"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Zhikui Wei, Xia Lei, Marcus M Seldin, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Endopeptidase cleavage generates a functionally distinct isoform of C1q/tumor necrosis factor-related protein-12 (CTRP12) with an altered oligomeric state and signaling specificity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Biol Chem (2012)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1074/jbc.M112.365965"}], "href": "https://doi.org/10.1074/jbc.M112.365965"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "22942287"}], "href": "https://pubmed.ncbi.nlm.nih.gov/22942287"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Takashi Enomoto, Koji Ohashi, Rei Shibata, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Transcriptional regulation of an insulin-sensitizing adipokine adipolin/CTRP12 in adipocytes by Krüppel-like factor 15."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0083183"}], "href": "https://doi.org/10.1371/journal.pone.0083183"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "24358263"}], "href": "https://pubmed.ncbi.nlm.nih.gov/24358263"}]}, {"type": "r", "ref": 6, "children": [{"type": "t", "text": "Kim S Bell-Anderson, Alister P Funnell, Helen Williams, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Loss of Krüppel-like factor 3 (KLF3/BKLF) leads to upregulation of the insulin-sensitizing factor adipolin (FAM132A/CTRP12/C1qdc2)."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Diabetes (2013)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.2337/db12-1745"}], "href": "https://doi.org/10.2337/db12-1745"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "23633521"}], "href": "https://pubmed.ncbi.nlm.nih.gov/23633521"}]}, {"type": "r", "ref": 7, "children": [{"type": "t", "text": "Bo Bai, Bo Ban, Zunjing Liu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Circulating C1q complement/TNF-related protein (CTRP) 1, CTRP9, CTRP12 and CTRP13 concentrations in Type 2 diabetes mellitus: In vivo regulation by glucose."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2017)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0172271"}], "href": "https://doi.org/10.1371/journal.pone.0172271"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "28207876"}], "href": "https://pubmed.ncbi.nlm.nih.gov/28207876"}]}, {"type": "r", "ref": 8, "children": [{"type": "t", "text": "Reza Fadaei, Nariman Moradi, Tooba Kazemi, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Decreased serum levels of CTRP12/adipolin in patients with coronary artery disease in relation to inflammatory cytokines and insulin resistance."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Cytokine (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.cyto.2018.09.019"}], "href": "https://doi.org/10.1016/j.cyto.2018.09.019"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30337217"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30337217"}]}, {"type": "r", "ref": 9, "children": [{"type": "t", "text": "Mehrnoosh Shanaki, Nariman Moradi, Reza Fadaei, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Lower circulating levels of CTRP12 and CTRP13 in polycystic ovarian syndrome: Irrespective of obesity."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "PLoS One (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1371/journal.pone.0208059"}], "href": "https://doi.org/10.1371/journal.pone.0208059"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30540803"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30540803"}]}]}]}