Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Article
  • Published:

An AMP-activated protein kinase–stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice

Nature Medicine volume 22, pages 1120–1130 (2016)Cite this article

Subjects

Abstract

Cachexia represents a fatal energy-wasting syndrome in a large number of patients with cancer that mostly results in a pathological loss of skeletal muscle and adipose tissue. Here we show that tumor cell exposure and tumor growth in mice triggered a futile energy-wasting cycle in cultured white adipocytes and white adipose tissue (WAT), respectively. Although uncoupling protein 1 (Ucp1)-dependent thermogenesis was dispensable for tumor-induced body wasting, WAT from cachectic mice and tumor-cell-supernatant-treated adipocytes were consistently characterized by the simultaneous induction of both lipolytic and lipogenic pathways. Paradoxically, this was accompanied by an inactivated AMP-activated protein kinase (Ampk), which is normally activated in peripheral tissues during states of low cellular energy. Ampk inactivation correlated with its degradation and with upregulation of the Ampk-interacting protein Cidea. Therefore, we developed an Ampk-stabilizing peptide, ACIP, which was able to ameliorate WAT wasting in vitro and in vivo by shielding the Cidea-targeted interaction surface on Ampk. Thus, our data establish the Ucp1-independent remodeling of adipocyte lipid homeostasis as a key event in tumor-induced WAT wasting, and we propose the ACIP-dependent preservation of Ampk integrity in the WAT as a concept in future therapies for cachexia.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1: Tumor cell exposure induces lipolysis, lipogenesis and energy crisis in adipocytes.
Figure 2: Diminished Ampk activity in iWAT is a key feature of various mouse models of cancer cachexia.
Figure 3: WAT loss in cancer cachexia is not mediated by Ucp1.
Figure 4: Cidea mediates disruption of Ampk integrity.
Figure 5: CIDEA expression is higher in human WAT under conditions of substantial weight loss.
Figure 6: ACIP treatment reduces WAT wasting in cachexia.

Similar content being viewed by others

Accession codes

Primary accessions

Gene Expression Omnibus

Referenced accessions

Gene Expression Omnibus

References

  1. Fearon, K.C., Glass, D.J. & Guttridge, D.C. Cancer cachexia: mediators, signaling and metabolic pathways. Cell Metab. 16, 153–166 (2012).

    Article  CAS  PubMed  Google Scholar 

  2. Dewys, W.D. et al. Prognostic effect of weight loss prior to chemotherapy in cancer patients. Am. J. Med. 69, 491–497 (1980).

    Article  CAS  PubMed  Google Scholar 

  3. Mondello, P. et al. Cancer cachexia syndrome: pathogenesis, diagnosis and new therapeutic options. Nutr. Cancer 67, 12–26 (2015).

    Article  CAS  PubMed  Google Scholar 

  4. Theologides, A. Cancer cachexia. Cancer 43 (Suppl.), 2004–2012 (1979).

    Article  CAS  PubMed  Google Scholar 

  5. Jones, A. et al. TSC22D4 is a molecular output of hepatic wasting metabolism. EMBO Mol. Med. 5, 294–308 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  6. Schäfer, M. et al. Ataxin-10 is part of a cachexokine cocktail triggering cardiac metabolic dysfunction in cancer cachexia. Mol. Metab. 5, 67–78 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  7. Yu, Y.H. & Ginsberg, H.N. Adipocyte signaling and lipid homeostasis: sequelae of insulin-resistant adipose tissue. Circ. Res. 96, 1042–1052 (2005).

    Article  CAS  PubMed  Google Scholar 

  8. Agustsson, T. et al. Mechanism of increased lipolysis in cancer cachexia. Cancer Res. 67, 5531–5537 (2007).

    Article  CAS  PubMed  Google Scholar 

  9. Batista, M.L. Jr. et al. Adipose-tissue-derived factors as potential biomarkers in cachectic cancer patients. Cytokine 61, 532–539 (2013).

