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.

  • Original Article
  • Published:

Animal Models

The effects of weight cycling on lifespan in male C57BL/6J mice

International Journal of Obesity volume 37, pages 1088–1094 (2013)Cite this article

Subjects

Abstract

Objective:

With the increasing rates of obesity, many people diet in an attempt to lose weight. As weight loss is seldom maintained in a single effort, weight cycling is a common occurrence. Unfortunately, reports from clinical studies that have attempted to determine the effect of weight cycling on mortality are in disagreement, and to date, no controlled animal study has been performed to assess the impact of weight cycling on longevity. Therefore, our objective was to determine whether weight cycling altered lifespan in mice that experienced repeated weight gain and weight loss throughout their lives.

Methods:

Male C57BL/6J mice were placed on one of three lifelong diets: a low-fat (LF) diet, a high-fat (HF) diet or a cycled diet in which the mice alternated between 4 weeks on the LF diet and 4 weeks on the HF diet. Body weight, body composition, several blood parameters and lifespan were assessed.

Results:

Cycling between the HF and LF diet resulted in large fluctuations in body weight and fat mass. These gains and losses corresponded to significant increases and decreases, respectively, in leptin, resistin, GIP, IGF-1, glucose, insulin and glucose tolerance. Surprisingly, weight cycled mice had no significant difference in lifespan (801±45 days) as compared to LF-fed controls (828±74 days), despite being overweight and eating a HF diet for half of their lives. In contrast, the HF-fed group experienced a significant decrease in lifespan (544±73 days) compared with LF-fed controls and cycled mice.

Conclusions:

This is the first controlled mouse study to demonstrate the effect of lifelong weight cycling on longevity. The act of repeatedly gaining and losing weight, in itself, did not decrease lifespan and was more beneficial than remaining obese.

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
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  1. National Task Force on the Prevention and Treatment of Obesity. Weight cycling. JAMA 1994; 272: 1196–1202.

    Article  Google Scholar 

  2. French SA, Jeffery RW, Folsom AR, Williamson DF, Byers T . Weight variability in a population-based sample of older women: reliability and intercorrelation of measures. Int J Obes Relat Metab Disord 1995; 19: 22–29.

    CAS  PubMed  Google Scholar 

  3. Field AE, Malspeis S, Willett WC . Weight cycling and mortality among middle-aged or older women. Arch Intern Med 2009; 169: 881–886.

    Article  Google Scholar 

  4. Stevens VL, Jacobs EJ, Sun J, Patel AV, McCullough ML, Teras LR et al. Weight Cycling and Mortality in a Large Prospective US Study. Am J Epidemiol 2012; 175: 785–792.

    Article  Google Scholar 

  5. Stevens VL, Jacobs EJ, Sun J, McCullough ML, Patel AV, Gaudet MM et al. Weight cycling and risk of endometrial cancer. Cancer Epidemio Biomarkers Prev 2012; 21: 747–752.

    Article  Google Scholar 

  6. Kraschnewski JL, Boan J, Esposito J, Sherwood NE, Lehman EB, Kephart DK et al. Long-term weight loss maintenance in the United States. Int J Obes 2010; 34: 1644–1654.

    Article  CAS  Google Scholar 

  7. Yang D, Fontaine KR, Wang C, Allison DB . Weight loss causes increased mortality: cons. Obes Rev 2003; 4: 9–16.

    Article  CAS  Google Scholar 

  8. Diaz VA, Mainous AG, Everett CJ . The association between weight fluctuation and mortality: results from a population-based cohort study. J Community Health 2005; 30: 153–165.

    Article  Google Scholar 

  9. Rzehak P, Meisinger C, Woelke G, Brasche S, Strube G, Heinrich J . Weight change, weight cycling and mortality in the ERFORT Male Cohort Study. Eur J Epidemiol 2007; 22: 665–673.

    Article  Google Scholar 

  10. Pi-Sunyer X, Blackburn G, Brancati FL, Bray GA, Bright R, Clark JM et al. Reduction in weight and cardiovascular disease risk factors in individuals with type 2 diabetes: one-year results of the look AHEAD trial. Diabetes Care 2007; 30: 1374–1383.

