Skip to main content
Log in

PPARGC1A gene polymorphism is associated with exercise-induced fat loss

  • Original Article
  • Published:
Molecular Biology Reports Aims and scope Submit manuscript

Abstract

Obesity is a widespread problem within modern society, serving to increase the risk of cardiovascular, metabolic, and neurodegenerative disorders. Peroxisome proliferator-activated receptor gamma (PPARγ) and PPARγ coactivator 1 α (PGC1α) play a key role in the regulation of cellular energy metabolism and is implicated in the pathology of these diseases. This study examined the association between polymorphisms of the PPARG and PPARGC1A genes and individual variability in weight loss in response to physical activity intervention. 39 obese Ukrainian women (44.4 ± 7.5 years, BMI > 30.0 kg/m2) undertook a 3-month fitness program whilst following a hypocaloric diet (~ 1500 cal). Anthropometric and biochemical measurements took place before and after the program. Single nucleotide polymorphisms within or near PPARG (n = 94) and PPARGC1A (n = 138) were identified and expression of PPARG mRNA was measured via reverse transcription and amplification. The association between DNA polymorphisms and exercise-induced weight loss, initial body mass, biochemistry and PPARG expression was determined using one-way analysis of variance (ANOVA). The present intervention induced significant fat loss in all participants (total fat: 40.3 ± 5.3 vs 36.4 ± 5.7%; P < 0.00001). Only one polymorphism (rs17650401 C/T) within the PPARGC1A gene was found to be associated with fat loss efficiency after correction for multiple testing, with T allele carriers showing the greatest reduction in body fat percentage (2.5-fold; P = 0.00013) compared to non-carriers. PPARGC1A (rs17650401) is associated with fat loss efficiency of the fitness program in obese women. Further studies are warranted to test whether this variation is associated with fat oxidation.

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

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Dreyer C, Krey G, Keller H, Givel F, Helftenbein G, Wahli W (1992) Control of the peroxisomal β-oxidation pathway by a novel family of nuclear hormone receptors. Cell 68:879–887. https://doi.org/10.1016/0092-8674(92)90031-7

    Article  CAS  PubMed  Google Scholar 

  2. Hong F, Xu P, Zhai Y (2018) The opportunities and challenges of peroxisome proliferator-activated receptors ligands in clinical drug discovery and development. Int J Mol Sci 19:2189. https://doi.org/10.3390/ijms19082189

    Article  CAS  PubMed Central  Google Scholar 

  3. Laganà AS, Vitale SG, Nigro A (2016) Pleiotropic actions of peroxisome proliferator-activated receptors (PPARs) in dysregulated metabolic homeostasis, inflammation and cancer: current evidence and future perspectives. Int J Mol Sci 17:999. https://doi.org/10.3390/ijms17070999

    Article  CAS  PubMed Central  Google Scholar 

  4. Korbecki J, Bobiński R, Dutka M (2019) Self-regulation of the inflammatory response by peroxisome proliferator-activated receptors. Inflamm Res 68:443–458. https://doi.org/10.1007/s00011-019-01231-1

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. Villena JA (2015) New insights into PGC-1 coactivators: redefining their role in the regulation of mitochondrial function and beyond. FEBS J 282:647–672. https://doi.org/10.1111/febs.13175

    Article  CAS  PubMed  Google Scholar 

  6. Gureev AP, Shaforostova EA, Popov VN (2019) Regulation of mitochondrial biogenesis as a way for active longevity Interaction between the Nrf2 and PGC-1α signaling pathways. Front Genet. https://doi.org/10.3389/fgene.2019.00435

  7. Diop S, Bisharat-Kernizan J, Birse R, Oldham S, Ocorr K, Bodmer R (2015) PGC-1/Spargel counteracts high-fat-diet-induced obesity and cardiac lipotoxicity downstream of TOR and brummer ATGL lipase. Cell Rep 10:1572–1584. https://doi.org/10.1016/j.celrep.2015.02.022

