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Hochfettdiät induziert molekulare und physiologische Dysfunktionen der Harnblase

High fat diet-induced molecular and physiological dysfunction of the urinary bladder

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Zusammenfassung

Hintergrund

Adipositas ist mit seiner Vielzahl an Komorbiditäten zur weltweiten Pandemie angewachsen. Der vorliegende Beitrag behandelt pathophysiologische Aspekte der adipositasassoziierten Harnblasendysfunktionen.

Material und Methoden

Unsere Ergebnisse beruhen auf zahlreichen In-vitro- und In-vivo-Experimenten inklusive eines Hochfettdiät- (HFD)-Rattenmodells und sind in den angegebenen Publikationen detailliert beschrieben.

Ergebnisse

In kultivierten humanen Detrusormyozyten wurden adipositasassoziierte pathophysiologische Mechanismen direkt durch die gesättigte freie Fettsäure Palmitat induziert. Im Rattenmodell bewirkte HFD eine starke Fibrosierung der Harnblasenwand und eine Herunterregulation des muskarinischen M3-Rezeptors, was zu einer verminderten Kontraktilität der Harnblase führte. Die Fibrosierung war nach bariatrisch-chirurgischer Intervention (Sleeve-Gastrektomie) regredient.

Schlussfolgerung

Unsere Ergebnisse unterstreichen die Bedeutung der Adipositas für urologische Funktionsstörungen. Angesichts der epidemiologischen Dimension der Adipositas mit stetig steigenden Fallzahlen ist eine Neubewertung dieser pathologischen Kondition in der Urologie notwendig.

Abstract

Background

Obesity with its multiple comorbidities has become a global pandemia. We here report on the pathophysiological aspects of obesity-associated urinary bladder dysfunctions.

Material and methods

Our results are based on multiple in vitro and in vivo studies including a high fat diet (HFD) rat animal model of which the details are given in the cited publications.

Results

In cultured human detrusor muscle cells, obesity-related pathophysiological mechanisms were directly induced by the saturated free fatty acid palmitate. In HFD animals, we found serious fibrosis of the bladder wall and downregulation of the muscarinic M3-receptor leading to diminished contractility of the urinary bladder. Bariatric surgical intervention (sleeve gastrectomy) reversed the fibrosis.

Conclusion

Our results support the relevance of obesity for urological bladder dysfunction. The epidemic dimension of obesity with its steadily growing number of cases requires a re-evaluation of this pathological condition in the urological context.

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Literatur

  1. Bhadoria AS, Kasar PK, Toppo NA et al (2014) Prevalence of hypertension and associated cardiovascular risk factors in Central India. J Family Community Med 21:29–38

    Article  PubMed Central  PubMed  Google Scholar 

  2. Bonnefond C, Clement M (2014) Social class and body weight among Chinese urban adults: the role of the middle classes in the nutrition transition. Soc Sci Med 112:22–29

    Article  PubMed  Google Scholar 

  3. Braverman AS, Tibb AS, Ruggieri MRS (2006) M2 and M3 muscarinic receptor activation of urinary bladder contractile signal transduction. I. Normal rat bladder. J Pharmacol Exp Ther 316:869–874

    Article  CAS  PubMed  Google Scholar 

  4. Daneshgari F, Liu G, Birder L et al (2009) Diabetic bladder dysfunction: current translational knowledge. J Urol 182:S18–S26

    Article  CAS  PubMed  Google Scholar 

  5. Daneshgari F, Moore C (2006) Diabetic uropathy. Semin Nephrol 26:182–185

    Article  PubMed  Google Scholar 

  6. Ebbesen MH, Hunskaar S, Rortveit G et al (2013) Prevalence, incidence and remission of urinary incontinence in women: longitudinal data from the Norwegian HUNT study (EPINCONT). BMC Urol 13:27

