Skip to main content
SpringerLink
Log in

Mouse Models of Obesity to Study the Tumor-Immune Microenvironment

  • Protocol
  • First Online:
The Tumor Microenvironment

Part of the book series: Methods in Molecular Biology ((MIMB,volume 2614))

Abstract

Obesity is associated with chronic, low-grade systemic inflammation and leads to changes in the immune microenvironment of various tissues. As a result, obesity is associated with increased risk of cancer and a worse prognosis in patients. Given the prevalence of obesity worldwide, understanding the fundamental biology governing the relationship between obesity and cancer is critical. In this chapter, we describe preclinical models of obesity that can be combined with standard tumor models and techniques to study the tumor-immune microenvironment. We also discuss important considerations when planning experiments involving these models.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Protocol
USD 49.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 129.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 169.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 249.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Calle EE, Rodriguez C, Walker-Thurmond K, Thun MJ (2003) Overweight, obesity, and mortality from cancer in a prospectively studied cohort of U.S. adults. N Engl J Med 348:1625–1638

    Article  Google Scholar 

  2. Petrelli F, Cortellini A, Indini A et al (2021) Association of obesity with survival outcomes in patients with cancer: a systematic review and meta-analysis. JAMA Netw Open 4:e213520-e

    Article  Google Scholar 

  3. Lauby-Secretan B, Scoccianti C, Loomis D et al (2016) Body fatness and Cancer—viewpoint of the IARC Working Group. N Engl J Med 375:794–798

    Article  Google Scholar 

  4. Swinburn BA, Sacks G, Hall KD et al (2011) The global obesity pandemic: shaped by global drivers and local environments. Lancet 378:804–814

    Article  Google Scholar 

  5. Hales CM, Carroll MD, Fryar CD, et al (2020) Prevalence of obesity and severe obesity among adults: United States, 2017–2018. NCHS Data Brief:1–8

    Google Scholar 

  6. Wolin KY, Carson K, Colditz GA (2010) Obesity and cancer. Oncologist 15:556–565

    Article  Google Scholar 

  7. Pischon T, Nimptsch K (2016) Obesity and risk of cancer: an introductory overview. In: Pischon T, Nimptsch K (eds) Obesity and Cancer. Springer, Cham, pp 1–15

    Chapter  Google Scholar 

  8. Stefan N, Kantartzis K, Machann J et al (2008) Identification and characterization of metabolically benign obesity in humans. Arch Intern Med 168:1609–1616

    Article  Google Scholar 

  9. Stefan N, Schick F, Häring H-U (2017) Causes, characteristics, and consequences of metabolically unhealthy normal weight in humans. Cell Metab 26:292–300

    Article  CAS  Google Scholar 

  10. Quail DF, Dannenberg AJ (2019) The obese adipose tissue microenvironment in cancer development and progression. Nat Rev Endocrinol 15:139–154

    Article  Google Scholar 

  11. Pasarica M, Sereda OR, Redman LM et al (2009) Reduced adipose tissue oxygenation in human obesity: evidence for rarefaction, macrophage chemotaxis, and inflammation without an angiogenic response. Diabetes 58:718–725

    Article  CAS  Google Scholar 

  12. Brestoff JR, Artis D (2015) Immune regulation of metabolic homeostasis in health and disease. Cell 161:146–160

    Article  CAS  Google Scholar 

  13. Vandanmagsar B, Youm Y-H, Ravussin A et al (2011) The NLRP3 inflammasome instigates obesity-induced inflammation and insulin resistance. Nat Med 17:179–188

    Article  CAS  Google Scholar 

  14. Nagareddy PR, Kraakman M, Masters SL et al (2014) Adipose tissue macrophages promote myelopoiesis and monocytosis in obesity. Cell Metab 19:821–835

    Article  CAS  Google Scholar 

  15. Kolb R, Phan L, Borcherding N et al (2016) Obesity-associated NLRC4 inflammasome activation drives breast cancer progression. Nat Commun 7:13007

    Article  CAS  Google Scholar 

  16. Arkan MC, Hevener AL, Greten FR et al (2005) IKK-β links inflammation to obesity-induced insulin resistance. Nat Med 11:191–198

    Article  CAS  Google Scholar 

  17. Solinas G, Vilcu C, Neels JG et al (2007) JNK1 in hematopoietically derived cells contributes to diet-induced inflammation and insulin resistance without affecting obesity. Cell Metab 6:386–397

    Article  CAS  Google Scholar 

  18. Hildreth AD, Ma F, Wong YY et al (2021) Single-cell sequencing of human white adipose tissue identifies new cell states in health and obesity. Nat Immunol 22:639–653

    Article  CAS  Google Scholar 

  19. Dalmas E, Rouault C, Abdennour M et al (2011) Variations in circulating inflammatory factors are related to changes in calorie and carbohydrate intakes early in the course of surgery-induced weight reduction. Am J Clin Nutr 94:450–458

