Abstract
Background
Adipocytokines are signaling molecules secreted by adipose tissue contributing to the control of body fat, energy expenditure and secretion of insulin and cytokines. They have been related to the development of obesity, type-2 diabetes, cardiovascular diseases and cancer. Diet and physical activity (PA) may have beneficial effects on their level. We evaluated the effects of a 24-month dietary and/or PA intervention on plasma levels of adipocytokines as a secondary analysis in the DAMA (Diet, physical Activity and Mammography) trial.
Methods
The 234 study participants (healthy postmenopausal women with high breast density, 50–69 years, non-smokers, no hormone therapy) were randomised to four arms: (1) isocaloric dietary intervention mainly based on plant-foods; (2) moderate-intensity PA intervention with at least 1 h/week of supervised strenuous activity; (3) both interventions; (4) general recommendations on healthy dietary and PA patterns. Leptin, resistin and adiponectin were measured at baseline and at the end of the intervention. Analyses were performed using Tobit regression.
Results
After 24 months, women randomised to PA intervention (arms #2 + #3) showed significant lower level of leptin (37.5% lower) and resistin (65.6% lower) compared to the control group (arms #1 + #4). No significant differences emerged in adiponectin levels. No significant differences in leptin, resistin and adiponectin levels at follow-up emerged in women randomised to the dietary intervention (arms #1 + #3) in comparison with controls (arms #2 + #4).
Conclusion
This study supports the effectiveness of PA, even at moderate intensity, in improving the leptin and resistin profile in postmenopausal women.
Trial registration number: ISRCTN28492718, date of trial registration 17/05/2012.
Similar content being viewed by others
Data availability
The datasets generated during and/or analysed during the current study are not publicly available due to participants privacy protection but are available from the corresponding author on reasonable request.
References
Fischer-Posovszky P, Wabitsch M, Hochberg Z (2007) Endocrinology of adipose tissue—an update. Horm Metab Res 39(5):314–321. https://doi.org/10.1055/s-2007-976539
Koerner A, Kratzsch J, Kiess W (2005) Adipocytokines: leptin–the classical, resistin–the controversial, adiponectin–the promising, and more to come. Best Pract Res Clin Endocrinol Metab 19(4):525–546. https://doi.org/10.1016/j.beem.2005.07.008
Ollberding NJ, Kim Y, Shvetsov YB, Wilkens LR, Franke AA, Cooney RV, Maskarinec G, Hernandez BY, Henderson BE, Le Marchand L, Kolonel LN, Goodman MT (2013) Prediagnostic leptin, adiponectin, C-reactive protein, and the risk of postmenopausal breast cancer. Cancer Prev Res (Phila) 6(3):188–195. https://doi.org/10.1158/1940-6207.CAPR-12-0374
van Gemert WA, May AM, Schuit AJ, Oosterhof BY, Peeters PH, Monninkhof EM (2016) Effect of weight loss with or without exercise on inflammatory markers and adipokines in postmenopausal women: the SHAPE-2 trial, a randomized controlled trial. Cancer Epidemiol Biomarkers Prev 25(5):799–806. https://doi.org/10.1158/1055-9965.epi-15-1065
Badoer E (2021) Cardiovascular and metabolic crosstalk in the brain: leptin and resistin. Front Physiol 12:639417. https://doi.org/10.3389/fphys.2021.639417
Ward LJ, Nilsson S, Hammar M, Lindh-Åstrand L, Berin E, Lindblom H, Spetz Holm AC, Rubér M, Li W (2020) Resistance training decreases plasma levels of adipokines in postmenopausal women. Sci Rep 10(1):19837. https://doi.org/10.1038/s41598-020-76901-w
Lizcano F, Guzmán G (2014) Estrogen Deficiency and the origin of obesity during menopause. Biomed Res Int 2014:757461. https://doi.org/10.1155/2014/757461
Malutan AM, Dan M, Nicolae C, Carmen M (2014) Proinflammatory and anti-inflammatory cytokine changes related to menopause. Prz Menopauzalny 13(3):162–168. https://doi.org/10.5114/pm.2014.43818
Weitzmann MN, Pacifici R (2006) Estrogen deficiency and bone loss: an inflammatory tale. J Clin Invest 116(5):1186–1194. https://doi.org/10.1172/jci28550
