nach oben

Journal of Endocrinological Investigation

Erschienen in:

01.02.2018 | Original Article

Peroxisome proliferator-activated receptor gamma expression in peripheral blood mononuclear cells and angiopoietin-like protein 4 levels in obese children and adolescents

verfasst von: Z. A. Sadeghabadi, M. Nourbakhsh, M. Alaee, B. Larijani, M. Razzaghy-Azar

Erschienen in: Journal of Endocrinological Investigation | Ausgabe 2/2018

Einloggen, um Zugang zu erhalten

Abstract

Purpose

The peroxisome proliferator-activated receptor γ (PPARγ) is highly expressed in adipose tissue and functions as transcriptional regulator of metabolism and adipocyte differentiation. Angiopoietin-like protein 4 (ANGPTL4), a central player in various aspects of energy homoeostasis, is induced by PPARγ. The aim of this study was to evaluate ANGPTL4 plasma levels and PPARγ gene expression in peripheral blood mononuclear cells (PBMCs) of children and adolescents with obesity and their association with metabolic parameters.

Methods

Seventy children and adolescents (35 obese and 35 age- and gender-matched control subjects), were selected. PBMCs were separated and their total RNA was extracted. After cDNA synthesis, PPARG gene expression was analyzed by real-time PCR. Relative differences in gene expression were calculated by ΔCt method using β-actin as a normalizer. Serum ANGPTL4 and insulin were measured using ELISA, and insulin resistance (IR) was calculated by the homeostatic model assessment of insulin resistance (HOMA-IR). Fasting plasma glucose (FPG), triglyceride, total cholesterol, LDL-C and HDL-C were also measured.

Results

The expression of the PPARG gene as well as the plasma ANGPTL4 levels were significantly diminished in obese subjects as compared to control ones. However, they were not significantly different in obese children with IR compared to obese children without IR or in those with or without metabolic syndrome. A significant positive correlation was found between PPARγ and ANGPTL4 (r = 0.364, p = 0.002). PPARγ expression levels were also significantly correlated with FPG (r = −0.35, p = 0.003).

Conclusion

PPARγ is decreased in childhood obesity and may be responsible for diminished ANGPTL4 levels.

Lobstein T, Baur L, Uauy R (2004) Obesity in children and young people: a crisis in public health. Obes Rev 5(s1):4–85CrossRefPubMed

De Onis M, Blössner M, Borghi E (2010) Global prevalence and trends of overweight and obesity among preschool children. Am J Clin Nutr 92(5):1257–1264CrossRefPubMed

Sookoian S, Pirola CJ (2011) Metabolic syndrome: from the genetics to the pathophysiology. Curr Hypertens Rep 13(2):149–157CrossRefPubMed

Harris M (2013) The metabolic syndrome. Aust Fam Phys 42:524–527

Lara-Castro C, Fu Y, Chung BH, Garvey WT (2007) Adiponectin and the metabolic syndrome: mechanisms mediating risk for metabolic and cardiovascular disease. Curr Opin Lipidol 18(3):263–270CrossRefPubMed

Semple RK, Chatterjee VKK, O’Rahilly S (2006) PPARγ and human metabolic disease. J Clin Investig 116(3):581–589CrossRefPubMedPubMedCentral

Lowell BB (1999) An essential regulator of adipogenesis and modulator of fat cell function: PPAR [gamma]. Cell 99(3):239–242CrossRefPubMed

Miyazaki Y, Mahankali A, Matsuda M, Mahankali S, Hardies J, Cusi K, Mandarino LJ, DeFronzo RA (2002) Effect of pioglitazone on abdominal fat distribution and insulin sensitivity in type 2 diabetic patients. J Clin Endocrinol Metab 87(6):2784–2791. doi:10.1210/jcem.87.6.8567 CrossRefPubMed

Ristow M, Müller-Wieland D, Pfeiffer A, Krone W, Kahn CR (1998) Obesity associated with a mutation in a genetic regulator of adipocyte differentiation. N Engl J Med 339(14):953–959CrossRefPubMed

10.

Saltiel AR, Olefsky JM (1996) Thiazolidinediones in the treatment of insulin resistance and type II diabetes. Diabetes 45(12):1661–1669CrossRefPubMed

11.

