Obesity Surgery

, Volume 19, Issue 6, pp 771–776 | Cite as

RIP140 Gene and Protein Expression Levels are Downregulated in Visceral Adipose Tissue in Human Morbid Obesity

  • Victoria Catalán
  • Javier Gómez-Ambrosi
  • Amaia Lizanzu
  • Amaia Rodríguez
  • Camilo Silva
  • Fernando Rotellar
  • María J. Gil
  • Javier A. Cienfuegos
  • Javier Salvador
  • Gema FrühbeckEmail author
Clinical Research



Receptor-interacting protein 140 (RIP140) is a corepressor for nuclear receptors with an important role in the inhibition of energy expenditure. Rip140-knockout mice are lean and resistant to diet-induced obesity due to an increase in mitochondrial biogenesis, fatty acid oxidation, and oxidative phosphorylation. The aim of the present work was to evaluate the effect of morbid obesity on gene and protein expression levels of RIP140 in visceral adipose tissue (VAT).


VAT biopsies obtained from 17 subjects were used in the study. Patients were classified as lean (body mass index [BMI] = 21.8 ± 1.3 kg/m2) or obese (BMI = 48.2 ± 2.6 kg/m2). Reverse transcription polymerase chain reaction and Western blot analyses were performed to quantify the expression levels of RIP140 in VAT. We also analyzed glucose and lipid profile as well as some inflammatory factors.


Obese patients exhibited significantly lower RIP140 mRNA expression levels compared to lean subjects (lean = 1.00 ± 0.17 arbitrary units, obese = 0.65 ± 0.18 arbitrary units; P < 0.05). Protein expression of RIP140 followed the same trend, being significantly higher in lean volunteers (lean = 1.00 ± 0.18 arbitrary units, obese = 0.45 ± 0.11 arbitrary units; P < 0.05). Furthermore, a significant negative correlation was found between RIP140 protein levels and both BMI (ρ = −0.85; P < 0.001) and body fat percentage (ρ = −0.88; P < 0.001).


The lower gene and protein expression levels of RIP140 in obese subjects may suggest a compensatory mechanism in order to favor energy expenditure and reduce fat accumulation in obesity states.


Receptor-interacting protein 140 Morbid obesity Visceral adipose tissue 



receptor-interacting protein 140


body fat percentage


body mass index


visceral adipose tissue



This work was supported by FIS PI061458 and PI06/90288 from the Spanish Instituto de Salud Carlos III, Ministerio de Sanidad y Consumo, by the Department of Health of the Gobierno de Navarra (20/2005), and by the Department of Education of the Gobierno de Navarra (res228/2008) of Spain. The authors gratefully acknowledge the valuable collaboration of all the members of the Multidisciplinary Obesity Team. CIBER Fisiopatología de la Obesidad y Nutrición is an initiative of ISCIII.

Disclosure Statement

The authors have nothing to disclose.