    Article  CAS  PubMed  Google Scholar 

  10. Pausch, T. et al. Cachexia but not obesity worsens the postoperative outcome after pancreatoduodenectomy in pancreatic cancer. Surgery 152, S81–S88 (2012).

    Article  PubMed  Google Scholar 

  11. Di Sebastiano, K.M. et al. Accelerated muscle and adipose tissue loss may predict survival in pancreatic cancer patients: the relationship with diabetes and anemia. Br. J. Nutr. 109, 302–312 (2013).

    Article  CAS  PubMed  Google Scholar 

  12. Petruzzelli, M. et al. A switch from white to brown fat increases energy expenditure in cancer-associated cachexia. Cell Metab. 20, 433–447 (2014).

    Article  CAS  PubMed  Google Scholar 

  13. Kir, S. et al. Tumor-derived PTH-related protein triggers adipose tissue browning and cancer cachexia. Nature 513, 100–104 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. Xu, L., Zhou, L. & Li, P. CIDE proteins and lipid metabolism. Arterioscler. Thromb. Vasc. Biol. 32, 1094–1098 (2012).

    Article  CAS  PubMed  Google Scholar 

  15. Zhou, Z. et al. Cidea-deficient mice have lean phenotype and are resistant to obesity. Nat. Genet. 35, 49–56 (2003).

    Article  CAS  PubMed  Google Scholar 

  16. Laurencikiene, J. et al. Evidence for an important role of CIDEA in human cancer cachexia. Cancer Res. 68, 9247–9254 (2008).

    Article  CAS  PubMed  Google Scholar 

  17. Blum, D. et al. Cancer cachexia: a systematic literature review of items and domains associated with involuntary weight loss in cancer. Crit. Rev. Oncol. Hematol. 80, 114–144 (2011).

    Article  PubMed  Google Scholar 

  18. Hardie, D.G., Ross, F.A. & Hawley, S.A. AMPK: a nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251–262 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  19. Dzamko, N. et al. AMPK-β1 deletion reduces appetite, preventing obesity and hepatic insulin resistance. J. Biol. Chem. 285, 115–122 (2010).

    Article  CAS  PubMed  Google Scholar 

  20. Gaidhu, M.P., Bikopoulos, G. & Ceddia, R.B. Chronic AICAR-induced AMP-kinase activation regulates adipocyte lipolysis in a time-dependent and fat-depot-specific manner in rats. Am. J. Physiol. Cell Physiol. 303, C1192–C1197 (2012).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  21. Gaidhu, M.P. et al. Prolonged AICAR-induced AMP kinase activation promotes energy dissipation in white adipocytes: novel mechanisms integrating HSL and ATGL. J. Lipid Res. 50, 704–715 (2009).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  22. Anthony, N.M., Gaidhu, M.P. & Ceddia, R.B. Regulation of visceral and subcutaneous adipocyte lipolysis by acute AICAR-induced AMPK activation. Obesity (Silver Spring) 17, 1312–1317 (2009).

    CAS  Google Scholar 

  23. Boon, H. et al. Intravenous AICAR administration reduces hepatic glucose output and inhibits whole-body lipolysis in type 2 diabetic patients. Diabetologia 51, 1893–1900 (2008).

    Article  CAS  PubMed  Google Scholar 

  24. Bourron, O. et al. Biguanides and thiazolidinediones inhibit stimulated lipolysis in human adipocytes through activation of AMP-activated protein kinase. Diabetologia 53, 768–778 (2010).

    Article  CAS  PubMed  Google Scholar 

  25. Fearon, K. et al. Definition and classification of cancer cachexia: an international consensus. Lancet Oncol. 12, 489–495 (2011).

    Article  PubMed  Google Scholar 

  26. Tanaka, Y. et al. Experimental cancer cachexia induced by transplantable colon 26 adenocarcinoma in mice. Cancer Res. 50, 2290–2295 (1990).

