|DAVIS, PAUL - University Of California|
|VASU, VIHAS - University Of California|
|GOHIL, KISHORCHANDRA - University Of California|
|KHAN, IMRAN - University Of California|
|CROSS, CARROLL - University Of California|
|Yokoyama, Wallace - Wally|
Submitted to: British Journal of Nutrition
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 12/7/2011
Publication Date: 1/16/2012
Citation: Davis, P.A., Vasu, V., Gohil, K., Kim, H., Khan, I., Cross, C., Yokoyama, W.H. 2012. A high-fat diet containing whole walnuts (Juglans regia) reduces tumour size and growth along with plasma insulin-like growth factor 1 in the transgenic adenocarcinoma of the mouse prostate model. British Journal of Nutrition. 00:1-9. DOI: 10.1017/S0007114511007288.
Interpretive Summary: Walnuts suppressed the growth rate of tumors in a mouse model of prostate cancer compared to a diet with the same high level of fat and fatty acid composition. Prostate tumor growth was also slower on a low fat diet. Insulin growth factor-1 (IGF-1) a protein associated with increased tumor growth was lower in animals fed the walnut diet. An analysis of a broad range of biochemicals, metabolomics, found that cholesterol, glycerolipid, and sphingolipid metabolism was modified by the walnut diet compared to the control high fat diet. The results show that high fat alone is not a cause of increased tumor growth.
Technical Abstract: Dietary fat is linked to prostate cancer (PCa), the most commonly diagnosed male cancer, but the nature and strength of the relationships between total fat, n-6 and n-3 fatty acids and PCa remain incompletely understood. Transgenic adenocarcinoma of the mouse prostate (TRAMP) mice (N=10-12 per group) at 8 weeks old were fed ad lib three semisynthetic diets with similar fatty acid speciation: 2 moderately high fat diets (28% as energy (EN)) containing either whole walnuts (WW) or soybean oil (HF) or a lowfat (LF) 12% as EN from soybean oil. Prostates were harvested after 9, 18 and 24 weeks. At 18 weeks, WW animal whole prostate weight (1.28±0.1 g) was lower versus HF mice (2.59 ± 0.7 g) and had reduced plasma IGF-1 (WW 58699±6556 pg/dL vs. 84363±7571) HF, PAI-1 (1.7±0.6 vs. 3.8 ±0.6 (HF)) and LDL cholesterol (14.1 ±5.8 mg/dL) versus HF (25.5 ±12.7 mg/dL); all p<0.05 compared to HF). Prostate growth rate declined (-3± 2%/wk, p<0.015) in both WW and LF groups compared to HF growth rate (11 ± 3 %/week) while WW and HF whole animal growth was equivalent but reduced in LF (p<0.001). Liver metabolomic analysis found WW altered hepatic glucose, oxidative stress as well as glycerolipid, sphingolipid and cholesterol metabolism. The results suggest that walnuts may act via a combination of effects on growth related systems such as IGF-1, sphingolipid and cholesterol. Total dietary fat content did not predict prostate tumor response strengthening the case that it is unlikely that PCa risk is linked to a single nutrient or set of nutrients.