    Article  Google Scholar 

  11. Villareal DT, Miller BV, Banks M, Fontana L, Sinacore DR, Klein S . Effect of lifestyle intervention on metabolic coronary heart disease risk factors in obese older adults. Am J Clin Nutr 2006; 84: 1317–1323.

    Article  CAS  Google Scholar 

  12. Lissner L, Andres R, Muller DC, Shimokata H . Body weight variability in men: metabolic rate, health and longevity. Int J Obes 1990; 14: 373–383.

    CAS  PubMed  Google Scholar 

  13. Dyer AR, Stamler J, Greenland P . Associations of weight change and weight variability with cardiovascular and all-cause mortality in the Chicago Western Electric Company Study. Am J Epidemiol 2000; 152: 324–333.

    Article  CAS  Google Scholar 

  14. Wannamethee SG, Shaper AG, Walker M . Weight change, weight fluctuation, and mortality. Arch Intern Med 2002; 162: 2575–2580.

    Article  Google Scholar 

  15. Gregg EW, Gerzoff RB, Thompson TJ, Williamson DF . Intentional weight loss and death in overweight and obese U.S. adults 35 years of age and older. Ann Intern Med 2003; 138: 383–389.

    Article  Google Scholar 

  16. Shea MK, Houston DK, Nicklas BJ, Messier SP, Davis CC, Miller ME et al. The effect of randomization to weight loss on total mortality in older overweight and obese adults: the ADAPT Study. J Gerontol A Biol Sci Med Sci 2010; 65: 519–525.

    Article  Google Scholar 

  17. Lissner L, Odell PM, D'Agostino RB, Stokes J, Kreger BE, Belanger AJ et al. Variability of body weight and health outcomes in the Framingham population. N Engl J Med 1991; 324: 1839–1844.

    Article  CAS  Google Scholar 

  18. Blair SN, Shaten J, Brownell K, Collins G, Lissner L . Body weight change, all-cause mortality, and cause-specific mortality in the Multiple Risk Factor Intervention Trial. Ann Intern Med 1993; 119 (7 Pt 2): 749–757.

    Article  CAS  Google Scholar 

  19. Folsom AR, French SA, Zheng W, Baxter JE, Jeffery RW . Weight variability and mortality: the Iowa Women's Health Study. Int J Obes Relat Metab Disord 1996; 20: 704–709.

    CAS  PubMed  Google Scholar 

  20. Mikkelsen KL, Heitmann BL, Keiding N, Sorensen TI . Independent effects of stable and changing body weight on total mortality. Epidemiology 1999; 10: 671–678.

    Article  CAS  Google Scholar 

  21. Simpson JA, Wainwright PE, Hoffman-Goetz L, Levesque S . Effects of different weight loss treatments on weight cycling and metabolic measures in male mice. Physiol Behav 1994; 56: 197–201.

    Article  CAS  Google Scholar 

  22. Jen KL, Lu H, Savona L, Watkins A, Shaw M . Long-term weight cycling reduces body weight and fat free mass, but not fat mass in female Wistar rats. Int J Obes Relat Metab Disord 1995; 19: 699–708.

    CAS  PubMed  Google Scholar 

  23. Lauer JB, Reed GW, Hill JO . Effects of weight cycling induced by diet cycling in rats differing in susceptibility to dietary obesity. Obes Res 1999; 7: 215–222.

    Article  CAS  Google Scholar 

  24. Pellizzon MA, Buison AM, Jen KL . Short-term weight cycling in aging female rats increases rate of weight gain but not body fat content. Int J Obes Relat Metab Disord 2000; 24: 236–245.

    Article  CAS  Google Scholar 

  25. Li X, Cope MB, Johnson MS, Smith DL, Nagy TR . Mild calorie restriction induces fat accumulation in female C57BL/6J mice. Obesity 2010; 18: 456–462.

    Article  Google Scholar 

  26. Surwit RS, Kuhn CM, Cochrane C, McCubbin JA, Feinglos MN . Diet-induced type II diabetes in C57BL/6J mice. Diabetes 1988; 37: 1163–1167.