    CAS  PubMed  Google Scholar 

  27. Sherry, B.A. et al. Anticachectin and tumor necrosis factor–α antibodies attenuate development of cachexia in tumor models. FASEB J. 3, 1956–1962 (1989).

    Article  CAS  PubMed  Google Scholar 

  28. Nowakowska, M., Pospiech, K., Lewandowska, U., Piastowska-Ciesielska, A.W. & Bednarek, A.K. Diverse effect of WWOX overexpression in HT29 and SW480 colon cancer cell lines. Tumour Biol. 35, 9291–9301 (2014).

    Article  CAS  PubMed  Google Scholar 

  29. Rosenberg, S.A., Spiess, P. & Lafreniere, R. A new approach to the adoptive immunotherapy of cancer with tumor-infiltrating lymphocytes. Science 233, 1318–1321 (1986).

    Article  CAS  PubMed  Google Scholar 

  30. Rydén, M. et al. Lipolysis—not inflammation, cell death or lipogenesis—is involved in adipose tissue loss in cancer cachexia. Cancer 113, 1695–1704 (2008).

    Article  PubMed  Google Scholar 

  31. Daval, M. et al. Antilipolytic action of AMP-activated protein kinase in rodent adipocytes. J. Biol. Chem. 280, 25250–25257 (2005).

    Article  CAS  PubMed  Google Scholar 

  32. Fullerton, M.D. et al. Single phosphorylation sites in Acc1 and Acc2 regulate lipid homeostasis and the insulin-sensitizing effects of metformin. Nat. Med. 19, 1649–1654 (2013).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  33. Sullivan, J.E. et al. Inhibition of lipolysis and lipogenesis in isolated rat adipocytes with AICAR, a cell-permeable activator of AMP-activated protein kinase. FEBS Lett. 353, 33–36 (1994).

    Article  CAS  PubMed  Google Scholar 

  34. Djouder, N. et al. PKA phosphorylates and inactivates AMPK-α to promote efficient lipolysis. EMBO J. 29, 469–481 (2010).

    Article  CAS  PubMed  Google Scholar 

  35. Berriel Diaz, M. et al. Nuclear receptor cofactor receptor–interacting protein 140 controls hepatic triglyceride metabolism during wasting in mice. Hepatology 48, 782–791 (2008).

    Article  CAS  PubMed  Google Scholar 

  36. Das, S.K. et al. Adipose triglyceride lipase contributes to cancer-associated cachexia. Science 333, 233–238 (2011).

    Article  CAS  PubMed  Google Scholar 

  37. Thureson-Klein, A., Lagercrantz, H. & Barnard, T. Chemical sympathectomy of interscapular brown adipose tissue. Acta Physiol. Scand. 98, 8–18 (1976).

    Article  CAS  PubMed  Google Scholar 

  38. Kuraguchi, M. et al. Adenomatous polyposis coli (APC) is required for normal development of skin and thymus. PLoS Genet. 2, e146 (2006).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. Tschöp, M.H. et al. A guide to analysis of mouse energy metabolism. Nat. Methods 9, 57–63 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. Vegiopoulos, A. et al. Cyclooxygenase-2 controls energy homeostasis in mice by de novo recruitment of brown adipocytes. Science 328, 1158–1161 (2010).

    Article  CAS  PubMed  Google Scholar 

  41. Enerbäck, S. et al. Mice lacking mitochondrial uncoupling protein are cold-sensitive but not obese. Nature 387, 90–94 (1997).

    Article  PubMed  Google Scholar 

  42. Qi, J. et al. Downregulation of AMP-activated protein kinase by Cidea-mediated ubiquitination and degradation in brown adipose tissue. EMBO J. 27, 1537–1548 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  43. Nordström, E.A. et al. A human-specific role of cell-death-inducing DFFA (DNA fragmentation factor–α)-like effector A (CIDEA) in adipocyte lipolysis and obesity. Diabetes 54, 1726–1734 (2005).