    Article  CAS  Google Scholar 

  20. Nijhuis J, Rensen SS, Slaats Y et al (2009) Neutrophil activation in morbid obesity, chronic activation of acute inflammation. Obesity 17:2014–2018

    Article  CAS  Google Scholar 

  21. Quail DF, Olson OC, Bhardwaj P et al (2017) Obesity alters the lung myeloid cell landscape to enhance breast cancer metastasis through IL5 and GM-CSF. Nat Cell Biol 19:974–987

    Article  CAS  Google Scholar 

  22. Surwit RS, Kuhn CM, Cochrane C et al (1988) Diet-induced Type II diabetes in C57BL/6J Mice. Diabetes 37:1163–1167

    Article  CAS  Google Scholar 

  23. Montgomery MK, Hallahan NL, Brown SH et al (2013) Mouse strain-dependent variation in obesity and glucose homeostasis in response to high-fat feeding. Diabetologia 56:1129–1139

    Article  CAS  Google Scholar 

  24. Zhang Y, Proenca R, Maffei M et al (1994) Positional cloning of the mouse obese gene and its human homologue. Nature 372:425–432

    Article  CAS  Google Scholar 

  25. Lutz TA, Woods SC (2012) Overview of animal models of obesity. Curr Protoc Pharmacol Chapter 5: Unit 5.61

    Google Scholar 

  26. Davie SA, Maglione JE, Manner CK et al (2007) Effects of FVB/NJ and C57Bl/6J strain backgrounds on mammary tumor phenotype in inducible nitric oxide synthase deficient mice. Transgenic Res 16:193–201

    Article  CAS  Google Scholar 

  27. Pulaski BA, Ostrand-Rosenberg S (2001) Mouse 4T1 breast tumor model. Curr Protoc Immunol. Chapter 20: Unit 20.2

    Google Scholar 

  28. Liu XZ, Pedersen L, Halberg N (2021) Cellular mechanisms linking cancers to obesity. Cell Stress 5:55–72

    Article  CAS  Google Scholar 

  29. Jove. Tail vein injection: a method to administer cancer cells for metastatic studies in a mouse model. https://www.jove.com/v/20736/tail-vein-injection-method-to-administer-cancer-cells-for-metastatic

  30. Jove. Intracardiac delivery of viral vectors: a technique to inject viral vectors intracardially to study pancreatic metastasis in murine model. https://www.jove.com/v/20317/intracardiac-delivery-viral-vectors-technique-to-inject-viral-vectors

  31. Jove. Portal vein injection: a method to study cancer metastasis to the liver. https://www.jove.com/v/20221/portal-vein-injection-a-method-to-study-cancer-metastasis-to-the-liver

  32. Power ML, Schulkin J (2008) Sex differences in fat storage, fat metabolism, and the health risks from obesity: possible evolutionary origins. Br J Nutr 99:931–940

    Article  CAS  Google Scholar 

  33. Hong J, Stubbins R, Smith R et al (2009) Differential susceptibility to obesity between male, female and ovariectomized female mice. Nutr J 8:11

    Article  Google Scholar 

  34. Casimiro I, Stull ND, Tersey SA et al (2021) Phenotypic sexual dimorphism in response to dietary fat manipulation in C57BL/6J mice. J Diabetes Complicat 35:107795

    Article  CAS  Google Scholar 

  35. Nishikawa S, Yasoshima A, Doi K et al (2007) Involvement of sex, strain and age factors in high fat diet-induced obesity in C57BL/6J and BALB/cA Mice. Exp Anim 56:263-72

    Article  Google Scholar 

  36. Shi H, Clegg DJ (2009) Sex differences in the regulation of body weight. Physiol Behav 97:199–204

    Article  CAS  Google Scholar 

  37. Pettersson US, Waldén TB, Carlsson P-O et al (2012) Female mice are protected against high-fat diet induced metabolic syndrome and increase the regulatory t cell population in adipose tissue. PLoS One 7:e46057

    Article  CAS  Google Scholar 

  38. Clements VK, Long T, Long R et al (2018) Frontline science: high fat diet and leptin promote tumor progression by inducing myeloid-derived suppressor cells. J Leukoc Biol 103:395–407

    Article  CAS  Google Scholar 

  39. Xia S, Sha H, Yang L et al (2011) Gr-1+ CD11b+ myeloid-derived suppressor cells suppress inflammation and promote insulin sensitivity in obesity. J Biol Chem 286:23591–23599

    Article  CAS  Google Scholar 

  40. Trentham-Dietz A, Newcomb PA, Egan KM et al (2000) Weight change and risk of postmenopausal breast cancer (United States). Cancer Causes Control 11:533–542

    Article  CAS  Google Scholar 

  41. García-Estévez L, Cortés J, Pérez S et al (2021) Obesity and breast cancer: a paradoxical and controversial relationship influenced by menopausal status. Front Oncol 11:705911