    Article  CAS  Google Scholar 

  27. List EO, Berryman DE, Palmer AJ, Qiu L, Sankaran S, Kohn DT et al. Analysis of mouse skin reveals proteins that are altered in a diet-induced diabetic state: a new method for detection of type 2 diabetes. Proteomics 2007; 7: 1140–1149.

    Article  CAS  Google Scholar 

  28. List EO, Palmer AJ, Berryman DE, Bower B, Kelder B, Kopchick JJ . Growth hormone improves body composition, fasting blood glucose, glucose tolerance and liver triacylglycerol in a mouse model of diet-induced obesity and type 2 diabetes. Diabetologia 2009; 52: 1647–1655.

    Article  CAS  Google Scholar 

  29. Berryman DE, List EO, Palmer AJ, Chung MY, Wright-Piekarski J, Lubbers E et al. Two-year body composition analyses of long-lived GHR null mice. J Gerontol A Biol Sci Med Sci 2010; 65: 31–40.

    Article  Google Scholar 

  30. Palmer AJ, Chung MY, List EO, Walker J, Okada S, Kopchick JJ et al. Age-related changes in body composition of bovine growth hormone transgenic mice. Endocrinology 2009; 150: 1353–1360.

    Article  CAS  Google Scholar 

  31. Silberberg M, Silberberg R . Factors modifying the lifespan of mice. Am J Physiol 1954; 177: 23–26.

    Article  CAS  Google Scholar 

  32. Keipert S, Voigt A, Klaus S . Dietary effects on body composition, glucose metabolism, and longevity are modulated by skeletal muscle mitochondrial uncoupling in mice. Aging Cell 2011; 10: 122–136.

    Article  CAS  Google Scholar 

  33. Berryman DE, Christiansen JS, Johannsson G, Thorner MO, Kopchick JJ . Role of the GH/IGF-1 axis in lifespan and healthspan: lessons from animal models. Growth Horm IGF Res 2008; 18: 455–471.

    Article  CAS  Google Scholar 

  34. Bonafe M, Barbieri M, Marchegiani F, Olivieri F, Ragno E, Giampieri C et al. Polymorphic variants of insulin-like growth factor I (IGF-I) receptor and phosphoinositide 3-kinase genes affect IGF-I plasma levels and human longevity: cues for an evolutionarily conserved mechanism of life span control. J Clin Endocrinol Metab 2003; 88: 3299–3304.

    Article  CAS  Google Scholar 

  35. van Heemst D, Beekman M, Mooijaart SP, Heijmans BT, Brandt BW, Zwaan BJ et al. Reduced insulin/IGF-1 signalling and human longevity. Aging Cell 2005; 4: 79–85.

    Article  CAS  Google Scholar 

  36. Euser SM, van Heemst D, van Vliet P, Breteler MM, Westendorp RG . Insulin/Insulin-like growth factor-1 signaling and cognitive function in humans. J Gerontol A Biol Sci Med Sci 2008; 63: 907–910.

    Article  Google Scholar 

  37. List EO, Sackmann-Sala L, Berryman DE, Funk K, Kelder B, Gosney ES et al. Endocrine parameters and phenotypes of the growth hormone receptor gene disrupted (GHR−/−) mouse. Endocr Rev 2011; 32: 356–386.

    Article  CAS  Google Scholar 

  38. van Heemst D . Insulin, IGF-1 and longevity. Aging Dis 2010; 1: 147–157.

    PubMed  PubMed Central  Google Scholar 

  39. Suh Y, Atzmon G, Cho MO, Hwang D, Liu B, Leahy DJ et al. Functionally significant insulin-like growth factor I receptor mutations in centenarians. Proc Natl Acad Sci USA 2008; 105: 3438–3442.

    Article  CAS  Google Scholar 

  40. LeRoith D, Roberts CT . The insulin-like growth factor system and cancer. Cancer Lett 2003; 195: 127–137.

    Article  CAS  Google Scholar 

  41. Doyle SL, Donohoe CL, Finn SP, Howard JM, Lithander FE, Reynolds JV et al. IGF-1 and its receptor in esophageal cancer: association with adenocarcinoma and visceral obesity. Am J Gastroenterol 2012; 107: 196–204.

