Comprehensive Physiology Wiley Online Library

C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation

Full Article on Wiley Online Library


As the largest endocrine organ, adipose tissue secretes many bioactive molecules that circulate in blood, collectively termed adipokines. Efforts to identify such metabolic regulators have led to the discovery of a family of secreted proteins, designated as C1q tumor necrosis factor (TNF)‐related proteins (CTRPs). The CTRP proteins, adiponectin, TNF‐alpha, as well as other proteins with the distinct C1q domain are collectively grouped together as the C1q/TNF superfamily. Reflecting profound biological potency, the initial characterization of these adipose tissue‐derived CTRP factors finds wide‐ranging effects upon metabolism, inflammation, and survival‐signaling in multiple tissue types. CTRP3 (also known as CORS26, cartducin, or cartonectin) is a unique member of this adipokine family. In this review we provide a comprehensive overview of the research concerning the expression, regulation, and physiological function of CTRP3. © 2017 American Physiological Society. Compr Physiol 7:863‐878, 2017.

Comprehensive Physiology offers downloadable PowerPoint presentations of figures for non-profit, educational use, provided the content is not modified and full credit is given to the author and publication.

Download a PowerPoint presentation of all images

Figure 1. Figure 1. Structural overview of CTRP3. The human CTRP3A gene is 25.3 kb in size, consists of six exons and five introns, and is located on chromosome 5p13. Exons 1, 2, 3, 4, 5, and 6 of the CTRP3A gene are 171, 112, 155, 130, 100, and 2885 bp in size, respectively. The size of each intron is also indicated. Exon 1B (gray square) contains a 219‐nucleotide sequence found in CTRP3B cDNA, coding for an extra 73 amino acid residues. A potential N‐linked glycosylation site is circled. The consensus splice donors are shown in italic type. This figure was originally published in The Journal of Biological Chemistry (51) and image reproduced according to the copyright policy of the ASBMB. © the American Society for Biochemistry and Molecular Biology.