Barroso I, Gurnell M, Crowley V, Agostini M, Schwabe J, Soos M, Maslen GL, Williams T, Lewis H, Schafer A (1999) Dominant negative mutations in human PPARγ associated with severe insulin resistance, diabetes mellitus and hypertension. Nature 402(6764):880–883PubMed

12.

Fonseca VA, Valiquett TR, Huang SM, Ghazzi MN, Whitcomb RW (1998) Troglitazone monotherapy improves glycemic control in patients with type 2 diabetes mellitus: a randomized, controlled study 1. J Clin Endocrinol Metab 83(9):3169–3176PubMed

13.

Chappuis B, Braun M, Stettler C, Allemann S, Diem P, Lumb PJ, Wierzbicki AS, James R, Christ ER (2007) Differential effect of pioglitazone (PGZ) and rosiglitazone (RGZ) on postprandial glucose and lipid metabolism in patients with type 2 diabetes mellitus: a prospective, randomized crossover study. Diabetes/Metab Res Rev 23(5):392–399CrossRef

14.

Goldberg RB, Kendall DM, Deeg MA, Buse JB, Zagar AJ, Pinaire JA, Tan MH, Khan MA, Perez AT, Jacober SJ (2005) A comparison of lipid and glycemic effects of pioglitazone and rosiglitazone in patients with type 2 diabetes and dyslipidemia. Diabetes Care 28(7):1547–1554CrossRefPubMed

15.

Halabi CM, Beyer AM, de Lange WJ, Keen HL, Baumbach GL, Faraci FM, Sigmund CD (2008) Interference with PPAR gamma function in smooth muscle causes vascular dysfunction and hypertension. Cell Metab 7(3):215–226. doi:10.1016/j.cmet.2007.12.008 CrossRefPubMedPubMedCentral

16.

Jiang C, Ting AT, Seed B (1998) PPAR-γ agonists inhibit production of monocyte inflammatory cytokines. Nature 391(6662):82–86CrossRefPubMed

17.

Kadomatsu T, Tabata M, Oike Y (2011) Angiopoietin-like proteins: emerging targets for treatment of obesity and related metabolic diseases. FEBS J 278(4):559–564CrossRefPubMed

18.

Kim I, Moon S-O, Koh KN, Kim H, Uhm C-S, Kwak HJ, Kim N-G, Koh GY (1999) Molecular cloning, expression, and characterization of angiopoietin-related protein angiopoietin-related protein induces endothelial cell sprouting. J Biol Chem 274(37):26523–26528CrossRefPubMed

19.

Injune K, Hwan-Gyu K, Hyun K, Hong-Hee K, Park SK, Chang-Sub U, Lee ZH, Koh GY (2000) Hepatic expression, synthesis and secretion of a novel fibrinogen/angiopoietin-related protein that prevents endothelial-cell apoptosis. Biochem J 346(3):603–610CrossRef

20.

Gerber M, Boettner A, Seidel B, Lammert A, Bar J, Schuster E, Thiery J, Kiess W, Kratzsch J (2005) Serum resistin levels of obese and lean children and adolescents: biochemical analysis and clinical relevance. J Clin Endocrinol Metab 90(8):4503–4509. doi:10.1210/jc.2005-0437 CrossRefPubMed

21.

Oike Y, Akao M, Kubota Y, Suda T (2005) Angiopoietin-like proteins: potential new targets for metabolic syndrome therapy. Trends Mol Med 11(10):473–479CrossRefPubMed

22.

Yoon JC, Chickering TW, Rosen ED, Dussault B, Qin Y, Soukas A, Friedman JM, Holmes WE, Spiegelman BM (2000) Peroxisome proliferator-activated receptor γ target gene encoding a novel angiopoietin-related protein associated with adipose differentiation. Mol Cell Biol 20(14):5343–5349CrossRefPubMedPubMedCentral

23.

Yoshida K, Shimizugawa T, Ono M, Furukawa H (2002) Angiopoietin-like protein 4 is a potent hyperlipidemia-inducing factor in mice and inhibitor of lipoprotein lipase. J Lipid Res 43(11):1770–1772CrossRefPubMed

24.

Sanderson LM, Degenhardt T, Koppen A, Kalkhoven E, Desvergne B, Müller M, Kersten S (2009) Peroxisome proliferator-activated receptor β/δ (PPARβ/δ) but not PPARα serves as a plasma free fatty acid sensor in liver. Mol Cell Biol 29(23):6257–6267CrossRefPubMedPubMedCentral

25.

