Skip to main content

Advertisement

SpringerLink
Log in

Do Health Promoting Compounds of Flaxseed Attenuate Weight Gain Via Modulation of Obesity Gene Expression?

  • Original Paper
  • Published:
Plant Foods for Human Nutrition Aims and scope Submit manuscript

Abstract

Diet-induced obesity (DIO) has been shown to increase DNA methyltransferases (DNMTs) expression and DNMTs binding at obesity-associated genes. Natural compounds have the potential to reverse obesity-associated gene expression via the regulation of DNA methylation. The objective of this study was to determine the effect of health promoting compounds of flaxseed on DNMTs and obesity-associated gene expression and weight gain. Sixty C57BL/6J male mice were randomly assigned into one of the following diet groups and fed for eight weeks: 45% kcal fat; 45% kcal fat+10% whole flaxseed; 45% kcal fat+6% defatted flaxseed; 45% kcal fat+4% flaxseed oil; and 16% kcal fat. DNMT1, DNMT3a, DNMT3b, leptin, and peroxisome proliferator-activated receptor (PPAR)-α expressions in adipose and muscle tissues were determined by real-time PCR. The health promoting compounds of flaxseed affected selected gene expression and attenuated weight gain. Further research is needed to identify the specific mechanisms modulating leptin or PPAR-α expression during DIO development.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Centers for Disease Control and Prevention. Overweight and obesity (2018) https://www.cdc.gov/obesity/data/adult.html. Accessed 15 January 2020

  2. Baranova A, Collantes R, Gowder SJ, Elariny H, Schlauch K, Younoszai A, King S, Randhawa M, Pusulury S, Alsheddi T, Ong JP, Martin LM, Chandhoke V, Younossi ZM (2005) Obesity-related differential gene expression in the visceral adipose tissue. Obes Surg 15:758–765

    Article  Google Scholar 

  3. Anunciado-Koza RP, Manuel J, Koza RA (2016) Molecular correlates of fat mass expansion in C57BL/6J mice after short-term exposure to dietary fat. Ann NY Acad Sci 1:50–58

    Article  Google Scholar 

  4. Moraes RC, Blondet A, Birkenkamp-Demtroeder K, Tirard J, Orntoft TF, Gertler A, Durand P, Naville D, Bégeot M (2003) Study of the alteration of gene expression in adipose tissue of diet-induced obese mice by microarray and reverse transcription-polymerase chain reaction analyses. Endocrinology 144:4773–4782

    Article  CAS  Google Scholar 

  5. Miller RS, Becker KG, Prabhu V, Cooke DW (2008) Adipocyte gene expression is altered in formerly obese mice and as a function of diet composition. J Nutr 138(6):1033–1038

    Article  CAS  Google Scholar 

  6. Fujiki K, Kano F, Shiota K, Murata M (2009) Expression of the peroxisome proliferator activated receptor γ gene is repressed by DNA methylation in visceral adipose tissue of mouse models of diabetes. BMC Biol 7:38

    Article  Google Scholar 

  7. Kondo Y, Shen L, Issa J-P (2018) Role of DNA methylation in in tumor suppressor gene silencing in colorectal cancer. Anna of Can Ther and Pharm 1:001–008

    Google Scholar 

  8. Mirza S, Sharma G, Parshad R, Gupta SD, Pandya P, Ralhan R (2013) Expression of DNA methyltransferases in breast cancer patients and to analyze the effect of natural compounds on DNA methyltransferases and associated proteins. J Breast Cancer 16:23–31

    Article  Google Scholar 

  9. Park JB, Velasquez MT (2012) Potential effects of lignan-enriched flaxseed powder on bodyweight, visceral fat, lipid profile, and blood pressure in rats. Fitoterapia 83:941–946

    Article  CAS  Google Scholar 

  10. Rhee Y, Brunt A (2011) Flaxseed supplementation improved insulin resistance in obese glucose intolerant people: a randomized crossover design. Nutr J 10:44

    Article  CAS  Google Scholar 

  11. Zhang W, Xu S (2007) Microwave assisted extraction of secoisolariciresinol diglucoside from flaxseed hull. J Sci Food Agric 87:1455–1462