Figure 1. Structural overview of CTRP3. The human CTRP3A gene is 25.3 kb in size, consists of six exons and five introns, and is located on chromosome 5p13. Exons 1, 2, 3, 4, 5, and 6 of the CTRP3A gene are 171, 112, 155, 130, 100, and 2885 bp in size, respectively. The size of each intron is also indicated. Exon 1B (gray square) contains a 219‐nucleotide sequence found in CTRP3B cDNA, coding for an extra 73 amino acid residues. A potential N‐linked glycosylation site is circled. The consensus splice donors are shown in italic type. This figure was originally published in The Journal of Biological Chemistry (51) and image reproduced according to the copyright policy of the ASBMB. © the American Society for Biochemistry and Molecular Biology.
 1.Akiyama H, Furukawa S, Wakisaka S, Maeda T. Cartducin stimulates mesenchymal chondroprogenitor cell proliferation through both extracellular signal‐regulated kinase and phosphatidylinositol 3‐kinase/Akt pathways. FEBS J 273: 2257‐2263, 2006.
 2.Akiyama H, Furukawa S, Wakisaka S, Maeda T. CTRP3/cartducin promotes proliferation and migration of endothelial cells. Mol Cell Biochem 304: 243‐248, 2007.
 3.Akiyama H, Furukawa S, Wakisaka S, Maeda T. Elevated expression of CTRP3/cartducin contributes to promotion of osteosarcoma cell proliferation. Oncol Rep 21: 1477‐1481, 2009.
 4.Alberti KG, Zimmet PZ. Definition, diagnosis and classification of diabetes mellitus and its complications. Part 1: Diagnosis and classification of diabetes mellitus provisional report of a WHO consultation. Diabet Med 15: 539‐553, 1998.
 5.Ban B, Bai B, Zhang M, Hu J, Ramanjaneya M, Tan BK, Chen J. Low serum cartonectin/CTRP3 concentrations in newly diagnosed type 2 diabetes mellitus: In vivo regulation of cartonectin by glucose. PLoS One 9: e112931, 2014.
 6.Bannister AJ, Brown HJ, Sutherland JA, Kouzarides T. Phosphorylation of the c‐Fos and c‐Jun HOB1 motif stimulates its activation capacity. Nucleic Acids Res 22: 5173‐5176, 1994.
 7.Byerly MS, Petersen PS, Ramamurthy S, Seldin MM, Lei X, Provost E, Wei Z, Ronnett GV, Wong GW. 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. J Biol Chem 289: 4055‐4069, 2014.
 8.Byerly MS, Swanson R, Wei Z, Seldin MM, McCulloh PS, Wong GW. A central role for C1q/TNF‐related protein 13 (CTRP13) in modulating food intake and body weight. PLoS One 8: e62862, 2013.
 9.Chen NN, He JR, Li WD, Kuang YS, Yuan MY, Liu XD, Zhang HZ, Hu SP, Xia HM, Qiu X. C1q and tumor necrosis factor‐related protein 3 is present in human cord blood and is associated with fetal growth. Clin Chim Acta 453: 67‐70, 2016.
 10.Choi HY, Park JW, Lee N, Hwang SY, Cho GJ, Hong HC, Yoo HJ, Hwang TG, Kim SM, Baik SH, Park KS, Youn BS, Choi KM. Effects of a combined aerobic and resistance exercise program on C1q/TNF‐related protein‐3 (CTRP‐3) and CTRP‐5 levels. Diabetes Care 36: 3321‐3327, 2013.
 11.Choi KM, Hwang SY, Hong HC, Choi HY, Yoo HJ, Youn BS, Baik SH, Seo HS. Implications of C1q/TNF‐related protein‐3 (CTRP‐3) and progranulin in patients with acute coronary syndrome and stable angina pectoris. Cardiovasc Diabetol 13: 14, 2014.
 12.Choi KM, Hwang SY, Hong HC, Yang SJ, Choi HY, Yoo HJ, Lee KW, Nam MS, Park YS, Woo JT, Kim YS, Choi DS, Youn BS, Baik SH. C1q/TNF‐related protein‐3 (CTRP‐3) and pigment epithelium‐derived factor (PEDF) concentrations in patients with type 2 diabetes and metabolic syndrome. Diabetes 61: 2932‐2936, 2012.
 13.Compton SA, Cheatham B. CTRP‐3: Blocking a toll booth to obesity‐related inflammation. Endocrinology 151: 5095‐5097, 2010.
