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Neha Rai
Introduction
Most of us think that obesity increases the risk of breast cancer, and we try different kinds of diets to reduce the risk of cancer. But how obesity speeds up tumor growth is still a mystery. A recent study published in Cancer and Metabolism is challenging the old belief that losing weight can slow cancer growth.
In the study titled ‘Hyperlipidemia drives tumor growth in a mouse model of obesity-accelerated breast cancer growth,’ researchers found that high blood lipid levels alone can drive breast cancer growth. So, if a person with cancer is losing weight, but the lipid levels are not reduced, the tumor might still grow.
This article explores how reduced lipid levels can mitigate the risk of breast cancer and how understanding lipid metabolism could lead to new ways to prevent and treat breast cancer.
Why Lipids Matter in Cancer Growth
When cancer cells break away from their original location and spread (metastasis), they face several challenges. To overcome these challenges, they often exploit lipid metabolism. Lipid uptake and storage provide cancer cells with energy and building blocks as they spread to other parts of the body.
Metastatic cancer cells alter the composition of their lipid membrane and produce lipid intermediates to tolerate the oxidative environment when they try to break away from the original tumor and spread. Moreover, changes in lipid metabolism in the primary tumor can also help them evade immune cell surveillance.
There are two main pathways by which tumors acquire lipids:
- De novo lipogenesis, where the sugars are converted into fats to make the building blocks for new cells.
- Exogenous lipid uptake, where the tumor cells use the fat from the surroundings to get energy and building blocks for their growth and survival.1
The study explores the role of lipids in the growth of cancer and opens new avenues for cancer research.
How the Study Was Done
Researchers used two breast cancer models (E0771 and Py230) in female C57BL/6 mice and ApoE and LDL receptor knockout mice to test several conditions. They showed that high lipid levels alone can trigger and speed up breast cancer growth.
Diet-induced Obesity
To study the diverse roles of dietary lipids on breast cancer growth, researchers fed young female mice either a high- or a low-fat diet over several weeks, followed by injection of breast cancer cells into their mammary fat pads.
Mice on the high-fat diet gained more body fat and showed higher levels of blood sugar, insulin, triglycerides, cholesterol, and fatty acids. Breast tumors grew faster and larger in the mice that became obese, indicating that obesity and higher blood lipids can speed up breast cancer growth.
Genetic hyperlipidemia
To explore how high blood lipids alone can affect breast cancer growth, two knockout mice (ApoE and LDL receptor knockout) were used, which have impaired ability to clear cholesterol from the body. They were then fed a diet that causes high levels of triglycerides and cholesterol, followed by the injection of breast cancer cells.
Tumors grew much faster and larger in the knockout mice compared to the normal mice, even though their body weight, fat mass, and glucose levels were similar. The results showed that high blood lipids alone can speed up breast cancer growth, regardless of the presence of obesity or altered metabolic factors.
Ketogenic diet-induced hyperlipidemia
The researchers also looked at whether high blood lipids caused by diet could make breast cancer grow faster, even without high blood sugar or insulin. Mice were fed either a 90% fat ketogenic diet (KD) or a low-fat diet, followed by injection of breast cancer cells.
Mice on a ketogenic diet had high levels of triglycerides and cholesterol but normal blood sugar and insulin levels. However, the tumors grew twice the size in mice who had KD compared to the low-fat group. Tests also showed that the cancer cells took up more lipids from the blood when fed on KD. This shows that high blood lipids alone, without obesity or high insulin, can speed up breast cancer progression.
Lipid-lowering therapy
Researchers wanted to test whether lowering blood lipids could stop obesity-driven tumor growth. Obese and lean mice were put into treatment with similar starting lipid levels and were then treated with antisense oligonucleotides (ASOs) to reduce the level of triglyceride and glycerol. This was followed by injecting the breast cancer cells to assess tumor growth.
ASO lowered blood triglycerides and cholesterol in both lean and obese mice. Body weight and fat mass did not change with ASO treatment. Lowering lipids slowed tumor growth in obese mice but not in lean mice. The results show that lowering lipid levels is sufficient to reduce the tumors in obese mice.
Weight loss without lowering lipid levels
To study how metabolic state affects obesity-driven breast cancer, researchers compared tumor growth in obese and formerly obese mice on a high-fat diet followed by two weight-loss diets: a ketogenic diet (KD) or a low-fat diet (LFD). Control mice stayed on LFD the whole time.