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  8. Monsalve FA, Pyarasani RD, Delgado-Lopez F, Moore-Carrasco R (2013) Peroxisome proliferator- activated receptor targets for the treatment of metabolic diseases. Mediators Inflamm 2013:1–18. https://doi.org/10.1155/2013/549627

    Article  CAS  Google Scholar 

  9. Bray GA, Heisel WE, Afshin A (2018) The science of obesity management: an endocrine society scientific statement. Endocr Rev 39:79–132. https://doi.org/10.1210/er.2017-00253

    Article  PubMed  PubMed Central  Google Scholar 

  10. Youssef J, Badr M (2011) Peroxisome proliferator-activated receptors and cancer: challenges and opportunities. Br J Pharmacol 164:68–82. https://doi.org/10.1111/j.1476-5381.2011.01383.x

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. Grygiel-Górniak B (2014) Peroxisome proliferator-activated receptors and their ligands: nutritional and clinical implications - a review. Nutr J 13:1–10. https://doi.org/10.1186/1475-2891-13-17

    Article  CAS  Google Scholar 

  12. Drozdovska S, Andrieieva O, Yarmak O, Blagii O (2020) Personalization of health-promoting fitness programs for young women based on genetic factors. J Phys Edu Sport 20:331–337. https://doi.org/10.7752/jpes.2020.s1046

    Article  Google Scholar 

  13. Goni L, García-Granero M, Milagro FI, Cuervo M, Martínez JA (2018) Phenotype and genotype predictors of BMI variability among European adults. Nutr Diabetes 8:1–8. https://doi.org/10.1038/s41387-018-0041-1

    Article  Google Scholar 

  14. Shamsi BH, Ma C, Naqvi S, Xiao Y (2014) Effects of pioglitazone mediated activation of PPAR-γ on CIDEC and obesity related changes in mice. PLoS ONE 9:1–8. https://doi.org/10.1371/journal.pone.0106992

    Article  CAS  Google Scholar 

  15. Puigserver P, Wu Z, Park CW, Graves R, Wright M, Spiegelman BM (1998) A cold-inducible coactivator of nuclear receptors linked to adaptive thermogenesis. Cell 92:829–839. https://doi.org/10.1016/s0092-8674(00)81410-5

    Article  CAS  PubMed  Google Scholar 

  16. Singh SP, Schragenheim J, Cao J, Falck JR, Abraham NG, Bellner L (2016) PGC-1 alpha regulates HO-1 expression, mitochondrial dynamics and biogenesis: role of epoxyeicosatrienoic acid. Prostaglandins Other Lipid Mediat 125:8–18. https://doi.org/10.1016/j.prostaglandins.2016.07.004

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. Estall JL, Kahn M, Cooper MP (2009) Sensitivity of lipid metabolism and insulin signaling to genetic alterations in hepatic peroxisome proliferator-activated receptor-γ coactivator-1α expression. Diabetes 58:1499–1508. https://doi.org/10.2337/db08-1571

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  18. Liu Y, Zhai J, Chen J, Wang X, Wen T (2019) PGC-1α protects against oxidized low-density lipoprotein and luteinizing hormone-induced granulosa cells injury through ROS-p38 pathway. Hum Cell 32:285–296. https://doi.org/10.1007/s13577-019-00252-6

    Article  CAS  PubMed  Google Scholar 

  19. St-Pierre J, Drori S, Uldry M (2006) Suppression of reactive oxygen species and neurodegeneration by the PGC-1 transcriptional coactivators. Cell 127:397–408. https://doi.org/10.1016/j.cell.2006.09.024

    Article  CAS  PubMed  Google Scholar 

  20. Sarzynski MA, Rankinen T, Sternfeld B (2013) Association of single-nucleotide polymorphisms from 17 candidate genes with baseline symptom-limited exercise test duration and decrease in duration over 20 years: the coronary artery risk development in young adults (CARDIA) fitness study. Circ Cardiovasc Genet 3:531–538. https://doi.org/10.1161/CIRCGENETICS.110.957183

