TRAMP Prostate Tumor Growth Is Slowed by Walnut Diets Through Altered IGF-1 Levels, Energy Pathways, and Cholesterol Metabolism

Abstract

Dietary changes could potentially reduce prostate cancer morbidity and mortality. Transgenic adenocarcinoma of the mouse prostate (TRAMP) prostate tumor responses to a 100 g of fat/kg diet (whole walnuts, walnut oil, and other oils; balanced for macronutrients, tocopherols [a-and c]) for 18 weeks ad libitum were assessed. TRAMP mice (n = 17 per group) were fed diets with 100 g fat from either whole walnuts (diet group WW), walnut-like fat (diet group WLF, oils blended to match walnut's fatty acid profile), or as walnut oil (diet group WO, pressed from the same walnuts as WW). Fasted plasma glucose was from tail vein blood, blood was obtained by cardiac puncture, and plasma stored frozen until analysis. Prostate (genitourinary intact [GUI]) was weighed and stored frozen at -80°C. Plasma triglyceride, lipoprotein cholesterol, plasma multianalyte levels (Myriad RBM Rat Metabolic MAP), prostate (GUI), tissue metabolites (Metabolon, Inc., Durham, NC, USA), and mRNA (by Illumina NGS) were determined. The prostate tumor size, plasma insulin-like growth factor-1 (IGF-1), high density lipoprotein, and total cholesterol all decreased significantly (P < .05) in both WW and WO compared to WLF. Both WW and WO versus WLF showed increased insulin sensitivity (Homeostasis Model Assessment [HOMA]), and tissue metabolomics found reduced glucose-6-phosphate, succinylcarnitine, and 4-hydroxybutyrate in these groups suggesting effects on cellular energy status. Tissue mRNA levels also showed changes suggestive of altered glucose metabolism with WW and WO diet groups having increased PCK1 and CIDEC mRNA expression, known for their roles in gluconeogenesis and increased insulin sensitivity, respectively. WW and WO group tissues also had increased MSMB mRNa a tumor suppressor and decreased COX-2 mRNA, both reported to inhibit prostate tumor growth. Walnuts reduced prostate tumor growth by affecting energy metabolism along with decreased plasma IGF-1 and cholesterol. These effects are not due to the walnut's N-3 fatty acids, but due to component(s) found in the walnut's fat component.KEY WORDS: chemoprevention fat insulin-like growth factor 1 prostate cancer transgenic adenocarcinoma of the mouse prostate model walnut whole foods

Nut consumption and risk of cardiovascular disease, total cancer, all-cause and cause-specific mortality: a systematic review and dose-response meta-analysis of prospective studies

“…Oxidative damage and insulin resistance are important pathogenic drivers of cancer [67, 68] and a number of specific causes of death [69]. Nuts and seeds and particularly walnuts, pecans, and sunflower seeds have a high antioxidant content [70], and could prevent cancer by reducing oxidative DNA damage [9], cell proliferation [71, 72], inflammation [73, 74], and circulating insulin-like growth factor 1 concentrations [75] and by inducing apoptosis [71], suppressing angiogenesis [76], and altering the gut microbiota [77]. Although nuts are high in total fat, they have been associated with lower weight gain [78–80] and lower risk of overweight and obesity [79] in observational studies and some randomized controlled trials [80].…”

Effects of Walnut Consumption on Colon Carcinogenesis and Microbial Community Structure

“…Walnuts may be a particularly attractive whole food approach for cancer prevention. They are readily available, widely consumed, and contain an excellent profile of bioactive components that may exert complex and synergistic effects on tumorigenesis (16,22,(24)(25)(26)(27)(28)(29)(30).…”

Fat intake after prostate cancer diagnosis and mortality in the Physicians’ Health Study

“…It is possible that the observed benefit of vegetable fat may be due to some other nutrient(s) or phytochemical(s) in food sources of vegetable fat. In a mouse model of prostate cancer, mice fed 100g fat from whole walnuts or walnut oil had smaller prostate tumors compared to mice fed 100g of fat blended to match the fatty acid profile of walnuts (15). This supports the hypothesis that the benefit of vegetable fats may be driven by compound(s) in the fat component of food sources of vegetable fat, rather than the fatty acids themselves.…”

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