CTRP3 deficiency reduces liver size and alters IL-6 and TGFβ levels in obese mice

American Journal of Physiology - Endocrinology and Metabolism

Volumn 310, Issue 5, 2016, Pages E332-E345

  Wolf, Risa M ^a   Lei, Xia ^a   Yang, Zhi Chun ^a,b   Nyandjo, Maeva ^a   Tan, Stefanie Y ^a   William Wong, G ^a  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b CENTRAL SOUTH UNIVERSITY   (China)

Author keywords

Adipokine; C1q tumor necrosis factor; C1q tumor necrosis factor related protein; Diabetes; Fatty liver; Obesity

Indexed keywords

C1Q TUMOR NECROSIS FACTOR RELATED PROTEIN 3; GLUCOSE; INSULIN; INTERLEUKIN 6; REGULATOR PROTEIN; TRANSFORMING GROWTH FACTOR BETA1; TRIACYLGLYCEROL; UNCLASSIFIED DRUG; ADIPOCYTOKINE; CCL2 PROTEIN, MOUSE; CORS26 PROTEIN, MOUSE; DIACYLGLYCEROL ACYLTRANSFERASE; GLYCEROL 3 PHOSPHATE ACYLTRANSFERASE; MACROPHAGE ELASTASE; MATRIX METALLOPEPTIDASE 12, MOUSE; MONOCYTE CHEMOTACTIC PROTEIN 1; TGFB1 PROTEIN, MOUSE; TRANSCRIPTOME; TUMOR NECROSIS FACTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANIMAL TISSUE; ARTICLE; BLOOD CHEMISTRY; BODY COMPOSITION; CONTROLLED STUDY; ENERGY BALANCE; ENERGY EXPENDITURE; FATTY ACID OXIDATION; FEMALE; FOOD INTAKE; GENE EXPRESSION; GLUCONEOGENESIS; GLUCOSE BLOOD LEVEL; GLUCOSE HOMEOSTASIS; GLUCOSE METABOLISM; GLUCOSE TOLERANCE TEST; HISTOLOGY; HOMEOSTASIS; INDIRECT CALORIMETRY; INFLAMMATION; INSULIN BLOOD LEVEL; INSULIN SENSITIVITY; KNOCKOUT MOUSE; LIPID DIET; LIPID LIVER LEVEL; LIPOGENESIS; LIVER SIZE; LOSS OF FUNCTION MUTATION; LOW FAT DIET; MALE; METABOLIC PARAMETERS; METABOLIC RATE; METABOLIC REGULATION; MOUSE; MOUSE MODEL; NONHUMAN; OBESITY; OUTCOME ASSESSMENT; PHYSICAL ACTIVITY; PRIORITY JOURNAL; REAL TIME POLYMERASE CHAIN REACTION; WEIGHT GAIN; WHITE ADIPOSE TISSUE; WILD TYPE MOUSE; ADIPOSE TISSUE; ANIMAL; GENETICS; INSULIN RESISTANCE; LIPID METABOLISM; LIVER; METABOLISM; ORGAN SIZE; OXIDATION REDUCTION REACTION; PATHOLOGY; REVERSE TRANSCRIPTION POLYMERASE CHAIN REACTION;

ADIPOKINES; ADIPOSE TISSUE; ANIMALS; CALORIMETRY, INDIRECT; CHEMOKINE CCL2; DIACYLGLYCEROL O-ACYLTRANSFERASE; DIET, FAT-RESTRICTED; DIET, HIGH-FAT; FEMALE; GLUCONEOGENESIS; GLUCOSE; GLUCOSE TOLERANCE TEST; GLYCEROL-3-PHOSPHATE O-ACYLTRANSFERASE; INFLAMMATION; INSULIN RESISTANCE; INTERLEUKIN-6; LIPID METABOLISM; LIVER; MALE; MATRIX METALLOPROTEINASE 12; MICE; MICE, KNOCKOUT; OBESITY; ORGAN SIZE; OXIDATION-REDUCTION; REAL-TIME POLYMERASE CHAIN REACTION; REVERSE TRANSCRIPTASE POLYMERASE CHAIN REACTION; TRANSCRIPTOME; TRANSFORMING GROWTH FACTOR BETA1; TUMOR NECROSIS FACTOR-ALPHA; WEIGHT GAIN;

EID: 84983805371     PISSN: 01931849     EISSN: 15221555     Source Type: Journal    
DOI: 10.1152/ajpendo.00248.2015     Document Type: Article

References (73)

