Excessive fats weight-reduction plan causes weight problems and impairs systemic metabolism, no matter dietary fats supply. Credit score: Nature Metabolism (2025). DOI: 10.1038/s42255-025-01330-w
Weight problems elevates the chance of a minimum of 13 main cancers, together with these of the breast, colon and liver. It additionally impairs immune responses that focus on tumors and are stimulated by most cancers immunotherapies. However it has lengthy been unclear whether or not these results stem from the sheer adiposity—or mass of fats—in individuals residing with weight problems or from the particular dietary fat they eat.
Now, a decade-long examine led by Ludwig Princeton’s Lydia Lynch and reported within the present subject of Nature Metabolism has supplied a compelling reply to that query.
“Our study reveals that the source of dietary fat, not adiposity itself, is the primary factor that influences tumor growth in obese mice,” stated Lynch. “We found that high-fat diets derived from lard, beef tallow or butter compromise anti-tumor immunity and accelerate tumor growth in several tumor models of obese mice. Diets based on coconut oil, palm oil or olive oil, meanwhile, do not have this effect in equally obese mice. Our findings have implications for cancer prevention and care for people struggling with obesity.”
Lynch and her colleagues—together with Marcia Haigis, a senior creator of the examine and a member of the Ludwig Heart at Harvard College—be aware that swapping out animal fat for plant fat could be a useful dietary intervention for overweight sufferers present process therapy for most cancers. Such dietary adjustments might additionally probably decrease most cancers danger for individuals residing with weight problems.
Lynch, Haigis and others have beforehand proven that weight problems induces adjustments within the immune system and within the microenvironment of tumors that contribute to tumor development. It does so by impairing the physique’s most cancers surveillance system, undermining the flexibility of immune cells—particularly cytotoxic T cells (CTLs) and pure killer (NK) cells—to infiltrate tumors and, as soon as there, kill their cancerous quarry.
Within the present examine, Lynch and her colleagues took these findings a step additional. They elucidate the mechanisms by which the metabolic derivatives of dietary animal fat impair NK cells and CTLs. Additionally they present that it’s this immune dysfunction that helps hasten tumor development in overweight mice—an impact not seen in overweight mice fed plant-based fat. In reality, a palm oil-based weight-reduction plan even boosted anti-tumor immunity and slowed tumor progress in overweight mice.
The researchers recognized a number of metabolic intermediates of dietary fat, particularly long-chain acylcarnitine species, that potently suppress NK cells and CTLs. These metabolites had been particularly elevated in overweight mice reared on butter, lard and beef tallow diets, however not in overweight mice on plant-fat diets. They report that in CTLs, the molecules trigger deep metabolic dysfunction in organelles generally known as mitochondria—the powerhouses of cells—compromising their cytotoxic perform. This saps anti-tumor CTLs of their vitality, undermines their manufacturing of an element (IFN-γ) vital to their perform and disables their cell-killing equipment.
The palm oil-based weight-reduction plan, alternatively, prevented metabolic paralysis within the NK cells of overweight mice, apparently by amplifying the exercise of a grasp regulator of mobile metabolism generally known as c-Myc. The researchers discovered that Myc expression was decreased in mice fed animal fats—and in addition in NK cells from individuals residing with weight problems.
“These findings highlight the significance of diet in maintaining a healthy immune system,” stated Lynch. “More importantly, they indicate that modifications to fat in the diet may improve outcomes in obese people undergoing treatment for cancer and suggest such measures should be clinically evaluated as a potential dietary intervention for such patients.”
Extra info:
Britta Kunkemoeller et al, The supply of dietary fats influences anti-tumour immunity in overweight mice, Nature Metabolism (2025). DOI: 10.1038/s42255-025-01330-w
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Ludwig Institute for Most cancers Analysis
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Examine finds animal-based fat gasoline tumor progress in overweight mice, plant fat don’t (2025, July 30)
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