Kim H-K, Youn B-S, Shin M-S, Namkoong C, Park KH, Baik JH, Kim JB, Park J-Y, K-u Lee, Kim Y-B (2010) Hypothalamic Angptl4/Fiaf is a novel regulator of food intake and body weight. Diabetes 59(11):2772–2780CrossRefPubMedPubMedCentral

26.

Zhu P, Tan MJ, Huang R-L, Tan CK, Chong HC, Pal M, Lam CRI, Boukamp P, Pan JY, Tan SH (2011) Angiopoietin-like 4 protein elevates the prosurvival intracellular O₂ ⁻: H₂O₂ ratio and confers anoikis resistance to tumors. Cancer Cell 19(3):401–415CrossRefPubMed

27.

Galaup A, Cazes A, Le Jan S, Philippe J, Connault E, Le Coz E, Mekid H, Mir LM, Opolon P, Corvol P (2006) Angiopoietin-like 4 prevents metastasis through inhibition of vascular permeability and tumor cell motility and invasiveness. Proc Natl Acad Sci 103(49):18721–18726CrossRefPubMedPubMedCentral

28.

Padua D, Zhang XH-F, Wang Q, Nadal C, Gerald WL, Gomis RR, Massagué J (2008) TGFβ primes breast tumors for lung metastasis seeding through angiopoietin-like 4. Cell 133(1):66–77CrossRefPubMedPubMedCentral

29.

Ito Y, Oike Y, Yasunaga K, Hamada K, Miyata K, S-i Matsumoto, Sugano S, Tanihara H, Masuho Y, Suda T (2003) Inhibition of angiogenesis and vascular leakiness by angiopoietin-related protein 4. Can Res 63(20):6651–6657

30.

Le Jan S, Amy C, Cazes A, Monnot C, Lamandé N, Favier J, Philippe J, Sibony M, Gasc J-M, Corvol P (2003) Angiopoietin-like 4 is a proangiogenic factor produced during ischemia and in conventional renal cell carcinoma. Am J Pathol 162(5):1521–1528CrossRefPubMedPubMedCentral

31.

Goh YY, Pal M, Chong HC, Zhu P, Tan MJ, Punugu L, Tan CK, Huang R-L, Sze SK, Tang MBY (2010) Angiopoietin-like 4 interacts with matrix proteins to modulate wound healing. J Biol Chem 285(43):32999–33009CrossRefPubMedPubMedCentral

32.

Lichtenstein L, Mattijssen F, de Wit NJ, Georgiadi A, Hooiveld GJ, van der Meer R, He Y, Qi L, Köster A, Tamsma JT (2010) Angptl4 protects against severe proinflammatory effects of saturated fat by inhibiting fatty acid uptake into mesenteric lymph node macrophages. Cell Metab 12(6):580–592CrossRefPubMedPubMedCentral

33.

Clement LC, Avila-Casado C, Macé C, Soria E, Bakker WW, Kersten S, Chugh SS (2011) Podocyte-secreted angiopoietin-like-4 mediates proteinuria in glucocorticoid-sensitive nephrotic syndrome. Nat Med 17(1):117–122CrossRefPubMed

34.

Kersten S (2009) Angiopoietin-like proteins and lipid metabolism. In: Cellular lipid metabolism. Springer, Heidelberg, Germany pp 237–249

35.

Lichtenstein L, Kersten S (2010) Modulation of plasma TG lipolysis by Angiopoietin-like proteins and GPIHBP1. Biochimica et Biophysica Acta (BBA)-Mol Cell Biol Lipids 1801(4):415–420

36.

Kersten S, Lichtenstein L, Steenbergen E, Mudde K, Hendriks HFJ, Hesselink MK, Schrauwen P, Müller M (2009) Caloric restriction and exercise increase plasma ANGPTL4 levels in humans via elevated free fatty acids. Arterioscler Thromb Vasc Biol 29(6):969–974. doi:10.1161/atvbaha.108.182147 CrossRefPubMed

37.

Wang Z, Han B, Zhang Z, Pan J, Xia H (2010) Expression of angiopoietin-like 4 and tenascin C but not cathepsin C mRNA predicts prognosis of oral tongue squamous cell carcinoma. Biomarkers 15(1):39–46CrossRefPubMed

38.