    Article  Google Scholar 

  42. Rogers NH, Perfield JW 2nd, Strissel KJ et al (2009) Reduced energy expenditure and increased inflammation are early events in the development of ovariectomy-induced obesity. Endocrinology 150:2161–2168

    Article  CAS  Google Scholar 

  43. Vieira Potter VJ, Strissel KJ, Xie C et al (2012) Adipose tissue inflammation and reduced insulin sensitivity in ovariectomized mice occurs in the absence of increased adiposity. Endocrinology 153:4266–4277

    Article  Google Scholar 

  44. Yakar S, Nunez NP, Pennisi P et al (2006) Increased tumor growth in mice with diet-induced obesity: impact of ovarian hormones. Endocrinology 147:5826–5834

    Article  CAS  Google Scholar 

  45. Villareal DT, Apovian CM, Kushner RF et al (2005) Obesity in older adults: technical review and position statement of the American Society for Nutrition and NAASO, The Obesity Society. Am J Clin Nutr 82:923–934

    Article  CAS  Google Scholar 

  46. Fane M, Weeraratna AT (2020) How the ageing microenvironment influences tumour progression. Nat Rev Cancer 20:89–106

    Article  CAS  Google Scholar 

  47. Haus E, Smolensky MH (1999) Biologic rhythms in the immune system. Chronobiol Int 16:581–622

    Article  CAS  Google Scholar 

  48. Haus E, Lakatua DJ, Swoyer J et al (1983) Chronobiology in hematology and immunology. Am J Anatomy 168:467–517

    Article  CAS  Google Scholar 

  49. Méndez-Ferrer S, Lucas D, Battista M et al (2008) Haematopoietic stem cell release is regulated by circadian oscillations. Nature 452:442–447

    Article  Google Scholar 

  50. Lucas D, Battista M, Shi PA et al (2008) Mobilized hematopoietic stem cell yield depends on species-specific circadian timing. Cell Stem Cell 3:364–366

    Article  CAS  Google Scholar 

  51. Dimitrov S, Benedict C, Heutling D et al (2009) Cortisol and epinephrine control opposing circadian rhythms in T cell subsets. Blood 113:5134–5143

    Article  CAS  Google Scholar 

  52. Casanova-Acebes M, Pitaval C, Weiss LA et al (2013) Rhythmic modulation of the hematopoietic niche through neutrophil clearance. Cell 153:1025–1035

    Article  CAS  Google Scholar 

  53. Wu L, Reddy AB (2013) Disrupting rhythms: diet-induced obesity impairs diurnal rhythms in metabolic tissues. Diabetes 62:1829–1830

    Article  CAS  Google Scholar 

  54. Prasai MJ, Mughal RS, Wheatcroft SB et al (2013) Diurnal variation in vascular and metabolic function in diet-induced obesity: divergence of insulin resistance and loss of clock rhythm. Diabetes 62:1981–1989

    Article  CAS  Google Scholar 

  55. Xu H, Li H, Woo SL et al (2014) Myeloid cell-specific disruption of Period1 and Period2 exacerbates diet-induced inflammation and insulin resistance. J Biol Chem 289:16374–16388

    Article  CAS  Google Scholar 

Download references

Acknowledgments

S.P. and D.Q. designed the protocols and wrote the manuscript. S.P. optimized the protocols, performed the experiments, and generated the figures.

Disclosures

The authors have no disclosures.

Author information

Authors and Affiliations

  1. Rosalind and Morris Goodman Cancer Institute, McGill University, Montreal, QC, Canada

    Sarah Petrecca & Daniela F. Quail

  2. Department of Medicine, Division of Experimental Medicine, McGill University, Montreal, QC, Canada

    Sarah Petrecca & Daniela F. Quail

  3. Department of Physiology, Faculty of Medicine, McGill University, Montreal, QC, Canada

    Daniela F. Quail

Authors
  1. Sarah Petrecca
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Daniela F. Quail
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Daniela F. Quail .

Editor information

Editors and Affiliations

  1. Lady Davis Institute for Medical Research, Jewish General Hospital, Montreal, QC, Canada

    Josie Ursini-Siegel

Rights and permissions

Reprints and permissions

Copyright information

© 2023 The Author(s), under exclusive license to Springer Science+Business Media, LLC, part of Springer Nature

About this protocol

Check for updates. Verify currency and authenticity via CrossMark

Cite this protocol

Petrecca, S., Quail, D.F. (2023). Mouse Models of Obesity to Study the Tumor-Immune Microenvironment. In: Ursini-Siegel, J. (eds) The Tumor Microenvironment. Methods in Molecular Biology, vol 2614. Humana, New York, NY. https://doi.org/10.1007/978-1-0716-2914-7_9

Download citation

  • DOI: https://doi.org/10.1007/978-1-0716-2914-7_9

  • Published:

  • Publisher Name: Humana, New York, NY

  • Print ISBN: 978-1-0716-2913-0

  • Online ISBN: 978-1-0716-2914-7

  • eBook Packages: Springer Protocols

Publish with us

Policies and ethics

Search

Navigation