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.

  • Paper
  • Published:

Obesity, macrophage migration inhibitory factor, and weight loss

Abstract

OBJECTIVE:

Elevated macrophage migration inhibitory factor (MIF) has been implicated as a causal mechanism in a number of disease conditions including cardiovascular disease (CVD), diabetes, and cancer. Excess body fat is associated with an increased risk of numerous health conditions including CVD, diabetes, and cancer. To our knowledge, the association between MIF and obesity status and the effect of weight loss on serum MIF concentrations have not been reported. In this study, we examined the effects of participation in a behavior-based weight loss program on MIF concentrations in obese individuals.

SUBJECTS:

Study participants were 71 men and women enrolled in The Cooper Institute Weight Management Program. Participants were predominantly female (68%, n=48), middle-aged (46.5±9.8 y), and severely obese (BMI=43.0±8.6).

METHOD:

Plasma MIF concentrations and other standard risk factors were measured before and after participation in a diet and physical activity based weight management program.

RESULTS:

The mean follow-up was 8.5±3.0 months with an average weight loss of 14.4 kg (P<0.001). The majority of clinical risk factors significantly improved at follow-up. Median levels of plasma MIF concentration were significantly lower at follow-up (median [IQR]; 5.1[3.6–10.3]) compared to baseline (8.4 [4.3–48.8]; P=0.0005). The percentage of participants with plasma MIF concentration ≥19.5 mg/nl (highest tertile at baseline) decreased from 33.8 to 5.6% (P<0.001). Further, elevated baseline plasma MIF concentration was associated with markers of β-cell dysfunction and reductions in MIF were associated with improvements in β-cell function.

CONCLUSIONS:

Circulating MIF concentrations are elevated in obese but otherwise healthy individuals; however, this elevation in MIF is not uniform across individuals. In obese individuals with elevated circulating MIF concentrations, participation in physical activity and a dietary-focused weight management program resulted in substantial reduction in MIF.

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

Access options

Buy this article

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

Figure 1
Figure 2
Figure 3

Similar content being viewed by others

References

  1. Fingerle-Rowson GR, Bucala R . Neuroendocrine properties of macrophage migration inhibitory factor (MIF). Immunol Cell Biol 2001; 79/4: 368–375.

    Article  Google Scholar 

  2. Donn RP, Ray DW . Macrophage migration inhibitory factor: molecular, cellular and genetic aspects of a key neuroendocrine molecule. J Endocrinol 2004; 182/1: 1–9.

    Article  Google Scholar 

  3. Pan JH, Sukhova GK, Yang JT, Wang B, Xie T, Fu H, Zhang Y, Satoskar AR, David JR, Metz CN, Bucala R, Fang K, Simon DI, Chapman HA, Libby P, Shi GP . Macrophage migration inhibitory factor deficiency impairs atherosclerosis in low-density lipoprotein receptor-deficient mice. Circulation 2004; 109/25: 3149–3153.

    Article  Google Scholar 

  4. Chen Z, Sakuma M, Zago AC, Zhang X, Shi C, Leng L, Mizue Y, Bucala R, Simon D . Evidence for a role of macrophage migration inhibitory factor in vascular disease. Arterioscler Thromb Vasc Biol 2004; 24/4: 709–714.

    Article  Google Scholar 

  5. Schober A, Bernhagen J, Thiele M, Zeiffer U, Knarren S, Roller M, Bucala R, Weber C . Stabilization of atherosclerotic plaques by blockade of macrophage migration inhibitory factor after vascular injury in apolipoprotein E-deficient mice. Circulation 2004; 109/3: 380–385.

    Article  Google Scholar 

  6. Waeber G, Calandra T, Roduit R, Haefliger JA, Bonny C, Thompson N, Thorens B, Temler E, Meinhardt A, Bacher M, Metz CN, Nicod P, Bucala R . Insulin secretion is regulated by the glucose-dependent production of islet beta cell macrophage migration inhibitory factor. Proc Natl Acad Sci USA 1997; 94/9: 4782–4787.