    Article  PubMed Central  PubMed  Google Scholar 

  7. Elia G, Dye TD, Scariati PD (2001) Body mass index and urinary symptoms in women. Int Urogynecol J Pelvic Floor Dysfunct 12:366–369

    Article  CAS  PubMed  Google Scholar 

  8. Gasbarro G, Lin DL, Vurbic D et al (2010) Voiding function in obese and type 2 diabetic female rats. Am J Physiol Renal Physiol 298:72–77

    Article  Google Scholar 

  9. Heinrich M, Oberbach A, Schlichting N et al (2011) Cytokine effects on gap junction communication and connexin expression in human bladder smooth muscle cells and suburothelial myofibroblasts. PLoS One 6:20792

    Article  Google Scholar 

  10. Hunskaar S (2008) A systematic review of overweight and obesity as risk factors and targets for clinical intervention for urinary incontinence in women. Neurourol Urodyn 27:749–757

    Article  PubMed  Google Scholar 

  11. Kirschner-Hermanns R, Daneshgari F, Vahabi B et al (2012) Does diabetes mellitus-induced bladder remodeling affect lower urinary tract function? ICI-RS 2011. Neurourol Urodyn 31:359–364

    Article  PubMed  Google Scholar 

  12. Lee WC, Chiang PH, Tain YL et al (2012) Sensory dysfunction of bladder mucosa and bladder oversensitivity in a rat model of metabolic syndrome. PLoS One 7:45578

    Article  Google Scholar 

  13. Melin I, Falconer C, Rossner S et al (2007) Nocturia and overactive bladder in obese women: a case-control study. Obes Res Clin Pract 1:I–II

    Article  PubMed  Google Scholar 

  14. Moschen AR, Molnar C, Geiger S et al (2010) Anti-inflammatory effects of excessive weight loss: potent suppression of adipose interleukin 6 and tumour necrosis factor alpha expression. Gut 59:1259–1264

    Article  CAS  PubMed  Google Scholar 

  15. Neuhaus J, Schlichting N, Oberbach A et al (2007) Lipopolysaccharide-mediated regulation of interleukin-6 in cultured human detrusor smooth muscle cells. Urologe A 46:1193–1197

    Article  CAS  PubMed  Google Scholar 

  16. Neuman M, Kawachi I, Gortmaker S et al (2013) Urban-rural differences in BMI in low- and middle-income countries: the role of socioeconomic status. Am J Clin Nutr 97:428–436

    Article  CAS  PubMed Central  PubMed  Google Scholar 

  17. Ng M, Fleming T, Robinson M et al (2014) Global, regional, and national prevalence of overweight and obesity in children and adults during 1980–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet 384(9945):766–781

    Article  PubMed  Google Scholar 

  18. Noria SF, Grantcharov T (2013) Biological effects of bariatric surgery on obesity-related comorbidities. Can J Surg 56:47–57

    Article  PubMed Central  PubMed  Google Scholar 

  19. Oberbach A, Neuhaus J, Schlichting N et al (2013) Sleeve gastrectomy reduces xanthine oxidase and uric acid in a rat model of morbid obesity. Surg Obes Relat Dis 56(7):1623–1628

    Google Scholar 

  20. Oberbach A, Schlichting N, Bluher M et al (2010) Palmitate induced IL-6 and MCP-1 expression in human bladder smooth muscle cells provides a link between diabetes and urinary tract infections. PLoS One 5:10882

    Article  Google Scholar 

  21. Oberbach A, Schlichting N, Heinrich M et al (2013) Weight loss surgery improves the metabolic status in an obese rat model but does not affect bladder fibrosis associated with high fat diet feeding. Int J Obes (Lond) 38(8):1061–1017. doi: 10.1038/ijo.2013.199

    Google Scholar 

  22. Oberbach A, Jehmlich N, Schlichting N et al (2013) Molecular fingerprint of high fat diet induced urinary bladder metabolic dysfunction in a rat model. PLoS One 8:66636