    Article  CAS  Google Scholar 

  12. Fukumitsu S, Aida K, Ueno N, Ozawa S, Takahashi Y, Kobori M (2008) Flaxseed lignan attenuates high-fat diet-induced fat accumulation and induces adiponectin expression in mice. Br J Nutr 100:669–676

    Article  CAS  Google Scholar 

  13. Popa VM, Gruia A, Raba DN, Dumbrava D, Moldovan C, Bordean D et al (2012) Fatty acids composition and oil characteristics of linseed (Linum usitatissimum L.) from Romania. J Agroaliment Processes Technol 18:136–140

    Google Scholar 

  14. Baranowski M, Enns J, Blewett H, Yakandawala U, Zahradka P, Taylor CG (2012) Dietary flaxseed oil reduces adipocyte size, adipose monocyte chemoattractant protein-1 levels and T-cell infiltration in obese, insulin-resistant rats. Cytokine 59:382–391

    Article  CAS  Google Scholar 

  15. El-Shobaki FA, Mohamed S, Abd-El-Azeem AS, Hegazy AM (2013) Comparative study to evaluate the role of flaxseed oil to alleviate complications due to consumption of high fat and carbohydrate diet. J Appl Sci Res 9:3167–3173

    CAS  Google Scholar 

  16. Campos AC, Molognoni F, Melo FH, Galdieri LC, Carneiro CR, D’Almeida V et al (2007) Oxidative stress modulates DNA methylation during melanocyte anchorage blockade associated with malignant transformation. Neoplasia 9(12):1111–1121

    Article  CAS  Google Scholar 

  17. Ferre P (2004) The biology of peroxisome proliferator–activated receptors: relationship with lipid metabolism and insulin sensitivity. Diabetes 53(S1):S43–S50

    Article  CAS  Google Scholar 

  18. Guerre-Millo M, Gervois P, Raspé E, Madsen L, Poulain P, Derudas B, Herbert JM, Winegar DA, Willson TM, Fruchart JC, Berge RK, Staels B (2000) Peroxisome proliferator-activated receptor α activators improve insulin sensitivity and reduce adiposity. J Biol Chem 275(22):16638–16642

    Article  CAS  Google Scholar 

  19. Lefebvre P, Chinetti G, Fruchart JC, Staels B (2006) Sorting out the roles of PPARα in energy metabolism and vascular homeostasis. J Clin Invest 116(3):571–580

    Article  CAS  Google Scholar 

  20. Ye J, Doyle PJ, Iglesias MA, Watson DG, Cooney GJ, Kraegen EW (2001) Peroxisome proliferator activated receptor (PPAR)-α activation lowers muscle lipids and improves insulin sensitivity in high fat fed rats comparison with PPAR-γ activation. Diabetes 50(2):411–417

    Article  CAS  Google Scholar 

  21. Pichiah PB, Moon HJ, Park JE, Moon YJ, Cha YS (2012) Ethanolic extract of seabuckthorn (Hippophae rhamnoides L) prevents high-fat diet-induced obesity in mice through down-regulation of adipogenic and lipogenic gene expression. Nutr Res 32:856–864

    Article  CAS  Google Scholar 

  22. Lee SE, Lee EH, Lee TJ, Kim SW, Kim BH (2013) Anti-obesity effect and action mechanism of Adenophora triphylla root ethanol extract in C57BL/6 obese mice fed a high-fat diet. Biosci Biotechnol Biochem 77(3):544–550

    Article  CAS  Google Scholar 

  23. Lillycrop KA, Phillips ES, Torrens C, Hanson MA, Jackson AA, Burdge GC (2008) Feeding pregnant rats a protein-restricted diet persistently alters the methylation of specific cytosines in the hepatic PPAR alpha promoter of the offspring. Br J Nutr 100(2):278–282

    Article  CAS  Google Scholar 

  24. Meiera U, Gressner AM (2004) Endocrine regulation of energy metabolism: review of pathobiochemical and clinical chemical aspects of leptin, ghrelin, adiponectin, and resistin. Clin Chem 50(9):1511–1525