 14.Deng W, Li C, Zhang Y, Zhao J, Yang M, Tian M, Li L, Zheng Y, Chen B, Yang G. Serum C1q/TNF‐related protein‐3 (CTRP3) levels are decreased in obesity and hypertension and are negatively correlated with parameters of insulin resistance. Diabetol Metab Syndr 7: 33, 2015.
 15.Feng H, Wang JY, Zheng M, Zhang CL, An YM, Li L, Wu LL. CTRP3 promotes energy production by inducing mitochondrial ROS and up‐expression of PGC‐1alpha in vascular smooth muscle cells. Exp Cell Res 341: 177‐186, 2016.
 16.Flehmig G, Scholz M, Kloting N, Fasshauer M, Tonjes A, Stumvoll M, Youn BS, Bluher M. Identification of adipokine clusters related to parameters of fat mass, insulin sensitivity and inflammation. PLoS One 9: e99785, 2014.
 17.Gaziano T, Reddy KS, Paccaud F, Horton S, Chaturvedi V. Cardiovascular disease. In: Jamison DT, Breman JG, Measham AR, Alleyne G, Claeson M, Evans DB, Jha P, Mills A, Musgrove P, editors. Disease Control Priorities in Developing Countries, 2nd edition. Washington (DC): World Bank, 2006.
 18.Graziani F, Biasucci LM, Cialdella P, Liuzzo G, Giubilato S, Della Bona R, Pulcinelli FM, Iaconelli A, Mingrone G, Crea F. Thromboxane production in morbidly obese subjects. Am J Cardiol 107: 1656‐1661, 2011.
 19.Hada Y, Yamauchi T, Waki H, Tsuchida A, Hara K, Yago H, Miyazaki O, Ebinuma H, Kadowaki T. Selective purification and characterization of adiponectin multimer species from human plasma. Biochem Biophys Res Commun 356: 487‐493, 2007.
 20.Hirose H, Yamamoto Y, Seino‐Yoshihara Y, Kawabe H, Saito I. Serum high‐molecular‐weight adiponectin as a marker for the evaluation and care of subjects with metabolic syndrome and related disorders. J Atheroscler Thromb 17: 1201‐1211, 2010.
 21.Hofmann C, Chen N, Obermeier F, Paul G, Buchler C, Kopp A, Falk W, Schaffler A. C1q/TNF‐related protein‐3 (CTRP‐3) is secreted by visceral adipose tissue and exerts antiinflammatory and antifibrotic effects in primary human colonic fibroblasts. Inflamm Bowel Dis 17: 2462‐2471, 2011.
 22.Hotamisligil GS, Shargill NS, Spiegelman BM. Adipose expression of tumor necrosis factor‐alpha: Direct role in obesity‐linked insulin resistance. Science 259: 87‐91, 1993.
 23.Hou Q, Lin J, Huang W, Li M, Feng J, Mao X. CTRP3 stimulates proliferation and anti‐apoptosis of prostate cells through PKC signaling pathways. PLoS One 10: e0134006, 2015.
 24.Jostock T, Mullberg J, Ozbek S, Atreya R, Blinn G, Voltz N, Fischer M, Neurath MF, Rose‐John S. Soluble gp130 is the natural inhibitor of soluble interleukin‐6 receptor transsignaling responses. Eur J Biochem 268: 160‐167, 2001.
 25.Kambara T, Ohashi K, Shibata R, Ogura Y, Maruyama S, Enomoto T, Uemura Y, Shimizu Y, Yuasa D, Matsuo K, Miyabe M, Kataoka Y, Murohara T, Ouchi N. CTRP9 protein protects against myocardial injury following ischemia‐reperfusion through AMP‐activated protein kinase (AMPK)‐dependent mechanism. J Biol Chem 287: 18965‐18973, 2012.
 26.Kaur J. A comprehensive review on metabolic syndrome. Cardiol Res Pract 2014: 943162, 2014.
 27.Kim JY, Min JY, Baek JM, Ahn SJ, Jun HY, Yoon KH, Choi MK, Lee MS, Oh J. CTRP3 acts as a negative regulator of osteoclastogenesis through AMPK‐c‐Fos‐NFATc1 signaling in vitro and RANKL‐induced calvarial bone destruction in vivo. Bone 79: 242‐251, 2015.
 28.Kim MJ, Park EJ, Lee W, Kim JE, Park SY. Regulation of the transcriptional activation of CTRP3 in chondrocytes by c‐Jun. Mol Cell Biochem 368: 111‐117, 2012.
