Original Article

Animal Models

Green tea reduces body fat via upregulation of neprilysin

  • International Journal of Obesity volume 40, pages 18501855 (2016)
  • doi:10.1038/ijo.2016.172
  • Download Citation
Received:
Revised:
Accepted:
Published online:

Abstract

Background/Objective:

Consumption of green tea has become increasingly popular, particularly because of claimed reduction in body weight. We recently reported that animals with pharmacological inhibition (by candoxatril) or genetic absence of the endopeptidase neprilysin (NEP) develop an obese phenotype. We now investigated the effect of green tea extract (in drinking water) on body weight and body composition and the mediating role of NEP.

Subjects/Methods:

To elucidate the role of NEP in mediating the beneficial effects of green tea extract, ‘Berlin fat mice’ or NEP-deficient mice and their age- and gender-matched wild-type controls received the extract in two different doses (300 or 600 mg kg−1 body weight per day) in the drinking water.

Results:

In ‘Berlin fat mice’, 51 days of green tea treatment did not only prevent fat accumulation (control: day 0: 30.5% fat, day 51: 33.1%; NS) but also reduced significant body fat (green tea: day 0: 27.8%, day 51: 20.9%, P<0.01) and body weight below the initial levels. Green tea reduced food intake. This was paralleled by a selective increase in peripheral (in kidney 17%, in intestine 92%), but not central NEP expression and activity, leading to downregulation of orexigens (like galanin and neuropeptide Y (NPY)) known to be physiological substrates of NEP. Consequently, in NEP-knockout mice, green tea extract failed to reduce body fat/weight.

Conclusions:

Our data generate experimental proof for the assumed effects of green tea on body weight and the key role for NEP in such process, and thus open a new avenue for the treatment of obesity.

  • Subscribe to International Journal of Obesity for full access:

    $652

    Subscribe

Additional access options:

Already a subscriber?  Log in  now or  Register  for online access.

References

  1. 1.

    . Will green tea be even better than black tea to increase coronary flow velocity reserve? Am J Cardiol 2004; 94: 1223.

  2. 2.

    , . Mechanistic issues concerning cancer prevention by tea catechins. Mol Nutr Food Res 2011; 55: 819–831.

  3. 3.

    , , . Tea and cancer prevention: epidemiological studies. Pharmacol Res 2011; 64: 123–135.

  4. 4.

    , , , , , et al. Efficacy of a green tea extract rich in catechin polyphenols and caffeine in increasing 24-h energy expenditure and fat oxidation in humans. Am J Clin Nutr 1999; 70: 1040–1045.

  5. 5.

    , , , , . The obesity pandemic: where have we been and where are we going? Obesity Res 2004; 12: 88–101.

  6. 6.

    NHS - The Information Centre Statistics on Obesity, Physical Activity and Diet: England, January 2008. In: NHS - The Information Centre (ed) NHS - The Information Centre. The Information Centre: London, 2008, p 222.

  7. 7.

    , , . The genetics of human obesity. Nat. Rev. Genet. 2005; 6: 221–234.

  8. 8.

    , , , , , et al. New function for an old enzyme: NEP deficient mice develop late-onset obesity. PloS One 2010; 5: e12793.

  9. 9.

    , , , , , . Structural substrate conditions required for neutral endopeptidase-mediated natriuretic peptide degradation. J Mol Biol 2009; 393: 496–503.

  10. 10.

    , . Neutral endopeptidase and angiotensin-converting enzyme – key enzymes terminating the action of neuroendocrine mediators. Exp Dermatol 2004; 13: 22–26.

  11. 11.

    , , , , , et al. Improved learning and memory in aged mice deficient in amyloid beta-degrading neutral endopeptidase. PloS One 2009; 4: e4590.

  12. 12.

    , . Enhancement of neutral endopeptidase activity in SK-N-SH cells by green tea extract. Phytomedicine 2003; 10: 494–498.

  13. 13.

    , , , . Epigallocatechin gallate attenuates diet-induced obesity in mice by decreasing energy absorption and increasing fat oxidation. Int J Obesity 2005; 29: 615–623.

  14. 14.

    , , , , . Exercise and green tea extract stimulate fat oxidation and prevent obesity in mice. Med Sci Sports Exerc 2005; 37: 1884–1892.

  15. 15.

    , , , , , et al. Neutral endopeptidase modulation of septic shock. J Exp Med 1995; 181: 2271–2275.