    Article  CAS  Google Scholar 

  42. Giovannini S, Onder G, Liperoti R, Russo A, Carter C, Capoluongo E et al. Interleukin-6, C-reactive protein, and tumor necrosis factor-alpha as predictors of mortality in frail, community-living elderly individuals. J Am Geriatr Soc 2011; 59: 1679–1685.

    Article  Google Scholar 

  43. Walston JD, Matteini AM, Nievergelt C, Lange LA, Fallin DM, Barzilai N et al. Inflammation and stress-related candidate genes, plasma interleukin-6 levels, and longevity in older adults. Exp Gerontol 2009; 44: 350–355.

    Article  CAS  Google Scholar 

  44. Caruso C, Lio D, Cavallone L, Franceschi C . Aging, longevity, inflammation, and cancer. Ann N Y Acad Sci 2004; 1028: 1–13.

    Article  CAS  Google Scholar 

  45. Wassel CL, Barrett-Connor E, Laughlin GA . Association of circulating C-reactive protein and interleukin-6 with longevity into the 80 s and 90 s: The Rancho Bernardo Study. J Clin Endocrinol Metab 2010; 95: 4748–4755.

    Article  CAS  Google Scholar 

  46. Arranz L, Lord JM, De la Fuente M . Preserved ex vivo inflammatory status and cytokine responses in naturally long-lived mice. Age 2010; 32: 451–466.

    Article  CAS  Google Scholar 

  47. Rattan SI . Hormesis in aging. Ageing Res Rev 2008; 7: 63–78.

    Article  Google Scholar 

  48. Rodin J, Radke-Sharpe N, Rebuffe-Scrive M, Greenwood MR . Weight cycling and fat distribution. Int J Obes 1990; 14: 303–310.

    CAS  Google Scholar 

  49. Wallner SJ, Luschnigg N, Schnedl WJ, Lahousen T, Sudi K, Crailsheim K et al. Body fat distribution of overweight females with a history of weight cycling. Int J Obes Relat Metab Disord 2004; 28: 1143–1148.

    Article  CAS  Google Scholar 

  50. Tran TT, Yamamoto Y, Gesta S, Kahn CR . Beneficial effects of subcutaneous fat transplantation on metabolism. Cell Metab 2008; 7: 410–420.

    Article  CAS  Google Scholar 

Download references

Acknowledgements

This work was supported in part by the State of Ohio’s Eminent Scholar Program that includes a gift from Milton and Lawrence Goll, by NIH grants AG031736 and DK083729, by the AMVETS, by the Gates Millennium Scholarship program and by the Diabetes Institute at Ohio University.

Author information

Authors and Affiliations

  1. Edison Biotechnology Institute, Konneker Research Laboratories, Ohio University, Athens, OH, USA

    E O List, D E Berryman, J Wright-Piekarski, A Jara, K Funk & J J Kopchick

  2. Department of Specialty Medicine, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA

    E O List

  3. School of Applied Health Sciences and Wellness, College of Health Sciences and Professions, Ohio University, Athens, OH, USA

    D E Berryman

  4. Department of Biomedical Sciences, Heritage College of Osteopathic Medicine, Ohio University, Athens, OH, USA

    D E Berryman, A Jara & J J Kopchick

Authors
  1. E O List
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. D E Berryman
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. J Wright-Piekarski
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. A Jara
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. K Funk
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. J J Kopchick
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to E O List.

Ethics declarations

Competing interests

The authors declare no conflict of interest.

Rights and permissions

Reprints and permissions

About this article

Cite this article

List, E., Berryman, D., Wright-Piekarski, J. et al. The effects of weight cycling on lifespan in male C57BL/6J mice. Int J Obes 37, 1088–1094 (2013). https://doi.org/10.1038/ijo.2012.203

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/ijo.2012.203

Keywords

This article is cited by

Search

Advanced search

Quick links