King B, Jiang Y, Su X, Xu J, Xie L, Standard J, Wang W (2013) Weight control, endocrine hormones and cancer prevention. Exp Biol Med (Maywood) 238(5):502–508. https://doi.org/10.1177/1535370213480695
Masala G, Assedi M, Caini S, Ermini I, Occhini D, Castaldo M, Bendinelli B, Zagni D, Tanzini D, Saieva C, Ambrogetti D, Palli D (2014) The DAMA trial: a diet and physical activity intervention trial to reduce mammographic breast density in postmenopausal women in Tuscany, Italy. Study protocol and baseline characteristics. Tumori 100(4):377–385. https://doi.org/10.1700/1636.17890
Masala G, Assedi M, Sera F, Ermini I, Occhini D, Castaldo M, Pierpaoli E, Caini S, Bendinelli B, Ambrogetti D, Palli D (2019) Can dietary and physical activity modifications reduce breast density in postmenopausal women? The DAMA study, a randomized intervention trial in Italy. Cancer Epidemiol Biomarkers Prev 28(1):41–50. https://doi.org/10.1158/1055-9965.epi-18-0468
American College of Radiology (2003) The ACR Breast Imaging Reporting and Data System (BI-RADS®). American College of Radiology, Reston
Palli D, Berrino F, Vineis P, Tumino R, Panico S, Masala G, Saieva C, Salvini S, Ceroti M, Pala V, Sieri S, Frasca G, Giurdanella MC, Sacerdote C, Fiorini L, Celentano E, Galasso R, Decarli A, Krogh V (2003) EPIC-Italy: a molecular epidemiology project on diet and cancer: the EPIC-Italy Prospective Study. Design and baseline characteristics of participants. Tumori 89:586–593. https://doi.org/10.1177/030089160308900602
Masala G, Bendinelli B, Della Bella C, Assedi M, Tapinassi S, Ermini I, Occhini D, Castaldo M, Saieva C, Caini S, D’Elios MM, Palli D (2020) Inflammatory marker changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women. Sci Rep 10(1):21845. https://doi.org/10.1038/s41598-020-78796-z
Hewett P, Ganser GH (2007) A comparison of several methods for analyzing censored data. Ann Occup Hyg 51(7):611–632. https://doi.org/10.1093/annhyg/mem045
Hornung RW, Reed LD (1990) Estimation of average concentration in the presence of non detectable values. Appl Occup Environ Hyg 5:46–51. https://doi.org/10.1080/1047322X.1990.10389587
Lubin JH, Colt JS, Camann D, Davis S, Cerhan JR, Severson RK, Bernstein L, Hartge P (2004) Epidemiologic evaluation of measurement data in the presence of detection limits. Environ Health Perspect 112(17):1691–1696. https://doi.org/10.1289/ehp.7199
Ballenberger N, Lluis A, von Mutius E, Illi S, Schaub B (2012) Novel statistical approaches for non-normal censored immunological data: analysis of cytokine and gene expression data. PLoS ONE 7(10):e46423. https://doi.org/10.1371/journal.pone.0046423
McAlister FA, Straus SE, Sackett DL, Altman DG (2003) Analysis and reporting of factorial trials: a systematic review. JAMA 289(19):2545–2553. https://doi.org/10.1001/jama.289.19.2545
Marcelino-Rodríguez I, Almeida Gonzalez D, Alemán-Sánchez JJ, Brito Díaz B, Rodríguez Pérez MDC, Gannar F, Domínguez Coello S, Cuevas Fernández FJ, Cabrera de León A (2017) Inverse association of resistin with physical activity in the general population. PLoS ONE 12(8):e0182493. https://doi.org/10.1371/journal.pone.0182493
Rava A, Pihlak A, Kums T, Purge P, Pääsuke M, Jürimäe J (2020) Resistin concentration is inversely associated with objectively measured physical activity in healthy older women. Aging Clin Exp Res 32(3):475–481. https://doi.org/10.1007/s40520-019-01222-6
Gondim OS, de Camargo VT, Gutierrez FA, Martins PF, Passos ME, Momesso CM, Santos VC, Gorjão R, Pithon-Curi TC, Cury-Boaventura MF (2015) Benefits of regular exercise on inflammatory and cardiovascular risk markers in normal weight, overweight and obese adults. PLoS ONE 10(10):e0140596. https://doi.org/10.1371/journal.pone.0140596
Neilson HK, Conroy SM, Friedenreich CM (2013) The influence of energetic factors on biomarkers of postmenopausal breast cancer risk. Curr Nutr Rep 3(1):22–34. https://doi.org/10.1007/s13668-013-0069-8
Hong HR, Jeong JO, Kong JY, Lee SH, Yang SH, Ha CD, Kang HS (2014) Effect of walking exercise on abdominal fat, insulin resistance and serum cytokines in obese women. J Exerc Nutrition Biochem 18(3):277–285. https://doi.org/10.5717/jenb.2014.18.3.277