  16. 16.

    , , , , , . Genetic, sex, and diet effects on body weight and obesity in the Berlin Fat Mouse Inbred lines. Physiol Genomics 2006; 27: 264–270.

  17. 17.

    , , , , , et al. Inhibitory activity of a green tea extract and some of its constituents on multidrug resistance-associated protein 2 functionality. Planta Med 2005; 71: 135–141.

  18. 18.

    , , , , , . Lack of angiotensin II conversion to angiotensin III increases water but not alcohol consumption in aminopeptidase A-deficient mice. Regul Pept 2006; 136: 130–137.

  19. 19.

    , . Induction of neutral endopeptidase (NEP) activity of SK-N-SH cells by natural compounds from green tea. J Pharm Pharmacol 2006; 58: 495–501.

  20. 20.

    , , , , , et al. The vasopeptidase inhibitor AVE7688 ameliorates type 2 diabetic nephropathy. Diabetologia 2004; 47: 98–103.

  21. 21.

    , , , , . Acute effects of epigallocatechin gallate from green tea on oxidation and tissue incorporation of dietary lipids in mice fed a high-fat diet. Int J Obesity 2012; 36: 735–743.

  22. 22.

    , . Metabolism and functions of neuropeptide Y. Neurochem Res 1996; 21: 1125–1132.

  23. 23.

    , , , . Feeding behaviour in galanin knockout mice supports a role of galanin in fat intake and preference. J Neuroendocrinol 2008; 20: 199–206.

  24. 24.

    , , , , , et al. A neuropeptide Y Y5 antagonist selectively ameliorates body weight gain and associated parameters in diet-induced obese mice. Proc Natl Acad Sci USA 2006; 103: 7154–7158.

  25. 25.

    , , , , , et al. Neuropeptide Y5 receptor antagonism does not induce clinically meaningful weight loss in overweight and obese adults. Cell Metab 2006; 4: 275–282.

Download references

Acknowledgements

The research has been supported by grants from the Deutsche Forschungsgemeinschaft (DFG; WA1441/18-1, SI483/8-1; WA1441/18-2, SI483/8-2). The authors thank Frutarom for providing the green tea extract free of charge. Furthermore, the intense discussions with Professor Stephen Atkin (Hull York Medical School) and the technical support by Esther-Pia Jansen, Bettina Kahlich, and Stephanie Führl are greatly appreciated.

Author information

Author notes

    • M Muenzner
    •  & N Tappenbeck

    These authors contributed equally to this work

Affiliations

  1. Leibnizinstitut für Molekulare Pharmakologie (FMP), Berlin, Germany

    • M Muenzner
    • , R Rülke
    • , J Furkert
    •  & W-E Siems
  2. Department Cardiac Pathobiology, Excellence Cluster Cardio-Pulmonary System, Justus-Liebig-Universität, Gießen, Germany

    • N Tappenbeck
    •  & F Gembardt
  3. Medical Faculty Mannheim, University Heidelberg, Institute of Experimental and Clinical Pharmacology and Toxicology, Mannheim, Germany

    • N Tappenbeck
    •  & T Walther
  4. Department of Internal Medicine III – Division of Nephrology, University Hospital Carl Gustav Carus at the Technische Universität Dresden, Dresden, Germany

    • F Gembardt
  5. Institut für Pharmazie/Dahlem, Centre of Plant Sciences (DCPS), Freie Universität Berlin, Berlin, Germany

    • M F Melzig
  6. Department for Crop and Animal Sciences, Animal Breeding and Molecular Genetics, Humboldt-Universität Berlin, Berlin, Germany

    • G A Brockmann
  7. Department of Obstetrics and Clinic of Paediatric Surgery, University Leipzig, Leipzig, Germany

    • T Walther
  8. Department of Pharmacology and Therapeutics, School of Medicine and School of Pharmacy, University College Cork, Cork, Ireland

    • T Walther

Authors

  1. Search for M Muenzner in:

  2. Search for N Tappenbeck in:

  3. Search for F Gembardt in:

  4. Search for R Rülke in:

  5. Search for J Furkert in:

  6. Search for M F Melzig in:

  7. Search for W-E Siems in:

  8. Search for G A Brockmann in:

  9. Search for T Walther in:

Competing interests

The authors declare no conflict of interest.

Corresponding author

Correspondence to T Walther.