    Article  Google Scholar 

  21. Vargas-ortiz K, Victoriano P, Mac MH (2019) Exercise and sirtuins : a way to mitochondrial health in skeletal muscle. J Mol Sci 20:1–11. https://doi.org/10.3390/ijms20112717

    Article  CAS  Google Scholar 

  22. Zheng W, Rogoschin J, Niehoff A (2018) Combinatory effects of phytoestrogens and exercise on body fat mass and lipid metabolism in ovariectomized female rats. J Steroid Biochem Mol Biol 178:73–81. https://doi.org/10.1016/j.jsbmb.2017.11.002

    Article  CAS  PubMed  Google Scholar 

  23. Mulya A, Haus JM, Solomon TPJ (2017) Exercise training-induced improvement in skeletal muscle PGC-1α-mediated fat metabolism is independent of dietary glycemic index. Obesity 25:721–729. https://doi.org/10.1002/oby.21799

    Article  CAS  PubMed  Google Scholar 

  24. Lee E, Hsu C, Van Den Berg D (2012) Genetic variation in peroxisome proliferator-activated receptor gamma, soy, and mammographic density in Singapore Chinese women. Cancer Epidemiol Biomarkers Prev 21:635–644. https://doi.org/10.1158/1055-9965.EPI-11-1042

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  25. Jablonski KA, McAteer JB, De Bakker PIW (2010) Common variants in 40 genes assessed for diabetes incidence and response to metformin and lifestyle intervention in the diabetes prevention program. Diabetes 59:2672–2681. https://doi.org/10.2337/db10-0543

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  26. Shen H, Tong L, Balazs R, Cotman CW (2001) Physical activity elicits sustained activation of the cyclic AMP response element-binding protein and mitogen-activated protein kinase in the rat hippocampus. Neuroscience 107(2):219–229. https://doi.org/10.1016/s0306-4522(01)00315-3

    Article  CAS  PubMed  Google Scholar 

  27. Consitt LC, Wideman L, Hickey MS, Morrison RF (2008) Phosphorylation of the JAK2–STAT5 pathway in response to acute aerobic exercise. Med Sci Sports Exerc 40(6):1031–1038. https://doi.org/10.1249/MSS.0b013e3181690760

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

Funding

There were no additional souses of funding.

Author information

Authors and Affiliations

Authors

Contributions

IIM contributed to data collection, data analysis, interpretation of results and manuscript writing; SD participated in the design of the study, data analysis, interpretation of results and manuscript writing;OA, YV, AP and IA contributed to data collection, data analysis and interpretation of results; VD participated in the design of the study, data analysis and interpretation of results; CP participated in the interpretation of results and manuscript writing; IIA participated in the design of the study, contributed to data analysis, interpretation of results and manuscript writing. All authors have read and approved the final version of the manuscript, and agree with the order of presentation of the authors.

Corresponding author

Correspondence to Iuliia Iu. Mazur.

Ethics declarations

Conflict of interest

CP is a former employee of DNAfit Life Sciences, a genetic testing company. The remaining authors declare no conflicts of interest. The funding sponsors had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript; or in the decision to publish the results.

Ethical approval

This study was approved by the National Academy of Science of Ukraine Bogomoletz Institute of Physiology Biomedical Ethics Committee, Kyiv, Ukraine (#1/18 05.04.2018). Written informed consent was obtained from the participants, and the study conformed to the guidelines and principles of the Declaration of Helsinki.

Consent to publication

All authors transfer the ownership of copyright to the journal Molecular Biology Reports should their work be published in this journal.

Additional information

Publisher's Note

Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Mazur, I.I., Drozdovska, S., Andrieieva, O. et al. PPARGC1A gene polymorphism is associated with exercise-induced fat loss. Mol Biol Rep 47, 7451–7457 (2020). https://doi.org/10.1007/s11033-020-05801-z

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11033-020-05801-z

Keywords

Navigation