1. Akiyama H, Furukawa S, Wakisaka S, Maeda T. CTRP3/cartducin promotes proliferation and migration of endothelial cells. Mol Cell Biochem 304: 243–248, 2007.
2. 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.
3. 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.
4. Bell RM, Coleman RA. Enzymes of glycerolipid synthesis in eukaryotes. Annu Rev Biochem 49: 459–487, 1980.
5. Butler AA, Kozak LP. A recurring problem with the analysis of energy expenditure in genetic models expressing lean and obese phenotypes. Diabetes 59: 323–329, 2010.
6. 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.
7. 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.
8. 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-de- rived factor (PEDF) concentrations in patients with type 2 diabetes and metabolic syndrome. Diabetes 61: 2932–2936, 2012.
9. 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.
10. Ding EL, Song Y, Manson JE, Hunter DJ, Lee CC, Rifai N, Buring JE, Gaziano JM, Liu S. Sex hormone-binding globulin and risk of type 2 diabetes in women and men. N Engl J Med 361: 1152–1163, 2009.
11. Friedman JM, Halaas JL. Leptin and the regulation of body weight in mammals. Nature 395: 763–770, 1998.
12. Gui Y, Silha JV, Murphy LJ. Sexual dimorphism and regulation of resistin, adiponectin, and leptin expression in the mouse. Obes Res 12: 1481–1491, 2004.
13. Haber BA, Chin S, Chuang E, Buikhuisen W, Naji A, Taub R. High levels of glucose-6-phosphatase gene and protein expression reflect an adaptive response in proliferating liver and diabetes. J Clin Invest 95: 832–841, 1995.
14. Harman-Boehm I, Bluher M, Redel H, Sion-Vardy N, Ovadia S, Avinoach E, Shai I, Kloting N, Stumvoll M, Bashan N, Rudich A. Macrophage infiltration into omental versus subcutaneous fat across different populations: effect of regional adiposity and the comorbidities of obesity. J Clin Endocrinol Metab 92: 2240–2247, 2007.
15. 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.
16. Hotamisligil GS. Inflammation and metabolic disorders. Nature 444: 860–867, 2006.
17. Kadowaki T, Yamauchi T, Kubota N, Hara K, Ueki K, Tobe K. Adiponectin and adiponectin receptors in insulin resistance, diabetes, and the metabolic syndrome. J Clin Invest 116: 1784–1792, 2006.
18. Khan T, Muise ES, Iyengar P, Wang ZV, Chandalia M, Abate N, Zhang BB, Bonaldo P, Chua S, Scherer PE. Metabolic dysregulation and adipose tissue fibrosis: role of collagen VI. Mol Cell Biol 29: 1575–1591, 2009.
19. Kim HJ, Higashimori T, Park SY, Choi H, Dong J, Kim YJ, Noh HL, Cho YR, Cline G, Kim YB, Kim JK. Differential effects of interleukin-6 and -10 on skeletal muscle and liver insulin action in vivo. Diabetes 53: 1060–1067, 2004.
20. Klover PJ, Clementi AH, Mooney RA. Interleukin-6 depletion selectively improves hepatic insulin action in obesity. Endocrinology 146: 3417–3427, 2005.
21. Klover PJ, Zimmers TA, Koniaris LG, Mooney RA. Chronic exposure to interleukin-6 causes hepatic insulin resistance in mice. Diabetes 52: 2784–2789, 2003.
22. 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.
23. 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.
24. Lazar MA. Resistin- and Obesity-associated metabolic diseases. Horm Metab Res 39: 710–716, 2007.
25. Leask A, Abraham DJ. TGF-beta signaling and the fibrotic response. FASEB J 18: 816–827, 2004.
26. 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.
27. 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. Endokrynologia Polska 65: 252–258, 2014.
28. 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 J 61: 1153–1162, 2014.
29. 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.
30. 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.
31. Livak KJ, Schmittgen TD. Analysis of relative gene expression data using real-time quantitative PCR and the 2(–Delta Delta C(T)) Method. Methods 25: 402–408, 2001.
32. 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.
33. Magnusson I, Rothman DL, Katz LD, Shulman RG, Shulman GI. Increased rate of gluconeogenesis in type II diabetes mellitus. A 13C nuclear magnetic resonance study. J Clin Invest 90: 1323–1327, 1992.
34. Mayes JS, Watson GH. Direct effects of sex steroid hormones on adipose tissues and obesity. Obes Rev 5: 197–216, 2004.
35. McLean JA, Tobin G. Animal and Human Calorimetry. New York: Cambridge University, 1987.
36. 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.
37. 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.
38. Peterson JM, Aja S, Wei Z, Wong GW. C1q/TNF-related protein-1 (CTRP1) enhances fatty acid oxidation via AMPK activation and ACC inhibition. J Biol Chem 287: 1576–1587, 2012.
39. Peterson JM, Seldin MM, Tan SY, Wong GW. CTRP2 overexpression improves insulin and lipid tolerance in diet-induced obese mice. PLoS One 9: e88535, 2014.
40. 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.
41. Peterson JM, Wei Z, Seldin MM, Byerly MS, Aja S, Wong GW. CTRP9 transgenic mice are protected from diet-induced obesity and metabolic dysfunction. Am J Physiol Regul Integr Comp Physiol 305: R522–R533, 2013.
