Researchers at the Huntsman Cancer Institute discovered that lean fat cells produce a protective lipid called 9S-HODE that restrains breast cancer growth through ferroptosis. This protective molecule is less present with obesity, revealing a possible reason why obesity is a risk factor for breast cancer.
Medical researchers have uncovered a biological mechanism linking obesity to cancer risk, finding that obesity prevents a biological process that kills cancerous cells. The transformative findings, published in the journal Science, focus on how different types of fat cells behave in lean versus obese bodies.
Breasts are mostly composed of fat, particularly fat cells called adipocytes. Depending on a person’s weight, these adipocytes can be lean or obese, and they generate distinctive microenvironments for cancer cells.
How Lean Fat Cells Fight Breast Cancer
Working with preclinical models and breast tissues from donors, a research team at the Huntsman Cancer Institute at the University of Utah identified a key difference in lean tissue. Lean adipocytes produce much more of a lipid, or fatty acid, known as 9S-HODE than obese ones.
We uncovered the role of a molecule that normally appears in lean tissue that restrains breast cancer growth but is less present with obesity,
This lipid plays an important role in promoting cell death, particularly a kind of cell death called ferroptosis. This is one way the body purges old and damaged cells, including cells that could be cancerous. Because lean adipocytes produce more 9S-HODE, cancerous cells die more readily in lean tissue.
We found that the lean adipocytes produce much more 9S-HODE than obese ones. This means that cancerous cells die more readily in lean tissue,
The Missing Defense in Obesity
Obesity has been linked to an increased risk of breast cancer through changes in hormone levels, increased inflammation and oxidative stress, and insulin resistance. Higher levels of oestrogen and insulin resistance are risk factors that can promote cell growth and division, leading to an increased risk of cancer, including aggressive forms like triple-negative breast cancer.
However, this new research considers how obesity could also be the loss of something that naturally protects us.
We know obesity is often a driver of breast cancer, and researchers in our field usually consider how obesity is promoting the disease. But we hadn't really considered that obesity could also be the loss of something that naturally protects us,
In obesity, adipocytes are larger than in their lean counterparts and produce less 9S-HODE. Without this chemical signal, the body loses a way it actively protects us under lean circumstances.
Restoring Protection Through Therapeutics
In preclinical mouse models, the research team found that increasing the amount of 9S-HODE in obese adipocytes suppressed breast cancer tumor growth. This discovery suggests a possible therapeutic approach to slow breast cancer growth by restoring this protection.
From a clinical perspective, this discovery is incredibly empowering. Because 9S-HODE is naturally present in the body but is lost with obesity, we may be able to restore this protection by putting it back. That could become a very feasible therapeutic approach to slow breast cancer growth,
While investigators emphasize that obesity is just one factor that contributes to breast cancer and that the disease can develop for other reasons, the findings point toward harnessing what our bodies are already doing.
Practical Risk Reduction While Science Advances
Maintaining a healthy weight may reduce the risk of developing breast cancer. Guidance suggests maintaining a healthy, balanced diet including fruits, vegetables, whole grains, and lean proteins while limiting processed foods, sugary drinks, high-fat foods, and alcohol consumption.
Additional lifestyle modifications include engaging in at least 30 minutes of moderate-intensity exercise daily, managing stress, ensuring 7-8 hours of sleep per night, and staying up-to-date with breast cancer screenings such as mammograms and clinical breast exams for early detection.