Kim DY, Seo BD, Kim D (2014) Effect of walking exercise on changes in cardiorespiratory fitness, metabolic syndrome markers, and high-molecular-weight adiponectin in obese middle-aged women. J Phys Ther Sci 26(11):1723–1727. https://doi.org/10.1589/jpts.26.1723
Lakhdar N, Denguezli M, Zaouali M, Zbidi A, Tabka Z, Bouassida A (2014) Six months training alone or combined with diet alters HOMA-AD, HOMA-IR and plasma and adipose tissue adiponectin in obese women. Neuro Endocrinol Lett 35(5):373–379
Polito R, Monda V, Nigro E, Messina A, Di Maio G, Giuliano MT, Orrù S, Imperlini E, Calcagno G, Mosca L, Mollica MP, Trinchese G, Scarinci A, Sessa F, Salerno M, Marsala G, Buono P, Mancini A, Monda M, Daniele A, Messina G (2020) The important role of adiponectin and Orexin-A, two key proteins improving healthy status: focus on physical activity. Front Physiol 11:356. https://doi.org/10.3389/fphys.2020.00356
Eichelmann F, Schwingshackl L, Fedirko V, Aleksandrova K (2016) Effect of plant-based diets on obesity-related inflammatory profiles: a systematic review and meta-analysis of intervention trials. Obes Rev 17(11):1067–1079. https://doi.org/10.1111/obr.12439
Sofi F, Dinu M, Pagliai G, Cesari F, Gori AM, Sereni A, Becatti M, Fiorillo C, Marcucci R, Casini A (2018) Low-calorie vegetarian versus Mediterranean diets for reducing body weight and improving cardiovascular risk profile: CARDIVEG study (Cardiovascular Prevention With Vegetarian Diet). Circulation 137(11):1103–1113. https://doi.org/10.1161/circulationaha.117.030088
Dinu M, Colombini B, Pagliai G, Cesari F, Gori A, Giusti B, Marcucci R, Sofi F (2020) Effects of a dietary intervention with Mediterranean and vegetarian diets on hormones that influence energy balance: results from the CARDIVEG study. Int J Food Sci Nutr 71(3):362–369. https://doi.org/10.1080/09637486.2019.1658723
Acknowledgements
The authors wish to thank all the participants of the DAMA Trial and the staff personnel involved in the different phases of the study. Members and volunteers of a local consumers cooperative (UNICOOP-Firenze) are also acknowledged for their support to the study cooking activities.
Funding
This work was supported by Istituto Toscano Tumori–ITT (Grant 2009–2012 to GM); Ministry of Health (Programma Integrato Oncologia 2006 coordinated by DP); Associazione Italiana per la Ricerca contro il Cancro (AIRC) Milan, Italy (IG 2015 Grant Number 17146 to DP).
Author information
Authors and Affiliations
Contributions
GM and DP conceived and designed the study. DO, MC, IE, BB, CS and SC contributed to the trial activity, data acquisition and sample retrieval. MMD’E, CDB, MB and SP performed the laboratory analyses. GM, MA and BB managed and analysed the data. GM, BB, MMD’E and DP wrote, revised and approved the manuscript. All the authors contributed to the results interpretation and read and approved the submitted version of the manuscript.
Corresponding author
Ethics declarations
Conflict of interest
The authors declare that they have no conflict of interest.
Ethical standards
The DAMA trial was approved by the Ethics Committee of the Local Health Authority “Azienda Sanitaria Firenze” (ethical approval number: 15/2007/CEL). The DAMA trial was performed in accordance with the ethical standards laid down in the 1964 Declaration of Helsinki and its later amendments. Informed consent was obtained from all participants.
Rights and permissions
Springer Nature or its licensor (e.g. a society or other partner) holds exclusive rights to this article under a publishing agreement with the author(s) or other rightsholder(s); author self-archiving of the accepted manuscript version of this article is solely governed by the terms of such publishing agreement and applicable law.
About this article
Cite this article
Bendinelli, B., Masala, G., Bella, C.D. et al. Adipocytokine plasma level changes in a 24-month dietary and physical activity randomised intervention trial in postmenopausal women. Eur J Nutr 62, 1185–1194 (2023). https://doi.org/10.1007/s00394-022-03055-y
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00394-022-03055-y