42. 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.
43. Peterson JM, Wei Z, Wong GW. CTRP8 and CTRP9B are novel proteins that hetero-oligomerize with C1q/TNF family members. Biochem Biophys Res Commun 388: 360–365, 2009.
44. Pohlers D, Brenmoehl J, Loffler I, Muller CK, Leipner C, Schultze- Mosgau S, Stallmach A, Kinne RW, Wolf G. TGF-beta and fibrosis in different organs - molecular pathway imprints. Biochim Biophys Acta 1792: 746–756, 2009.
45. Ruderman NB, Keller C, Richard AM, Saha AK, Luo Z, Xiang X, Giralt M, Ritov VB, Menshikova EV, Kelley DE, Hidalgo J, Pedersen BK, Kelly M. Interleukin-6 regulation of AMP-activated protein kinase. Potential role in the systemic response to exercise and prevention of the metabolic syndrome. Diabetes 55, Suppl 2: S48–S54, 2006.
46. Samuel VT, Beddow SA, Iwasaki T, Zhang XM, Chu X, Still CD, Gerhard GS, Shulman GI. Fasting hyperglycemia is not associated with increased expression of PEPCK or G6Pc in patients with Type 2 Diabetes. Proc Natl Acad Sci USA 106: 12121–12126, 2009.
47. Scherer PE, Williams S, Fogliano M, Baldini G, Lodish HF. A novel serum protein similar to C1q, produced exclusively in adipocytes. J Biol Chem 270: 26746–26749, 1995.
48. Schmid A, Kopp A, Hanses F, Karrasch T, Schaffler A. C1q/TNFrelated 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.
49. Seldin MM, Peterson JM, Byerly MS, Wei Z, Wong GW. Myonectin (CTRP15), a novel myokine that links skeletal muscle to systemic lipid homeostasis. J Biol Chem 287: 11968–11980 2012.
50. Seldin MM, Tan SY, Wong GW. Metabolic function of the CTRP family of hormones. Rev Endocr Metab Disord 15: 111–123, 2014.
51. Sun K, Tordjman J, Clement K, Scherer PE. Fibrosis and adipose tissue dysfunction. Cell Metab 18: 470–477, 2013.
52. Taga T, Kishimoto T. Gp130 and the interleukin-6 family of cytokines. Annu Rev Immunol 15: 797–819, 1997.
53. Takeuchi K, Reue K. Biochemistry, physiology, and genetics of GPAT, AGPAT, and lipin enzymes in triglyceride synthesis. Am J Physiol Endocrinol Metab 296: E1195–E1209, 2009.
54. 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.
55. Unger RH, Clark GO, Scherer PE, Orci L. Lipid homeostasis, lipotoxicity and the metabolic syndrome. Biochim Biophys Acta 1801: 209–214, 2010.
56. Wallenius V, Wallenius K, Ahren B, Rudling M, Carlsten H, Dickson SL, Ohlsson C, Jansson JO. Interleukin-6-deficient mice develop mature- onset obesity. Nat Med 8: 75–79, 2002.
57. Wei Z, Lei X, Petersen PS, Aja S, Wong GW. Targeted deletion of C1q/TNF-related protein 9 increases food intake, decreases insulin sensitivity, and promotes hepatic steatosis in mice. Am J Physiol Endocrinol Metab 306: E779–E790, 2014.
58. Wei Z, Lei X, Seldin MM, Wong GW. Endopeptidase cleavage generates a functionally distinct isoform of C1q/tumor necrosis factor-related protein- 12 (CTRP12) with an altered oligomeric state and signaling specificity. J Biol Chem 287: 35804–35814, 2012.
59. 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.
60. Wei Z, Peterson JM, Wong GW. Metabolic regulation by C1q/TNFrelated protein-13 (CTRP13): activation OF AMP-activated protein kinase and suppression of fatty acid-induced JNK signaling. J Biol Chem 286: 15652–15665, 2011.
61. Wei Z, Seldin MM, Natarajan N, Djemal DC, Peterson JM, Wong GW. C1q/tumor necrosis factor-related protein 11 (CTRP11), a novel adipose stroma-derived regulator of adipogenesis. J Biol Chem 288: 10214–10229, 2013.
62. Weisberg SP, McCann D, Desai M, Rosenbaum M, Leibel RL, Ferrante AW Jr. Obesity is associated with macrophage accumulation in adipose tissue. J Clin Invest 112: 1796–1808, 2003.
63. 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.
64. 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.
65. 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.
66. Wong GW, Wang J, Hug C, Tsao TS, Lodish HF. A family of Acrp30/adiponectin structural and functional paralogs. Proc Natl Acad Sci USA 101: 10302–10307, 2004.
67. Xu H, Barnes GT, Yang Q, Tan G, Yang D, Chou CJ, Sole J, Nichols A, Ross JS, Tartaglia LA, Chen H. Chronic inflammation in fat plays a crucial role in the development of obesity-related insulin resistance. J Clin Invest 112: 1821–1830, 2003.
68. Yen CL, Stone SJ, Koliwad S, Harris C, Farese RV Jr. Thematic review series: glycerolipids. DGAT enzymes and triacylglycerol biosynthesis. J Lipid Res 49: 2283–2301, 2008.
69. 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.
70. 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.
71. 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.
72. Yoon JC, Puigserver P, Chen G, Donovan J, Wu Z, Rhee J, Adelmant G, Stafford J, Kahn CR, Granner DK, Newgard CB, Spiegelman BM. Control of hepatic gluconeogenesis through the transcriptional coactivator PGC-1. Nature 413: 131–138, 2001.
73. 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.