 29.Klonisch T, Glogowska A, Thanasupawat T, Burg M, Krcek J, Pitz M, Jaggupilli A, Chelikani P, Wong GW, Hombach‐Klonisch S. Structural commonality of C1q Tumor Necrosis Factor‐related proteins and their potential to activate RXFP1 signaling pathways in cancer cells. Br J Pharmacol 2016.
 30.Kopp A, Bala M, Buechler C, Falk W, Gross P, Neumeier M, Scholmerich J, Schaffler A. C1q/TNF‐related protein‐3 represents a novel and endogenous lipopolysaccharide antagonist of the adipose tissue. Endocrinology 151: 5267‐5278, 2010.
 31.Kopp A, Bala M, Weigert J, Buchler C, Neumeier M, Aslanidis C, Scholmerich J, Schaffler A. Effects of the new adiponectin paralogous protein CTRP‐3 and of LPS on cytokine release from monocytes of patients with type 2 diabetes mellitus. Cytokine 49: 51‐57, 2010.
 32.Lara‐Castro C, Luo N, Wallace P, Klein RL, Garvey WT. Adiponectin multimeric complexes and the metabolic syndrome trait cluster. Diabetes 55: 249‐259, 2006.
 33.Lei X, Li Q, Rodriguez S, Tan SY, Seldin MM, McLenithan JC, Jia W, Wong GW. Thromboxane synthase deficiency improves insulin action and attenuates adipose tissue fibrosis. Am J Physiol Endocrinol Metab 308: E792‐E804, 2015.
 34.Li D, Wu Y, Tian P, Zhang X, Wang H, Wang T, Ying B, Wang L, Shen Y, Wen F. Adipokine CTRP‐5 as a potential novel inflammatory biomarker in chronic obstructive pulmonary disease. Medicine (Baltimore) 94: e1503, 2015.
 35.Li JM, Zhang X, Nelson PR, Odgren PR, Nelson JD, Vasiliu C, Park J, Morris M, Lian J, Cutler BS, Newburger PE. Temporal evolution of gene expression in rat carotid artery following balloon angioplasty. J Cell Biochem 101: 399‐410, 2007.
 36.Li W, Cowley A, Uludag M, Gur T, McWilliam H, Squizzato S, Park YM, Buso N, Lopez R. The EMBL‐EBI bioinformatics web and programmatic tools framework. Nucleic Acids Res 43: W580‐W584, 2015.
 37.Li X, Jiang L, Yang M, Wu Y, Sun S, Sun J. GLP‐1 receptor agonist increases the expression of CTRP3, a novel adipokine, in 3T3‐L1 adipocytes through PKA signal pathway. J Endocrinol Invest 38: 73‐79, 2015.
 38.Li X, Jiang L, Yang M, Wu YW, Sun JZ, Sun SX. CTRP3 improves the insulin sensitivity of 3T3‐L1 adipocytes by inhibiting inflammation and ameliorating insulin signalling transduction. Endokrynol Pol 65: 252‐258, 2014.
 39.Li X, Jiang L, Yang M, Wu YW, Sun SX, Sun JZ. CTRP3 modulates the expression and secretion of adipokines in 3T3‐L1 adipocytes. Endocr J 61: 1153‐1162, 2014.
 40.Li X, Jiang L, Yang M, Wu YW, Sun SX, Sun JZ. Expression of CTRP3, a novel adipokine, in rats at different pathogenic stages of type 2 diabetes mellitus and the impacts of GLP‐1 receptor agonist on it. J Diabetes Res 2014: 398518, 2014.
 41.Li Y, Ozment T, Wright GL, Peterson JM. Identification of putative receptors for the novel adipokine CTRP3 using ligand‐receptor capture technology. Plos One 11: e0164593, 2016.
 42.Lin S, Ma S, Lu P, Cai W, Chen Y, Sheng J. Effect of CTRP3 on activation of adventitial fibroblasts induced by TGF‐beta1 from rat aorta in vitro. Int J Clin Exp Pathol 7: 2199‐2208, 2014.
 43.Maeda T, Abe M, Kurisu K, Jikko A, Furukawa S. Molecular cloning and characterization of a novel gene, CORS26, encoding a putative secretory protein and its possible involvement in skeletal development. J Biol Chem 276: 3628‐3634, 2001.
 44.Maeda T, Jikko A, Abe M, Yokohama‐Tamaki T, Akiyama H, Furukawa S, Takigawa M, Wakisaka S. Cartducin, a paralog of Acrp30/adiponectin, is induced during chondrogenic differentiation and promotes proliferation of chondrogenic precursors and chondrocytes. J Cell Physiol 206: 537‐544, 2006.