Cook S, Auinger P, Huang TTK (2009) Growth curves for cardio-metabolic risk factors in children and adolescents. J Pediatr 155(3):S6.e15–S16.e26. doi:10.1016/j.jpeds.2009.04.051 CrossRef

39.

Bergman RN, Finegood DT, Ader M (1985) Assessment of insulin sensitivity in vivo. Endocr Rev 6(1):45–86. doi:10.1210/edrv-6-1-45 CrossRefPubMed

40.

Keskin M, Kurtoglu S, Kendirci M, Atabek ME, Yazici C (2005) Homeostasis model assessment is more reliable than the fasting glucose/insulin ratio and quantitative insulin sensitivity check index for assessing insulin resistance among obese children and adolescents. Pediatrics 115(4):e500–e503. doi:10.1542/peds.2004-1921 CrossRefPubMed

41.

Zimmet P, Alberti G, Kaufman F, Tajima N, Silink M, Arslanian S, Wong G, Bennett P, Shaw J, Caprio S (2007) The metabolic syndrome in children and adolescents. Lancet 369(9579):2059–2061. doi:10.1016/s0140-6736(07)60958-1 CrossRefPubMed

42.

Oliver P, Reynés B, Caimari A, Palou A (2013) Peripheral blood mononuclear cells: a potential source of homeostatic imbalance markers associated with obesity development. Pflügers Arch Eur J Physiol 465(4):459–468. doi:10.1007/s00424-013-1246-8 CrossRef

43.

Akyurek N, Aycan Z, Cetinkaya S, Akyurek O, Yilmaz Agladioglu S, Ertan U (2013) Peroxisome proliferator activated receptor (PPAR)-gamma concentrations in childhood obesity. Scand J Clin Lab Invest 73(4):355–360. doi:10.3109/00365513.2013.786121 CrossRefPubMed

44.

Li X, Lindquist S, Angsten G, Yi J, Olsson T, Hernell O (2008) Adiponectin and peroxisome proliferator-activated receptor γ expression in subcutaneous and omental adipose tissue in children. Acta Paediatr 97(5):630–635. doi:10.1111/j.1651-2227.2008.00715.x CrossRefPubMed

45.

Tontonoz P, Hu E, Graves RA, Budavari AI, Spiegelman BM (1994) mPPAR gamma 2: tissue-specific regulator of an adipocyte enhancer. Genes Dev 8(10):1224–1234CrossRefPubMed

46.

Deeb SS, Fajas L, Nemoto M, Pihlajamäki J, Mykkänen L, Kuusisto J, Laakso M, Fujimoto W, Auwerx J (1998) A Pro12Ala substitution in PPARγ2 associated with decreased receptor activity, lower body mass index and improved insulin sensitivity. Nat Genet 20(3):284–287CrossRefPubMed

47.

Larsen TM, Toubro S, Astrup A (2003) PPARgamma agonists in the treatment of type II diabetes: is increased fatness commensurate with long-term efficacy? Int J Obes Relat Metab Disorders 27(2):147–161. doi:10.1038/sj.ijo.802223 CrossRef

48.

Vidal-Puig A, Jimenez-Liñan M, Lowell BB, Hamann A, Hu E, Spiegelman B, Flier JS, Moller DE (1996) Regulation of PPAR gamma gene expression by nutrition and obesity in rodents. J Clin Investig 97(11):2553–2561CrossRefPubMedPubMedCentral

49.

Kintscher U, Law RE (2005) PPARγ-mediated insulin sensitization: the importance of fat versus muscle. Am J Physiol Endocrinol Metab 288(2):E287–E291. doi:10.1152/ajpendo.00440.2004 CrossRefPubMed

50.

Kersten S, Mandard S, Tan NS, Escher P, Metzger D, Chambon P, Gonzalez FJ, Desvergne B, Wahli W (2000) Characterization of the fasting-induced adipose factor FIAF, a novel peroxisome proliferator-activated receptor target gene. J Biol Chem 275(37):28488–28493CrossRefPubMed

51.

Wiesner G, Morash BA, Ur E, Wilkinson M (2004) Food restriction regulates adipose-specific cytokines in pituitary gland but not in hypothalamus. J Endocrinol 180(3):R1–R6CrossRefPubMed

52.