  1. 1.
    Badman MK, Flier JS. The adipocyte as an active participant in energy balance and metabolism. Gastroenterology 2007;132:2103–15.CrossRefGoogle Scholar
  2. 2.
    Frühbeck G, Gómez-Ambrosi J. Rationale for the existence of additional adipostatic hormones. FASEB J. 2001;15:1996–2006.CrossRefGoogle Scholar
  3. 3.
    Trayhurn P. Adipocyte biology. Obes Rev. 2007;8:41–4.CrossRefGoogle Scholar
  4. 4.
    Ahima RS, Lazar MA. Adipokines and the peripheral and neural control of energy balance. Mol Endocrinol. 2008;22:1023–31.CrossRefGoogle Scholar
  5. 5.
    Mangelsdorf DJ, Thummel C, Beato M, et al. The nuclear receptor superfamily: the second decade. Cell 1995;83:835–9.CrossRefGoogle Scholar
  6. 6.
    Evans RM. The nuclear receptor superfamily: a rosetta stone for physiology. Mol Endocrinol. 2005;19:1429–38.CrossRefGoogle Scholar
  7. 7.
    Heim KC, White KA, Deng D, et al. Selective repression of retinoic acid target genes by RIP140 during induced tumor cell differentiation of pluripotent human embryonal carcinoma cells. Mol Cancer. 2007;6:57.CrossRefGoogle Scholar
  8. 8.
    Lin J, Handschin C, Spiegelman BM. Metabolic control through the PGC-1 family of transcription coactivators. Cell Metab. 2005;1:361–70.CrossRefGoogle Scholar
  9. 9.
    White R, Morganstein D, Christian M, et al. Role of RIP140 in metabolic tissues: connections to disease. FEBS Lett. 2008;582:39–45.CrossRefGoogle Scholar
  10. 10.
    Francis GA, Fayard E, Picard F, et al. Nuclear receptors and the control of metabolism. Annu Rev Physiol. 2003;65:261–311.CrossRefGoogle Scholar
  11. 11.
    Feige JN, Auwerx J. Transcriptional coregulators in the control of energy homeostasis. Trends Cell Biol. 2007;17:292–301.CrossRefGoogle Scholar
  12. 12.
    Lehrke M, Lazar MA. The many faces of PPARγ. Cell 2005;123:993–9.CrossRefGoogle Scholar
  13. 13.
    Leonardsson G, Steel JH, Christian M, et al. Nuclear receptor corepressor RIP140 regulates fat accumulation. Proc Natl Acad Sci USA. 2004;101:8437–42.CrossRefGoogle Scholar
  14. 14.
    Christian M, White R, Parker MG. Metabolic regulation by the nuclear receptor corepressor RIP140. Trends Endocrinol Metab. 2006;17:243–50.CrossRefGoogle Scholar
  15. 15.
    Parker MG, Christian M, White R. The nuclear receptor co-repressor RIP140 controls the expression of metabolic gene networks. Biochem Soc Trans. 2006;34:1103–6.CrossRefGoogle Scholar
  16. 16.
    Powelka AM, Seth A, Virbasius JV, et al. Suppression of oxidative metabolism and mitochondrial biogenesis by the transcriptional corepressor RIP140 in mouse adipocytes. J Clin Invest. 2006;116:125–36.CrossRefGoogle Scholar
  17. 17.
    Christian M, Kiskinis E, Debevec D, et al. RIP140-targeted repression of gene expression in adipocytes. Mol Cell Biol. 2005;25:9383–91.CrossRefGoogle Scholar
  18. 18.
    Augereau P, Badia E, Carascossa S, et al. The nuclear receptor transcriptional coregulator RIP140. Nucl Recept Signal. 2006;4:e024.CrossRefGoogle Scholar
  19. 19.
    Debevec D, Christian M, Morganstein D, et al. Receptor interacting protein 140 regulates expression of uncoupling protein 1 in adipocytes through specific peroxisome proliferator activated receptor isoforms and estrogen-related receptor α. Mol Endocrinol. 2007;21:1581–92.CrossRefGoogle Scholar
  20. 20.
    Kiskinis E, Hallberg M, Christian M, et al. RIP140 directs histone and DNA methylation to silence Ucp1 expression in white adipocytes. EMBO J. 2007;26:4831–40.CrossRefGoogle Scholar
  21. 21.
    Gómez-Ambrosi J, Frühbeck G, Martinez JA. Rapid in vivo PGC-1 mRNA upregulation in brown adipose tissue of Wistar rats by a β(3)-adrenergic agonist and lack of effect of leptin. Mol Cell Endocrinol. 2001;176:85–90.CrossRefGoogle Scholar
  22. 22.
    Hallberg M, Morganstein DL, Kiskinis E, et al. A functional interaction between RIP140 and PGC-1α regulates the expression of the lipid droplet protein CIDEA. Mol Cell Biol. 2008;28:6785–95.CrossRefGoogle Scholar
  23. 23.
    Das SK, Roberts SB, Kehayias JJ, et al. Body composition assessment in extreme obesity and after massive weight loss induced by gastric bypass surgery. Am J Physiol Endocrinol Metab. 2003;284:E1080–8.CrossRefGoogle Scholar
  24. 24.
    Matthews DR, Hosker JP, Rudenski AS, et al. Homeostasis model assessment: insulin resistance and β-cell function from fasting plasma glucose and insulin concentrations in man. Diabetologia 1985;28:412–9.CrossRefGoogle Scholar
  25. 25.
    Gómez-Ambrosi J, Salvador J, Rotellar F, et al. Increased serum amyloid A concentrations in morbid obesity decrease after gastric bypass. Obes Surg. 2006;16:262–9.CrossRefGoogle Scholar
  26. 26.