Interestingly, mice that switched to a low-fat diet had smaller tumors, but mice that switched to a ketogenic diet had tumor sizes similar to obese mice, even though they were leaner and had better blood sugar control.2
Key Findings
High lipid levels are enough on their own to speed up breast cancer growth.
The study found that high blood lipids (hyperlipidemia) by themselves can speed up breast cancer growth in mice, even when there is no obesity, high insulin, or high glucose. This means that high lipid levels during obesity are important in breast cancer progression. Most studies on obesity and cancer focus on problems with glucose, but this research shows that lowering blood lipids can slow tumor growth even if obesity stays the same.
Tumors in this situation may not respond as well to treatments that block their lipid production, but may be more sensitive to treatments that lower lipid levels in the body. Since about half of new breast cancer patients are obese, lowering high blood lipids could be an important way to treat the disease.
Lipids help tumors get the energy they need
Lipids provide cancer cells with the materials and energy they need to grow. Many tumors change how they use and make fats. Breast cancer cells exposed to high levels of lipids take in more fats, but it is still unclear how they use these fats in the body. In this study, the breast cancer cells used absorbed both free fatty acids and lipoproteins, which suggests they have several ways to take in lipids.
Since lipids come in many forms, and each type affects cells and immunity differently, cancer cells may use several kinds of lipids, such as triglycerides, free fatty acids, and sterols, to help them grow. In this study, three different high-fat diets, even though they had different amounts of fat, led to similar results, probably because they contained similar types of fatty acids.
The Ketogenic Diet Paradox
The ketogenic diet is often recommended for weight loss and sometimes as a supportive option during cancer treatment. Losing weight after breast cancer treatment can help, but not all weight-loss diets improve metabolic health in the same way. KD lowers glucose and insulin, which may benefit cancers that rely on these fuels, such as many brain tumors or those with PI3K/Akt mutations. However, results in other cancers vary: KD can slow down or speed up the tumor growth or even have no effect on the tumor.
In people with obesity, cancer cells might adapt to use fats directly for growth, so a KD that is usually high in fats could help the tumor grow. In summary, how well KD works as a cancer therapy depends on the type of tumor, genetics, and the patient’s metabolic health. Nutrition plans should also consider assessing how much the cancer depends on fats.2
Limitations and Future Research
C57BL/6 mice that were used in this study are often chosen for diet-induced obesity studies because they gain weight easily on a high-fat diet. In contrast, immunocompromised nude mice are used for human cancer research, and they do not gain weight so easily. As a result, there are not many good models for studying obesity-driven breast cancer, and it is uncertain if findings apply to hormone receptor-positive breast cancer.
This mouse model helps researchers study tumors in a metabolically unhealthy but immunocompetent host. However, the cancer cells themselves do not grow in a changed metabolic state, so it is difficult to understand how tumors adapt their metabolism, especially during quick weight loss.
Lowering blood lipids slowed tumor growth in the study, but it is not clear if people taking medications such as statins or GLP-1 agonists would have the same effect. The study also does not show which lipids are responsible for tumor growth.2
The research is promising and opens up new areas to explore in cancer research and new treatment targets. However, more research is needed to find out how cancer cells take in and use fats.
Takeaway
- High blood lipid levels, and not just obesity or high blood sugar, can help breast cancer grow.
- Tumors use fat for energy and to build new cells. Lowering blood lipid levels can slow tumor growth, even if there is no weight loss.
- Lowering high blood lipids could be an important way to prevent or treat breast cancer, especially for people with obesity.
- Not all weight-loss diets work the same way. For example, diets like the ketogenic diet may lower glucose but can raise lipid levels, which might help tumors grow.
- Understanding how cancer cells use fats and looking at a patient’s overall metabolic health could help create better, more personalized cancer treatments and prevention plans.
Header Image Source:
Edited by Karli Norville
References
- Martin-Perez, M., Urdiroz-Urricelqui, U., Bigas, C., & Benitah, S. A. (2022). The role of lipids in cancer progression and metastasis. Cell Metabolism, 34(11), 1675–1699. https://doi.org/10.1016/j.cmet.2022.09.023
- Vieira, R. F., Sanchez, S. R., Arumugam, M., Mower, P. D., Curtin, M. C., Jackson, A. E., Gallop, M. R., Wright, J., Bowles, A., Ducker, G. S., Hilgendorf, K. I., & Chaix, A. (2025). Hyperlipidemia drives tumor growth in a mouse model of obesity-accelerated breast cancer growth. Cancer & Metabolism, 13(1), 39. https://doi.org/10.1186/s40170-025-00407-0
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