    Article  PubMed  Google Scholar 

  44. Kumar, N.B. et al. Cancer cachexia: traditional therapies and novel molecular-mechanism-based approaches to treatment. Curr. Treat. Options Oncol. 11, 107–117 (2010).

    Article  PubMed  PubMed Central  Google Scholar 

  45. Lainscak, M., Filippatos, G.S., Gheorghiade, M., Fonarow, G.C. & Anker, S.D. Cachexia: common, deadly, with an urgent need for precise definition and new therapies. Am. J. Cardiol. 101 11A, 8E–10E (2008).

    Article  PubMed  Google Scholar 

  46. Jatoi, A. et al. A placebo-controlled, double-blind trial of infliximab for cancer-associated weight loss in elderly and/or poor performance non-small-cell lung cancer patients (N01C9). Lung Cancer 68, 234–239 (2010).

    Article  PubMed  Google Scholar 

  47. Tsoli, M. et al. Depletion of white adipose tissue in cancer cachexia syndrome is associated with inflammatory signaling and disrupted circadian regulation. PLoS One 9, e92966 (2014).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. de Vos-Geelen, J., Fearon, K.C. & Schols, A.M. The energy balance in cancer cachexia revisited. Curr. Opin. Clin. Nutr. Metab. Care 17, 509–514 (2014).

    Article  PubMed  Google Scholar 

  49. Gauthier, M.S. et al. AMP-activated protein kinase is activated as a consequence of lipolysis in the adipocyte: potential mechanism and physiological relevance. J. Biol. Chem. 283, 16514–16524 (2008).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  50. Vaughan, M. The production and release of glycerol by adipose tissue incubated in vitro. J. Biol. Chem. 237, 3354–3358 (1962).

    CAS  PubMed  Google Scholar 

  51. Klein, S. & Wolfe, R.R. Whole-body lipolysis and triglyceride–fatty acid cycling in cachectic patients with esophageal cancer. J. Clin. Invest. 86, 1403–1408 (1990).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  52. Tsoli, M., Swarbrick, M.M. & Robertson, G.R. Lipolytic and thermogenic depletion of adipose tissue in cancer cachexia. Semin. Cell Dev. Biol. 54, 68–81 (2016).

    Article  CAS  PubMed  Google Scholar 

  53. Wang, Z. et al. Homocysteine suppresses lipolysis in adipocytes by activating the AMPK pathway. Am. J. Physiol. Endocrinol. Metab. 301, E703–E712 (2011).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  54. Deminice, R. et al. Creatine supplementation prevents hyperhomocysteinemia, oxidative stress and cancer-induced cachexia progression in Walker-256 tumor-bearing rats. Amino Acids http://dx.doi.org/10.1007/s00726-016-2172-9 (2016).

  55. Diao, L. et al. Alternative mechanism for white adipose tissue lipolysis after thermal injury. Mol. Med. 21, 959 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  56. Steinberg, G.R. et al. Tumor-necrosis-factor-α-induced skeletal muscle insulin resistance involves suppression of AMP kinase signaling. Cell Metab. 4, 465–474 (2006).

    Article  CAS  PubMed  Google Scholar 

  57. Livak, K.J. & Schmittgen, T.D. Analysis of relative gene expression data using real-time quantitative PCR and the 2−ΔΔCt method. Methods 25, 402–408 (2001).

    Article  CAS  PubMed  Google Scholar 

  58. Rodeheffer, M.S., Birsoy, K. & Friedman, J.M. Identification of white adipocyte progenitor cells in vivo. Cell 135, 240–249 (2008).

    Article  CAS  PubMed  Google Scholar 

  59. Rohm, M. et al. Transcriptional cofactor TBLR1 controls lipid mobilization in white adipose tissue. Cell Metab. 17, 575–585 (2013).