    Article  Google Scholar 

  7. Plaisance V, Thompson N, Niederhauser G, Haefliger JA, Nicod P, Waeber G, Abderrahmani A . The mif gene is transcriptionally regulated by glucose in insulin-secreting cells. Biochem Biophys Res Commun 2002; 295/1: 174–181.

    Article  Google Scholar 

  8. Mitchell RA . Mechanisms and effectors of MIF-dependent promotion of tumourigenesis. Cell Signal 2004; 16/1: 13–19.

    Article  Google Scholar 

  9. Lue H, Kleemann R, Calandra T, Roger T, Bernhagen J . Macrophage migration inhibitory factor (MIF): mechanisms of action and role in disease. Microbes Infect 2002; 4/4: 449–460.

    Article  Google Scholar 

  10. Sakaue S, Nishihira J, Hirokawa J, Yoshimura H, Honda T, Aoki K, Tagami S, Kawakami Y . Regulation of macrophage migration inhibitory factor (MIF) expression by glucose and insulin in adipocytes in vitro. Mol Med 1999; 5/6: 361–371.

    Article  Google Scholar 

  11. National Institutes of Health and National Heart, Lung, and Blood Institute. Clinical guidelines on the identification, evaluation, and treatment of overweight and obesity in adults: The evidence report. National Institutes of Health and National Heart, Lung, and Blood Institute Rockville: MD; pp 1–228; 1998.

  12. Marlatt GA, Gordon JR . Determinants of relapse: implications for the maintenance of behavior change. In: Davidson PO (ed). Behavioral medicine: changing health lifestyles. Pergamon: Elmsford, NY; 1980. pp 410–452.

    Google Scholar 

  13. Isidori AM, Kaltsas GA, Korbonits M, Pyle M, Gueorguiev M, Meinhardt A, Metz C, Petrovsky N, Popovic V, Bucala R, Grossman AB . Response of serum macrophage migration inhibitory factor levels to stimulation or suppression of the hypothalamo-pituitary-adrenal axis in normal subjects and patients with Cushing's disease. J Clin Endocrinol Metab 2002; 87/4: 1834–1840.

    Google Scholar 

  14. Petrovsky N, Socha L, Silva D, Grossman AB, Metz C, Bucala R . Macrophage migration inhibitory factor exhibits a pronounced circadian rhythm relevant to its role as a glucocorticoid counter-regulator. Immunol Cell Biol 2003; 81/2: 137–143.

    Article  Google Scholar 

  15. Yabunaka N, Nishihira J, Mizue Y, Tsuji M, Kumagai M, Ohtsuka Y, Imamura M, Asaka M . Elevated serum content of macrophage migration inhibitory factor in patients with type 2 diabetes. Diabetes Care 2000; 23/2: 256–258.

    Article  Google Scholar 

  16. Vozarova B, Stefan N, Hanson R, Lindsay RS, Bogardus C, Tataranni PA, Metz C, Bucala R . Plasma concentrations of macrophage migration inhibitory factor are elevated in Pima Indians compared to Caucasians and are associated with insulin resistance. Diabetologia 2002; 45/12: 1739–1741.

    Google Scholar 

  17. Benigni F, Atsumi T, Calandra T, Metz C, Echtenacher B, Peng T, Bucala R . The proinflammatory mediator macrophage migration inhibitory factor induces glucose catabolism in muscle. J Clin Invest 2000; 106/10: 1291–1300.

    Article  Google Scholar 

Download references

Acknowledgements

We thank our many participants, Abby Hyman for her help with the clinical examinations and data acquisition, Pat McDonald and her staff of the Cooper Clinic, the Management Information Systems division at The Cooper Institute for data entry and management, and Melba Morrow for editorial assistance.

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to T S Church.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Church, T., Willis, M., Priest, E. et al. Obesity, macrophage migration inhibitory factor, and weight loss. Int J Obes 29, 675–681 (2005). https://doi.org/10.1038/sj.ijo.0802942

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ijo.0802942

Keywords

This article is cited by

Search

Quick links