A recent study published in Nature Communications found that breast tumors can actively strip nearby fat cells of their stored energy.
The researchers showed that in triple-negative and other aggressive breast cancers, tumor cells tap into nearby fat stores for energy. Microscopic imaging showed that cancer cells were actively triggering fat cells to break down their triglycerides into fatty acids, which the tumors then absorbed as fuel for growth.
Mechanism: breast tumors build direct “communication channels” with fat cells called gap junctions.
Through these tiny tunnels, the tumor sends signals, like the messenger molecule cAMP, that instruct fat cells to start burning through their reserves. The released fatty acids are then taken up by the tumor, giving cancer cells an external energy supply that allows them to continue growing and spreading even when their own metabolism is stressed.
This research is important because it changes how we understand aggressive cancers like triple-negative breast cancer.
For decades, the Warburg effect shaped cancer research. This idea comes from Otto Warburg’s observation that cancer cells prefer to rely on glucose and glycolysis rather than fully burning it in their mitochondria. Because of this, most cancer drugs were designed to cut off glucose supply or glycolysis.
But this new research shows cancer cells can pull fatty acids directly from nearby fat cells and gain a second energy stream that helps them survive when glucose is limited. If a tumor can switch to fat, drugs that only block glucose metabolism lose much of their effectiveness.
That flexibility helps tumors survive under stress and resist therapies. This research continues to prove that fatty acid metabolism is a major, and still underexplored, therapeutic target. It also explains, in part, why TNBC is so difficult to treat with current approaches.
How can we target lipolysis in triple negative breast cancer?
- Aspirin: Aspirin reduces lipolysis by inhibiting prostaglandin synthesis, an inflammatory signal that promotes fat breakdown. It also shifts cellular metabolism toward glucose oxidation, cutting off fatty acids as a backup energy source for tumors.
- Niacinamide: Niacinamide (vitamin B3) helps block lipolysis by lowering cAMP, the signal that tells fat cells to release fatty acids. With less cAMP, fat stays stored instead of being broken down.
- Magnesium: Magnesium helps calm the adrenal response, reducing the release of adrenaline. Since adrenaline is a key signal that triggers fat cells to release fatty acids, magnesium can blunt this effect and keep fat breakdown under better control.
- Decreasing dietary intake (especially PUFA): Lowering dietary polyunsaturated fats decreases the reservoir of fatty acids that tumors can exploit. PUFAs are particularly prone to oxidation and inflammation so the body stores them quickly. When they are released into circulation, they can be particularly damaging.
- Progesterone: Progesterone helps suppress chronic lipolysis, by opposing the effects of cortisol and adrenaline.