    Article  CAS  PubMed  Google Scholar 

  60. Jelenik, T. et al. AMP-activated protein kinase–α2 subunit is required for the preservation of hepatic insulin sensitivity by 'n – 3' polyunsaturated fatty acids. Diabetes 59, 2737–2746 (2010).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. Hardie, D.G., Salt, I.P. & Davies, S.P. Analysis of the role of the AMP-activated protein kinase in the response to cellular stress. Methods Mol. Biol. 99, 63–74 (2000).

    CAS  PubMed  Google Scholar 

  62. Dahlman, I. & Arner, P. Genetics of adipose tissue biology. Prog. Mol. Biol. Transl. Sci. 94, 39–74 (2010).

    Article  CAS  PubMed  Google Scholar 

  63. Kannt, A. et al. Association of nicotinamide-N-methyltransferase mRNA expression in human adipose tissue and the plasma concentration of its product, 1-methylnicotinamide, with insulin resistance. Diabetologia 58, 799–808 (2015).

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Acknowledgements

We would like to thank K. Müller-Decker, K. Friedrich, D. Sohn, F. Ilmberger, Y. Feuchter, B. Meissburger, M. Kirilov, A. Vegiopoulos, P. Flachs, J. Hansikova, N. Petrovic and M. Christian for helpful discussions and experimental support and D.G. Hardie (University of Dundee) for Ampk-α1-specific and Ampk-α2-specific sheep antibodies. We particularly thank T. Schafmeier for comments on the manuscript. This work was supported by grants from the Swedish Cancer Fund (P.A.), the Deutsche Forschungsgemeinschaft grant He3260/8-1 (S.H.), the European Foundation for the Study of Diabetes (S.H.), the EU FP7 project DIABAT (HEALTH-F2-2011-278373; S.H.), the DKFZ–Bayer Cooperation Program (S.H.), the HGF Cross Program Topic 'Metabolic Dysfunction' (S.H.) and the HGF 'ICEMED' Program (S.H.).

Author information

Author notes

  1. Maria Rohm and Michaela Schäfer: These authors contributed equally to this work.

Authors and Affiliations

  1. Institute for Diabetes and Cancer (IDC), Helmholtz Center Munich, Neuherberg, Germany

    Maria Rohm, Michaela Schäfer, Victor Laurent, Bilgen Ekim Üstünel, Katharina Niopek, Carolyn Algire, Oksana Hautzinger, Tjeerd P Sijmonsma, Annika Zota, Dasa Medrikova, Natalia S Pellegata, Mauricio Berriel Diaz & Stephan Herzig

  2. Joint Heidelberg–IDC Translational Diabetes Program, Inner Medicine 1, Heidelberg University Hospital, Heidelberg, Germany

    Maria Rohm, Michaela Schäfer, Victor Laurent, Bilgen Ekim Üstünel, Katharina Niopek, Carolyn Algire, Oksana Hautzinger, Tjeerd P Sijmonsma, Annika Zota, Dasa Medrikova, Natalia S Pellegata, Mauricio Berriel Diaz & Stephan Herzig

  3. Deutsches Zentrum für Diabetesforschung, Neuherberg, Germany

    Maria Rohm, Michaela Schäfer, Victor Laurent, Bilgen Ekim Üstünel, Katharina Niopek, Annika Zota, Natalia S Pellegata, Mauricio Berriel Diaz & Stephan Herzig

  4. Department of Medicine, Lipid Laboratory, Karolinska Institute, Stockholm, Sweden

    Mikael Ryden, Agné Kulyte, Ingrid Dahlman & Peter Arner

  5. Department of Molecular Biosciences, The Wenner–Gren Institute, Stockholm University, Stockholm, Sweden

    Natasa Petrovic & Barbara Cannon

  6. Université Côte d'Azur, Nice, France

    Ez-Zoubir Amri

  7. Centre National de la Recherche Scientifique (CNRS), Nice, France

    Ez-Zoubir Amri

  8. St Vincent's Institute of Medical Research, University of Melbourne, Fitzroy, Victoria, Australia

    Bruce E Kemp

  9. Mary MacKillop Institute for Health, Research Australian Catholic University, Melbourne, Victoria, Australia

    Bruce E Kemp

  10. Department of Medicine, Division of Endocrinology and Metabolism, McMaster University, Hamilton, Ontario, Canada

    Gregory R Steinberg

  11. Department of Adipose Tissue Biology, Institute of Physiology of the Academy of Sciences of the Czech Republic, Prague, Czech Republic

