Long-Chain Omega-3 Polyunsaturated Fatty Acids Modulate Mammary Gland Composition and Inflammation

  • Saraswoti Khadge
  • Geoffrey M. Thiele
  • John Graham Sharp
  • Timothy R. McGuire
  • Lynell W. Klassen
  • Paul N. Black
  • Concetta C. DiRusso
  • James E. Talmadge


Studies in rodents have shown that dietary modifications as mammary glands (MG) develop, regulates susceptibility to mammary tumor initiation. However, the effects of dietary PUFA composition on MGs in adult life, remains poorly understood. This study investigated morphological alterations and inflammatory microenvironments in the MGs of adult mice fed isocaloric and isolipidic liquid diets with varying compositions of omega (ω)-6 and long-chain (Lc)-ω3FA that were pair-fed. Despite similar consumption levels of the diets, mice fed the ω-3 diet had significantly lower body-weight gains, and abdominal-fat and mammary fat pad (MFP) weights. Fatty acid analysis showed significantly higher levels of Lc-ω-3FAs in the MFPs of mice on the ω-3 diet, while in the MFPs from the ω-6 group, Lc-ω-3FAs were undetectable. Our study revealed that MGs from ω-3 group had a significantly lower ductal end-point density, branching density, an absence of ductal sprouts, a thinner ductal stroma, fewer proliferating epithelial cells and a lower transcription levels of estrogen receptor 1 and amphiregulin. An analysis of the MFP and abdominal-fat showed significantly smaller adipocytes in the ω-3 group, which was accompanied by lower transcription levels of leptin, IGF1, and IGF1R. Further, MFPs from the ω-3 group had significantly decreased numbers and sizes of crown-like-structures (CLS), F4/80+ macrophages and decreased expression of proinflammatory mediators including Ptgs2, IL6, CCL2, TNFα, NFκB, and IFNγ. Together, these results support dietary Lc-ω-3FA regulation of MG structure and density and adipose tissue inflammation with the potential for dietary Lc-ω-3FA to decrease the risk of mammary gland tumor formation.


Diet PUFA Omega-3 Mammary gland Fish oil Mammary gland-density 



Arachidonic acid


Docosahexaenoic acid


Eicosapentaenoic acid


Fatty acid


Insulin like growth factor




Mammary fat pad


Mammary gland


Monounsaturated fatty acid


Polyunsaturated fatty acid


Quantitative real-time polymerase chain reaction


Saturated Fatty Acid


Specific pathogen free


Terminal end bud


Compliance with Ethical Standards

Conflict of Interest

The authors declare that there are no conflicts of interest.


We gratefully acknowledge funding from the Fred & Pamela Buffett Cancer Center’s NIH Cancer Center Support Grant (P30CA036727) for this project. Also, funding from the UNMC College of Medicine (LWK) Endowed Chair.


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  • Saraswoti Khadge
    • 1
  • Geoffrey M. Thiele
    • 1
    • 2
    • 3
  • John Graham Sharp
    • 4
  • Timothy R. McGuire
    • 5
  • Lynell W. Klassen
    • 2
    • 3
  • Paul N. Black
    • 6
  • Concetta C. DiRusso
    • 6
  • James E. Talmadge
    • 1
    • 2
  1. 1.Department of Pathology and MicrobiologyUniversity of Nebraska Medical CenterOmahaUSA
  2. 2.Department of Internal MedicineUniversity of Nebraska Medical CenterOmahaUSA
  3. 3.Veteran Affairs Nebraska-Western Iowa Health Care SystemOmahaUSA
  4. 4.Department of Genetics, Cell Biology and AnatomyUniversity of Nebraska Medical CenterOmahaUSA
  5. 5.Department of Pharmacy PracticeUniversity of Nebraska Medical CenterOmahaUSA
  6. 6.Department of BiochemistryUniversity of Nebraska-LincolnLincolnUSA

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