    Article  Google Scholar 

  23. Oberbach A, Schlichting N, Heinrich M et al (2012) Free fatty acid palmitate impairs the vitality and function of cultured human bladder smooth muscle cells. PLoS One 7:41026

    Article  Google Scholar 

  24. Poirier P, Giles TD, Bray GA et al (2006) Obesity and cardiovascular disease: pathophysiology, evaluation, and effect of weight loss: an update of the 1997 American Heart Association Scientific Statement on Obesity and Heart Disease from the Obesity Committee of the Council on Nutrition, Physical Activity, and Metabolism. Circulation 113:898–918

    Article  PubMed  Google Scholar 

  25. Samjoo IA, Safdar A, Hamadeh MJ et al (2013) The effect of endurance exercise on both skeletal muscle and systemic oxidative stress in previously sedentary obese men. Nutr Diabetes 3:88

    Article  Google Scholar 

  26. Semins MJ, Shore AD, Makary MA et al (2012) The impact of obesity on urinary tract infection risk. Urology 79:266–269

    Article  PubMed  Google Scholar 

  27. Staiger H, Staiger K, Stefan N et al (2004) Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells. Diabetes 53:3209–3216

    Article  CAS  PubMed  Google Scholar 

  28. Weigert C, Brodbeck K, Staiger H et al (2004) Palmitate, but not unsaturated fatty acids, induces the expression of interleukin-6 in human myotubes through proteasome-dependent activation of nuclear factor-kappaB. J Biol Chem 279:23942–23952

    Article  CAS  PubMed  Google Scholar 

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Einhaltung ethischer Richtlinien

Interessenkonflikt. A. Oberbach, N. Schlichting, M. Heinrich, Y. Kullnick, S. Lehmann, V. Adams, J.-U. Stolzenburg und J. Neuhaus geben an, dass kein Interessenkonflikt besteht. Alle im vorliegenden Manuskript beschriebenen Untersuchungen am Menschen wurden mit Zustimmung der zuständigen Ethik-Kommission, im Einklang mit nationalem Recht sowie gemäß der Deklaration von Helsinki von 1975 (in der aktuellen, überarbeiteten Fassung) durchgeführt. Von allen beteiligten Patienten liegt eine Einverständniserklärung vor. Alle nationalen Richtlinien zur Haltung und zum Umgang mit Labortieren wurden eingehalten und die notwendigen Zustimmungen der zuständigen Behörden liegen vor.

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Authors and Affiliations

  1. Klinik für Herzchirurgie, Herzzentrum Leipzig, Leipzig, Deutschland

    A. Oberbach, M. Heinrich & Y. Kullnick

  2. Klinik und Poliklinik für Kinderchirurgie, Universität Leipzig, Leipzig, Deutschland

    N. Schlichting

  3. Integriertes Forschungs- und Behandlungszentrum Adipositas, Universität Leipzig, Leipzig, Deutschland

    S. Lehmann

  4. Klinik für Innere Medizin/Kardiologie, Herzzentrum Leipzig, Leipzig, Deutschland

    V. Adams

  5. Klinik und Poliklinik für Urologie, Department für Operative Medizin, Universitätsklinikum Leipzig AöR, Liebigstraße 20, 04103, Leipzig, Deutschland

    J.-W. Stolzenburg &  J. Neuhaus

Authors
  1. A. Oberbach
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  2. N. Schlichting
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  3. M. Heinrich
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  4. Y. Kullnick
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  5. S. Lehmann
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  6. V. Adams
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  7. J.-W. Stolzenburg
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  8. J. Neuhaus
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Corresponding author

Correspondence to J. Neuhaus.

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Oberbach, A., Schlichting, N., Heinrich, M. et al. Hochfettdiät induziert molekulare und physiologische Dysfunktionen der Harnblase. Urologe 53, 1805–1811 (2014). https://doi.org/10.1007/s00120-014-3659-1

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  • DOI: https://doi.org/10.1007/s00120-014-3659-1

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