    Petra Janovska & Jan Kopecky

  12. Swiss Federal Institute of Technology, Institute of Food Nutrition and Health, Schwerzenbach, Switzerland

    Christian Wolfrum

  13. Department of Medicine, University of Leipzig, Leipzig, Germany

    Matthias Blüher

Authors
  1. Maria Rohm
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Michaela Schäfer
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Victor Laurent
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Bilgen Ekim Üstünel
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Katharina Niopek
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Carolyn Algire
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Oksana Hautzinger
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. Tjeerd P Sijmonsma
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. Annika Zota
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. Dasa Medrikova
    View author publications

    You can also search for this author in PubMed Google Scholar

  11. Natalia S Pellegata
    View author publications

    You can also search for this author in PubMed Google Scholar

  12. Mikael Ryden
    View author publications

    You can also search for this author in PubMed Google Scholar

  13. Agné Kulyte
    View author publications

    You can also search for this author in PubMed Google Scholar

  14. Ingrid Dahlman
    View author publications

    You can also search for this author in PubMed Google Scholar

  15. Peter Arner
    View author publications

    You can also search for this author in PubMed Google Scholar

  16. Natasa Petrovic
    View author publications

    You can also search for this author in PubMed Google Scholar

  17. Barbara Cannon
    View author publications

    You can also search for this author in PubMed Google Scholar

  18. Ez-Zoubir Amri
    View author publications

    You can also search for this author in PubMed Google Scholar

  19. Bruce E Kemp
    View author publications

    You can also search for this author in PubMed Google Scholar

  20. Gregory R Steinberg
    View author publications

    You can also search for this author in PubMed Google Scholar

  21. Petra Janovska
    View author publications

    You can also search for this author in PubMed Google Scholar

  22. Jan Kopecky
    View author publications

    You can also search for this author in PubMed Google Scholar

  23. Christian Wolfrum
    View author publications

    You can also search for this author in PubMed Google Scholar

  24. Matthias Blüher
    View author publications

    You can also search for this author in PubMed Google Scholar

  25. Mauricio Berriel Diaz
    View author publications

    You can also search for this author in PubMed Google Scholar

  26. Stephan Herzig
    View author publications

    You can also search for this author in PubMed Google Scholar

Contributions

M.Rohm, M.S., V.L., B.E.Ü., K.N., C.A., O.H., T.P.S., A.Z., D.M., N.S.P., M.Ryden, A.K., I.D., P.A., N.P., B.C., E.-Z.A., B.E.K., G.R.S., P.J., J.K., C.W., M.B. and M.B.D. performed experiments and generated experimental tools; and S.H. designed and directed the research and wrote the manuscript.

Corresponding author

Correspondence to Stephan Herzig.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–7 and Supplementary Table 1 (PDF 1072 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Rohm, M., Schäfer, M., Laurent, V. et al. An AMP-activated protein kinase–stabilizing peptide ameliorates adipose tissue wasting in cancer cachexia in mice. Nat Med 22, 1120–1130 (2016). https://doi.org/10.1038/nm.4171

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/nm.4171

This article is cited by

Search

Advanced search

Quick links

Nature Briefing: Cancer

Sign up for the Nature Briefing: Cancer newsletter — what matters in cancer research, free to your inbox weekly.

Get what matters in cancer research, free to your inbox weekly. Sign up for Nature Briefing: Cancer