    Gómez-Ambrosi J, Catalán V, Diez-Caballero A, et al. Gene expression profile of omental adipose tissue in human obesity. FASEB J. 2004;18:215–7.CrossRefGoogle Scholar
  27. 27.
    Rodríguez A, Frühbeck G, Gómez-Ambrosi J, et al. The inhibitory effect of leptin on angiotensin II-induced vasoconstriction is blunted in spontaneously hypertensive rats. J Hypertens. 2006;24:1589–97.CrossRefGoogle Scholar
  28. 28.
    Fortuño A, Rodríguez A, Gómez-Ambrosi J, et al. Adipose tissue as an endocrine organ: role of leptin and adiponectin in the pathogenesis of cardiovascular diseases. J Physiol Biochem. 2003;59:51–60.CrossRefGoogle Scholar
  29. 29.
    Kahn SE, Hull RL, Utzschneider KM. Mechanisms linking obesity to insulin resistance and type 2 diabetes. Nature 2006;444:840–6.CrossRefGoogle Scholar
  30. 30.
    Calle EE. Obesity and cancer. BMJ 2007;335:1107–8.CrossRefGoogle Scholar
  31. 31.
    Gómez-Ambrosi J, Frühbeck G. Unlocking the molecular basis of obesity. Future Lipidol. 2007;2:577–81.CrossRefGoogle Scholar
  32. 32.
    Chan CM, Lykkesfeldt AE, Parker MG, et al. Expression of nuclear receptor interacting proteins TIF-1, SUG-1, receptor interacting protein 140, and corepressor SMRT in tamoxifen-resistant breast cancer. Clin Cancer Res. 1999;5:3460–7.PubMedGoogle Scholar
  33. 33.
    Rey JM, Pujol P, Callier P, et al. Semiquantitative reverse transcription-polymerase chain reaction to evaluate the expression patterns of genes involved in the oestrogen pathway. J Mol Endocrinol. 2000;24:433–40.CrossRefGoogle Scholar
  34. 34.
    Mostaqul Huq MD, Gupta P, Wei LN. Post-translational modifications of nuclear co-repressor RIP140: a therapeutic target for metabolic diseases. Curr Med Chem. 2008;15:386–92.CrossRefGoogle Scholar
  35. 35.
    Rytinki MM, Palvimo JJ. SUMOylation modulates the transcription repressor function of RIP140. J Biol Chem. 2008;283:11586–95.CrossRefGoogle Scholar
  36. 36.
    Berriel Diaz M, Krones-Herzig A, Metzger D, et al. Nuclear receptor cofactor receptor interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice. Hepatology 2008;48:782–91.CrossRefGoogle Scholar
  37. 37.
    Marceau P. Contribution of bariatric surgery to the comprehension of morbid obesity. Obes Surg. 2005;15:3–10.CrossRefGoogle Scholar
  38. 38.
    Froidevaux F, Schutz Y, Christin L, et al. Energy expenditure in obese women before and during weight loss, after refeeding, and in the weight-relapse period. Am J Clin Nutr. 1993;57:35–42.CrossRefGoogle Scholar
  39. 39.
    Leibel RL, Rosenbaum M, Hirsch J. Changes in energy expenditure resulting from altered body weight. N Engl J Med. 1995;332:621–8.CrossRefGoogle Scholar
  40. 40.
    Rosenbaum M, Hirsch J, Gallagher DA, et al. Long-term persistence of adaptive thermogenesis in subjects who have maintained a reduced body weight. Am J Clin Nutr. 2008;88:906–12.CrossRefGoogle Scholar
  41. 41.
    Adami GF, Compostano A, Bessarione D, et al. Resting energy expenditure in long-term postobese subjects after weight normalization by dieting or biliopancreatic diversion. Obes Surg. 1993;3:397–9.CrossRefGoogle Scholar
  42. 42.
    Nadreau E, Baraboi ED, Samson P, et al. Effects of the biliopancreatic diversion on energy balance in the rat. Int J Obes. 2006;30:419–29.CrossRefGoogle Scholar
  43. 43.
    Mendieta-Zeron H, Larrad-Jimenez A, Frühbeck G, et al. Larrad biliopancreatic diversion in Sprague–Dawley rats. Analysis of weight loss related to food intake. Obes Surg. 2009;19:484–9Google Scholar
  44. 44.
    Zschiedrich I, Hardeland U, Krones-Herzig A, et al. Coactivator function of RIP140 for NFκB/RelA-dependent cytokine gene expression. Blood 2008;112:264–76.CrossRefGoogle Scholar

Copyright information

© Springer Science + Business Media, LLC 2009

Authors and Affiliations

  • Victoria Catalán
    • 1
    • 5
  • Javier Gómez-Ambrosi
    • 1
    • 5
  • Amaia Lizanzu
    • 1
  • Amaia Rodríguez
    • 1
    • 5
  • Camilo Silva
    • 2
    • 5
  • Fernando Rotellar
    • 3
    • 5
  • María J. Gil
    • 4
    • 5
  • Javier A. Cienfuegos
    • 3
    • 5
  • Javier Salvador
    • 2
    • 5
  • Gema Frühbeck
    • 1
    • 2
    • 5
    Email author
  1. 1.Metabolic Research LaboratoryClínica Universitaria de Navarra, University of NavarraPamplonaSpain
  2. 2.Department of EndocrinologyClínica Universitaria de Navarra, University of NavarraPamplonaSpain
  3. 3.Department of SurgeryClínica Universitaria de Navarra, University of NavarraPamplonaSpain
  4. 4.Department of BiochemistryClínica Universitaria de Navarra, University of NavarraPamplonaSpain
  5. 5.CIBER de Fisiopatología de la Obesidad y NutriciónInstituto de Salud Carlos IIIPamplonaSpain

Personalised recommendations