Lichtenstein L, Berbée JF, van Dijk SJ, van Dijk KW, Bensadoun A, Kema IP, Voshol PJ, Müller M, Rensen PC, Kersten S (2007) Angptl4 upregulates cholesterol synthesis in liver via inhibition of LPL-and HL-dependent hepatic cholesterol uptake. Arterioscler Thromb Vasc Biol 27(11):2420–2427CrossRefPubMed

53.

Ruge T, Sukonina V, Kroupa O, Makoveichuk E, Lundgren M, Svensson MK, Olivecrona G, Eriksson JW (2012) Effects of hyperinsulinemia on lipoprotein lipase, angiopoietin-like protein 4, and glycosylphosphatidylinositol-anchored high-density lipoprotein binding protein 1 in subjects with and without type 2 diabetes mellitus. Metabolism 61(5):652–660CrossRefPubMed

54.

Robciuc MR, Naukkarinen J, Ortega-Alonso A, Tyynismaa H, Raivio T, Rissanen A, Kaprio J, Ehnholm C, Jauhiainen M, Pietiläinen KH (2011) Serum angiopoietin-like 4 protein levels and expression in adipose tissue are inversely correlated with obesity in monozygotic twins. J Lipid Res 52(8):1575–1582. doi:10.1194/jlr.P015867 CrossRefPubMedPubMedCentral

55.

Gealekman O, Burkart A, Chouinard M, Nicoloro SM, Straubhaar J, Corvera S (2008) Enhanced angiogenesis in obesity and in response to PPARgamma activators through adipocyte VEGF and ANGPTL4 production. Am J Physiol Endocrinol Metab 295(5):E1056–E1064. doi:10.1152/ajpendo.90345.2008 CrossRefPubMedPubMedCentral

56.

Zhu P, Goh YY, Chin HF, Kersten S, Tan NS (2012) Angiopoietin-like 4: a decade of research. Biosci Rep 32(3):211–219. doi:10.1042/bsr20110102 CrossRefPubMed

Titel: Peroxisome proliferator-activated receptor gamma expression in peripheral blood mononuclear cells and angiopoietin-like protein 4 levels in obese children and adolescents
verfasst von: Z. A. Sadeghabadi
M. Nourbakhsh
M. Alaee
B. Larijani
M. Razzaghy-Azar
Publikationsdatum: 01.02.2018
Verlag: Springer International Publishing
Erschienen in: Journal of Endocrinological Investigation / Ausgabe 2/2018
Elektronische ISSN: 1720-8386
DOI: https://doi.org/10.1007/s40618-017-0730-y

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

^{Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag}

Kostenlos registrieren

Neu im Fachgebiet Innere Medizin

25.04.2024 | Nierenkarzinom | Nachrichten

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.

Newsletter bestellen

Springer Medizin

Peroxisome proliferator-activated receptor gamma expression in peripheral blood mononuclear cells and angiopoietin-like protein 4 levels in obese children and adolescents

Abstract

Purpose

Methods

Results

Conclusion

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Update Innere Medizin

Springer Medizin

Abstract

Purpose

Methods

Results

Conclusion

Bitte loggen Sie sich ein, um Zugang zu diesem Inhalt zu erhalten

Weitere Artikel der Ausgabe 2/2018

Does hypoglycaemia affect the improvement in QoL after the transition to insulin in people with type 2 diabetes?

Non-surgical ablative therapies for inoperable benign insulinoma

Varicocele and semen quality: a retrospective case–control study of 4230 patients from a single centre

A comparison of clinical efficacy and economic value in Basalin- and Lantus-treated patients with type 2 diabetes using continuous glucose monitoring system

Correction to: Pegvisomant in acromegaly: an update

Use of testosterone gel compared to intramuscular formulation for puberty induction in males with constitutional delay of growth and puberty: a preliminary study

Leitlinien kompakt für die Innere Medizin

Neu im Fachgebiet Innere Medizin

Adjuvante Immuntherapie verlängert Leben bei RCC

Alectinib verbessert krankheitsfreies Überleben bei ALK-positivem NSCLC

Metformin rückt in den Hintergrund

Myokarditis nach Infekt – richtig schwierig wird es bei Profisportlern

Update Innere Medizin