 45.Maeda T, Wakisaka S. CTRP3/cartducin is induced by transforming growth factor‐beta1 and promotes vascular smooth muscle cell proliferation. Cell Biol Int 34: 261‐266, 2010.
 46.Murayama MA, Kakuta S, Maruhashi T, Shimizu K, Seno A, Kubo S, Sato N, Saijo S, Hattori M, Iwakura Y. CTRP3 plays an important role in the development of collagen‐induced arthritis in mice. Biochem Biophys Res Commun 443: 42‐48, 2014.
 47.Otani M, Kogo M, Furukawa S, Wakisaka S, Maeda T. The adiponectin paralog C1q/TNF‐related protein 3 (CTRP3) stimulates testosterone production through the cAMP/PKA signaling pathway. Cytokine 58: 238‐244, 2012.
 48.Petersen PS, Wolf RM, Lei X, Peterson JM, Wong GW. Immunomodulatory roles of CTRP3 in endotoxemia and metabolic stress. Physiol Rep 4: 2016.
 49.Peterson JM, Aja S, Wei Z, Wong GW. CTRP1 protein enhances fatty acid oxidation via AMP‐activated protein kinase (AMPK) activation and acetyl‐CoA carboxylase (ACC) inhibition. J Biol Chem 287: 1576‐1587, 2012.
 50.Peterson JM, Seldin MM, Wei Z, Aja S, Wong GW. CTRP3 attenuates diet‐induced hepatic steatosis by regulating triglyceride metabolism. Am J Physiol Gastrointest Liver Physiol 305: G214‐G224, 2013.
 51.Peterson JM, Wei Z, Wong GW. C1q/TNF‐related protein‐3 (CTRP3), a novel adipokine that regulates hepatic glucose output. J Biol Chem 285: 39691‐39701, 2010.
 52.Qu H, Deng M, Wang H, Wei H, Liu F, Wu J, Deng H. Plasma CTRP‐3 concentrations in Chinese patients with obesity and type II diabetes negatively correlate with insulin resistance. J Clin Lipidol 9: 289‐294, 2015.
 53.Schaffler A, Ehling A, Neumann E, Herfarth H, Paul G, Tarner I, Gay S, Buechler C, Scholmerich J, Muller‐Ladner U. Role of specificity protein‐1, PPARgamma, and pituitary protein transcription factor‐1 in transcriptional regulation of the murine CORS‐26 promoter. Biochim Biophys Acta 1678: 150‐156, 2004.
 54.Schaffler A, Ehling A, Neumann E, Herfarth H, Paul G, Tarner I, Gay S, Scholmerich J, Muller‐Ladner U. Genomic organization, promoter, amino acid sequence, chromosomal localization, and expression of the human gene for CORS‐26 (collagenous repeat‐containing sequence of 26‐kDa protein). Biochim Biophys Acta 1630: 123‐129, 2003.
 55.Schaffler A, Ehling A, Neumann E, Herfarth H, Tarner I, Gay S, Scholmerich J, Muller‐Ladner U. Genomic organization, chromosomal localization and adipocytic expression of the murine gene for CORS‐26 (collagenous repeat‐containing sequence of 26 kDa protein). Biochim Biophys Acta 1628: 64‐70, 2003.
 56.Schaffler A, Weigert J, Neumeier M, Scholmerich J, Buechler C. Regulation and function of collagenous repeat containing sequence of 26‐kDa protein gene product “cartonectin”. Obesity (Silver Spring) 15: 303‐313, 2007.
 57.Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. Journal of Biological chemistry 270: 26746‐26749, 1995.
 58.Schmid A, Kopp A, Aslanidis C, Wabitsch M, Muller M, Schaffler A. Regulation and function of C1Q/TNF‐related protein‐5 (CTRP‐5) in the context of adipocyte biology. Exp Clin Endocrinol Diabetes 121: 310‐317, 2013.
 59.Schmid A, Kopp A, Hanses F, Bala M, Muller M, Schaffler A. The novel adipokine C1q/TNF‐related protein‐3 is expressed in human adipocytes and regulated by metabolic and infection‐related parameters. Exp Clin Endocrinol Diabetes 120: 611‐617, 2012.
 60.Schmid A, Kopp A, Hanses F, Karrasch T, Schaffler A. C1q/TNF‐related protein‐3 (CTRP‐3) attenuates lipopolysaccharide (LPS)‐induced systemic inflammation and adipose tissue Erk‐1/‐2 phosphorylation in mice in vivo. Biochem Biophys Res Commun 452: 8‐13, 2014.