    Article  Google Scholar 

  25. Boque N, Iglesia R, Garza AL, Milagro FI, Olivares M, Bañuelos O et al (2013) Prevention of diet-induced obesity by apple polyphenols in Wistar rats through regulation of adipocyte gene expression and DNA methylation patterns. Mol Nutr Food Res 57(8):1473–1478

    Article  CAS  Google Scholar 

  26. Milagro F, Campión J, García-Díaz D, Goyenechea E, Paternain L, Martínez J (2009) High fat diet-induced obesity modifies the methylation pattern of leptin promoter in rats. J Physiol Biochem 65(1):1–10

    Article  CAS  Google Scholar 

  27. Uriarte G, Paternain L, Milagro FI, Martinez JA, Campion J (2013) Shifting to a control diet after a high-fat, high-sucrose diet intake induces epigenetic changes in retroperitoneal adipocytes of Wistar rats. J Physiol Biochem 69:601–611

    Article  CAS  Google Scholar 

  28. Tominaga S, Nishi K, Nishimoto S, Akiyama K, Yamauchi S, Sugahara T (2012) (—)-Secoisolariciresinol attenuates high-fat diet-induced obesity in C57BL/6 mice. Food Funct 3:76–82

    Article  CAS  Google Scholar 

  29. Schmitten TD, Livak KJ (2008) Analyzing real-time PCR data by the comparative CT method. Nat Protoc 3:1101–1108

    Article  Google Scholar 

  30. Steibel J, Poletto R, Coussens P, Rosa G (2009) A powerful and flexible linear mixed model framework for the analysis of relative quantification RT-PCR data. Genomics 94:146–152

    Article  CAS  Google Scholar 

  31. The Jaxson Laboratory (n.a) Aged C57BL/6J mice for research studies: considerations, applications, and best practices. https://www.jax.org/jax-mice-and-services/customer-support/manuals-posters-and-guides/jmcrs-manuals-guides/aged-b6-whitepaper. Accessed 16 Apr 2020

  32. Niculescu M, Lupu D, Craciunescu C (2013) Perinatal manipulation of α-linolenic acid intake induces epigenetic changes in maternal and offspring livers. FASEB J 27:350–358

    Article  CAS  Google Scholar 

  33. Rhee Y (2016) Flaxseed secoisolariciresinol diglucoside and enterolactone down-regulated epigenetic modification associated gene expression in murine adipocytes. J Funct Food 23:523–531

    Article  CAS  Google Scholar 

  34. Weisenborn D, Tostenson K, Kangas N (2003) Continuous abrasive method for mechanically fractionating flaxseed. J Am Oil Chem Soc 80:295–300

    Article  Google Scholar 

  35. Madhusudhan B, Wiesenborn D, Schwarz J, Tostenson K, Gillespie J (2000) A dry mechanical method for concentrating the lignan secoisolariciresinol diglucoside in flaxseed. Lebensm WissTechnol 33:268–275

    Article  CAS  Google Scholar 

Download references

Acknowledgements

The authors thank Curt Doetkott and Qian Wen for the assistance with statistical analysis and Drs. Katie Reindl and Shireen Chikara for assistance in RT-qPCR techniques.

Author information

Authors and Affiliations

  1. Department of Health, Nutrition, and Exercise Sciences, North Dakota State University, Fargo, ND, USA

    A. Evenocheck & Y. Rhee

  2. Department of Dairy and Food Science, South Dakota State University, Brookings, SD, USA

    C. Hall

Authors
  1. A. Evenocheck
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Y. Rhee
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. C. Hall
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Y. Rhee.

Ethics declarations

Conflict of Interest

The authors declare that there are no conflicts of interests. This study was supported by grants from North Dakota State University College of Human Sciences and Education and the Department of Health, Nutrition, and Exercise Sciences.

Additional information

Publisher’s Note

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

Electronic supplementary material

ESM 1

(DOCX 44 kb)

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Evenocheck, A., Rhee, Y. & Hall, C. Do Health Promoting Compounds of Flaxseed Attenuate Weight Gain Via Modulation of Obesity Gene Expression?. Plant Foods Hum Nutr 75, 441–445 (2020). https://doi.org/10.1007/s11130-020-00825-z

Download citation

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s11130-020-00825-z

Keywords

Search

Navigation