Obesity has long been recognized as a risk factor for breast cancer. However, a recent study published in Cancer & Metabolism (2025) challenges a fundamental assumption regarding the underlying mechanisms. The findings have significant implications for approaches to diet, weight management, and cancer prevention.
The key finding suggests that excess body fat may not be the primary driver of tumor growth; instead, circulating blood lipids may play a more critical role.
Researchers found that elevated blood lipids, including high triglycerides and cholesterol, were both sufficient and necessary to accelerate breast cancer growth in mice, even in the absence of obesity and with normal blood glucose and insulin levels.
What the study looked at
Scientists at the University of Utah employed two established mouse models of triple-negative breast cancer (E0771 and Py230) to distinguish the effects of obesity from those of specific metabolic alterations commonly associated with it.
Instead of merely comparing lean and obese mice, the researchers utilized genetic models (mice lacking ApoE or the LDL receptor) that develop hyperlipidemia, characterized by elevated blood lipid levels without obesity. Additionally, a ketogenic diet was employed, known to significantly increase lipid levels while maintaining low blood glucose levels.
Tumors were three times larger in obese mice than in lean mice after 3 weeks.
Py230 tumors were five times larger in mice fed a high-fat diet compared to those on a low-fat diet.
Genetically hyperlipidemic mice developed tumors twice as large as those in normal mice.
Pharmacological reduction of blood lipids in obese mice resulted in a 1.6-fold decrease in tumor size.
Elevated blood lipid levels promote tumor growth, independent of obesity.
This is the most striking result: when researchers induced high blood lipid levels in non-obese mice with normal glucose and insulin levels, tumors still grew significantly faster than in mice with normal lipid levels. This directly shows that elevated blood cholesterol and triglycerides, not simply being overweight, can feed tumor growth.
Conversely, when researchers pharmacologically lowered blood lipid levels in obese mice using an antisense oligonucleotide targeting the liver protein Angptl3, tumor growth slowed despite persistent obesity. Thus, reducing blood lipid levels limited the tumor’s energy supply without necessitating weight loss.
Why does this happen? Tumors eat fat
Cancer cells exhibit a high demand for lipids, utilizing fats for membrane synthesis during proliferation, as an energy source, and as a buffer against nutrient scarcity within the tumor microenvironment. Elevated blood lipid levels increase the availability of these resources for tumor uptake.
The study confirmed that breast cancer cells in hyperlipidemic mice absorbed significantly more dietary fat than those in normal mice. In laboratory experiments, these cells readily took up both free fatty acids and LDL particles (the “bad cholesterol” carrier). Notably, this uptake occurred via macropinocytosis, rather than through the commonly discussed CD36 fatty acid transporter.
Implications of the ketogenic diet
A particularly important and counterintuitive result concerns the ketogenic diet (KD), which is widely used for weight loss and is increasingly considered as an adjuvant cancer therapy due to its ability to suppress glucose and insulin, metabolic factors on which some cancer types depend.
In this study, obese mice that switched to a ketogenic diet lost weight and had normal blood sugar and insulin levels, but their blood fats (triglycerides, cholesterol, and free fatty acids) remained very high. In some cases, these levels were even higher than in obese mice that stayed on a high-fat diet.
As a result, mice on the ketogenic diet, even though they were leaner and had better blood sugar, had tumors just as large as obese mice on a high-fat diet. In contrast, mice switched to a standard low-fat diet, which lowered both body fat and blood fats, and had much smaller tumors.
This does not mean the ketogenic diet is always harmful for cancer. Studies show it can help treat cancers that depend on glucose, such as some brain tumors and PI3K-mutant cancers. But for obesity-related breast cancer, this study suggests the KD might actually give tumors more fat to use, which is the opposite of what is intended.
What this means for you
This research was conducted in mice and focused on triple-negative breast cancer cells. So, the results may not apply to all types of breast cancer. Human studies are still needed. Still, these findings are important to think about, especially for people dealing with both obesity and breast cancer risk.
The key takeaways are:
Blood fat levels are important, not just body weight. If you are trying to lower your cancer risk, monitoring triglycerides and cholesterol may be just as important as watching your BMI.
Not all weight loss methods are the same. Approaches that also lower blood fats, like a standard low-fat or Mediterranean diet, may protect better against breast cancer coming back than those that do not, even if both help you lose the same amount of weight.
Medications that lower blood fats should be studied more in cancer research. Statins and similar drugs are already common for heart disease. This research suggests they might also help lower breast cancer risk or slow it down in people with obesity and high blood fats.
The ketogenic diet needs careful consideration in this situation. If you have obesity-related breast cancer, talk with your oncologist about how any diet affects your metabolism, not just your weight or blood sugar.
The bigger picture
Obesity is a risk factor for 13 types of cancer. In the United States, over 70% of adults are overweight or obese, and about half of new breast cancer patients have obesity. This research adds a new layer: obesity creates a body environment that helps cancer grow, and high blood fats seem to be a big part of that.
Targeting hyperlipidemia, lowering high blood fats, whether through diet, lifestyle changes, or medication, could become an important way to help prevent and control cancer, not just protect heart health.