 61.Seldin MM, Tan SY, Wong GW. Metabolic function of the CTRP family of hormones. Rev Endocr Metab Disord 15: 111‐123, 2014.
 62.Shapiro L, Scherer PE. The crystal structure of a complement‐1q family protein suggests an evolutionary link to tumor necrosis factor. Current Biology 8: 335‐340, 1998.
 63.Smith SC, Jr. Multiple risk factors for cardiovascular disease and diabetes mellitus. Am J Med 120: S3‐S11, 2007.
 64.Su H, Yuan Y, Wang XM, Lau WB, Wang Y, Wang X, Gao E, Koch WJ, Ma XL. Inhibition of CTRP9, a novel and cardiac‐abundantly expressed cell survival molecule, by TNFalpha‐initiated oxidative signaling contributes to exacerbated cardiac injury in diabetic mice. Basic Res Cardiol 108: 315, 2013.
 65.Tan BK, Chen J, Hu J, Amar O, Mattu HS, Adya R, Patel V, Ramanjaneya M, Lehnert H, Randeva HS. Metformin increases the novel adipokine cartonectin/CTRP3 in women with polycystic ovary syndrome. J Clin Endocrinol Metab 98: E1891‐E1900, 2013.
 66.Wagner RM, Sivagnanam K, Clark WA, Peterson JM. Divergent relationship of circulating CTRP3 levels between obesity and gender: a cross‐sectional study. PeerJ 4: e2573, 2016.
 67.Wang S, Zhou Y, Yang B, Li L, Yu S, Chen Y, Zhu J. C1q/tumor necrosis factor‐related protein‐3 attenuates brain injury after intracerebral hemorrhage via AMPK‐dependent pathway in rat. Front Cell Neurosci 10: 237, 2016.
 68.Wei Z, Peterson JM, Lei X, Cebotaru L, Wolfgang MJ, Baldeviano GC, Wong GW. C1q/TNF‐related protein‐12 (CTRP12), a novel adipokine that improves insulin sensitivity and glycemic control in mouse models of obesity and diabetes. J Biol Chem 287: 10301‐10315, 2012.
 69.Wei Z, Peterson JM, Wong GW. Metabolic regulation by C1q/TNF‐related protein‐13 (CTRP13): activation OF AMP‐activated protein kinase and suppression of fatty acid‐induced JNK signaling. J Biol Chem 286: 15652‐15665, 2011.
 70.Weigert J, Neumeier M, Schaffler A, Fleck M, Scholmerich J, Schutz C, Buechler C. The adiponectin paralog CORS‐26 has anti‐inflammatory properties and is produced by human monocytic cells. FEBS Lett 579: 5565‐5570, 2005.
 71.Wolf RM, Lei X, Yang ZC, Nyandjo M, Tan SY, Wong GW. CTRP3 deficiency reduces liver size and alters IL‐6 and TGFbeta levels in obese mice. Am J Physiol Endocrinol Metab 310: E332‐E345, 2016.
 72.Wolf RM, Steele KE, Peterson LA, Magnuson TH, Schweitzer MA, Wong GW. Lower circulating C1q/TNF‐related protein‐3 (CTRP3) levels are associated with obesity: A cross‐sectional study. PLoS One 10: e0133955, 2015.
 73.Wolfing B, Buechler C, Weigert J, Neumeier M, Aslanidis C, Schoelmerich J, Schaffler A. Effects of the new C1q/TNF‐related protein (CTRP‐3) “cartonectin” on the adipocytic secretion of adipokines. Obesity (Silver Spring) 16: 1481‐1486, 2008.
 74.Wong GW, Krawczyk SA, Kitidis‐Mitrokostas C, Ge G, Spooner E, Hug C, Gimeno R, Lodish HF. Identification and characterization of CTRP9, a novel secreted glycoprotein, from adipose tissue that reduces serum glucose in mice and forms heterotrimers with adiponectin. FASEB J 23: 241‐258, 2009.
 75.Wong GW, Krawczyk SA, Kitidis‐Mitrokostas C, Revett T, Gimeno R, Lodish HF. Molecular, biochemical and functional characterizations of C1q/TNF family members: adipose‐tissue‐selective expression patterns, regulation by PPAR‐gamma agonist, cysteine‐mediated oligomerizations, combinatorial associations and metabolic functions. Biochem J 416: 161‐177, 2008.
 76.Wong GW, Wang J, Hug C, Tsao TS, Lodish HF. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci U S A 101: 10302‐10307, 2004.
 77.Wu D, Lei H, Wang JY, Zhang CL, Feng H, Fu FY, Li L, Wu LL. CTRP3 attenuates post‐infarct cardiac fibrosis by targeting Smad3 activation and inhibiting myofibroblast differentiation. J Mol Med (Berl) 93: 1311‐1325, 2015.
 78.Wurm S, Neumeier M, Weigert J, Schaffler A, Buechler C. Plasma levels of leptin, omentin, collagenous repeat‐containing sequence of 26‐kDa protein (CORS‐26) and adiponectin before and after oral glucose uptake in slim adults. Cardiovasc Diabetol 6: 7, 2007.
 79.Yanai N, Satoh T, Obinata M. Endothelial cells create a hematopoietic inductive microenvironment preferential to erythropoiesis in the mouse spleen. Cell Struct Funct 16: 87‐93, 1991.
 80.Yang B, Wang S, Yu S, Chen Y, Li L, Zhang H, Zhao Y. C1q/tumor necrosis factor‐related protein 3 inhibits oxidative stress during intracerebral hemorrhage via PKA signaling. Brain Res 1657: 176‐184, 2017.
 81.Yi W, Sun Y, Yuan Y, Lau WB, Zheng Q, Wang X, Wang Y, Shang X, Gao E, Koch WJ, Ma XL. C1q/tumor necrosis factor‐related protein‐3, a newly identified adipokine, is a novel antiapoptotic, proangiogenic, and cardioprotective molecule in the ischemic mouse heart. Circulation 125: 3159‐3169, 2012.
 82.Yokohama‐Tamaki T, Maeda T, Tanaka TS, Shibata S. Functional analysis of CTRP3/cartducin in Meckel's cartilage and developing condylar cartilage in the fetal mouse mandible. J Anat 218: 517‐533, 2011.
 83.Yoo HJ, Hwang SY, Hong HC, Choi HY, Yang SJ, Choi DS, Baik SH, Bluher M, Youn BS, Choi KM. Implication of progranulin and C1q/TNF‐related protein‐3 (CTRP3) on inflammation and atherosclerosis in subjects with or without metabolic syndrome. PLoS One 8: e55744, 2013.
 84.Yuasa D, Ohashi K, Shibata R, Mizutani N, Kataoka Y, Kambara T, Uemura Y, Matsuo K, Kanemura N, Hayakawa S, Hiramatsu‐Ito M, Ito M, Ogawa H, Murate T, Murohara T, Ouchi N. C1q/TNF‐related protein‐1 functions to protect against acute ischemic injury in the heart. FASEB J 30: 1065‐1075, 2016.
 85.Zhang CL, Feng H, Li L, Wang JY, Wu D, Hao YT, Wang Z, Zhang Y, Wu LL. Globular CTRP3 promotes mitochondrial biogenesis in cardiomyocytes through AMPK/PGC‐1alpha pathway. Biochim Biophys Acta 1861: 3085‐3094, 2016.
 86.Zhang R, Zhong L, Zhou J, Peng Y. Complement‐C1q TNF‐related protein 3 alleviates mesangial cell activation and inflammatory response stimulated by secretory IgA. Am J Nephrol 43: 460‐468, 2016.
 87.Zhang Y, Proenca R, Maffei M, Barone M, Leopold L, Friedman JM. Positional cloning of the mouse obese gene and its human homologue. Nature 372: 425‐432, 1994.
 88.Zhao M, Zheng S, Yang J, Wu Y, Ren Y, Kong X, Li W, Xuan J. Suppression of TGF‐beta1/Smad signaling pathway by sesamin contributes to the attenuation of myocardial fibrosis in spontaneously hypertensive rats. PLoS One 10: e0121312, 2015.
 89.Zheng Q, Yuan Y, Yi W, Lau WB, Wang Y, Wang X, Sun Y, Lopez BL, Christopher TA, Peterson JM, Wong GW, Yu S, Yi D, Ma XL. C1q/TNF‐related proteins, a family of novel adipokines, induce vascular relaxation through the adiponectin receptor‐1/AMPK/eNOS/nitric oxide signaling pathway. Arterioscler Thromb Vasc Biol 31: 2616‐2623, 2011.
 90.Zhou Y, Wang JY, Feng H, Wang C, Li L, Wu D, Lei H, Li H, Wu LL. Overexpression of c1q/tumor necrosis factor‐related protein‐3 promotes phosphate‐induced vascular smooth muscle cell calcification both in vivo and in vitro. Arterioscler Thromb Vasc Biol 34: 1002‐1010, 2014.

Teaching Material


Y. Li, G. L. Wright, J. M. Peterson. C1q/TNF-Related Protein 3 (CTRP3) Function and Regulation. Compr Physiol 7 2017, 863-878.


Didactic Synopsis







This article summarizes the current research on CTRP3 at the graduate level.




Major Teaching Points:








  • Because of its size repeating amino acid sequence in the collagen domain CTRP3 was originally named CORS26 (Collagenous repeat-containing sequence 26 kDa protein), but later renamed as CTRP3 as it is one of many member of protein family designated as C1q TNF-related proteins. CTRP3 is a secreted protein and circulates in the blood.


  • Peroxisome proliferator-activated receptor-gamma (PPAR-γ), specificity protein 1 (SP-1), and c-FOS decreased CTRP3 expression and the transcription factor c-Jun is the only known transcription factor which increases CTRP3 expression.


  • CTRP3 increases liver lipid metabolism, reduces the amount of damage and improves recovery following a heart attack, and inhibits inflammation.


  • Although research indicates that CTRP3 appears to prevent arthritis and repair cartilage, CTRP3 may also increase the development of certain types of bone cancers osteosarcoma and chondroblastoma.


  • The function of CTRP3 is still being actively investigated as well as its role in human health especially in regards to Fatty liver and metabolic syndrome.




Didactic Legends


The figures—in a freely downloadable PowerPoint format—can be found on the Images tab along with the formal legends published in the article. The following legends to the same figures are written to be useful for teaching.



Figure 1. Teaching points: This figure highlights the two different versions of CTRP3 protein that can be made from the same RNA sequence. In addition this figure also highlights the four major domains of CTRP3 that are characteristic of all CTRP proteins: the signal peptide (SP), the N-terminal domain, the collagen domain (marked by 21 Gly-X-Y repeats), and the signature C1q domain.







Related Articles:

Steatosis in the Liver
Role of Complement and Complement‐Related Adipokines in Regulation of Energy Metabolism and Fat Storage
Contribution of Adipose Tissue Inflammation to the Development of Type 2 Diabetes Mellitus

Contact Editor

Submit a note to the editor about this article by filling in the form below.

* Required Field

How to Cite

Ying Li, Gary L. Wright, Jonathan M. Peterson. C1q/TNF‐Related Protein 3 (CTRP3) Function and Regulation. Compr Physiol 2017, 7: 863-878. doi: 10.1002/cphy.c160044