1.
Common Variants in Lipid Metabolism-Related Genes Associate with Fat Mass Changes in Response to Dietary Monounsaturated Fatty Acids in Adults with Abdominal Obesity.
Hammad, SS, Eck, P, Sihag, J, Chen, X, Connelly, PW, Lamarche, B, Couture, P, Guay, V, Maltais-Giguère, J, West, SG, et al
The Journal of nutrition. 2019;(10):1749-1756
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Abstract
BACKGROUND Different fatty acids (FAs) can vary in their obesogenic effect, and genetic makeup can contribute to fat deposition in response to dietary FA composition. However, the antiobesogenic effects of the interactions between dietary MUFAs and genetics have scarcely been tested in intervention studies. OBJECTIVE We evaluated the overall (primary outcome) and genetically modulated (secondary outcome) response in body weight and fat mass to different levels of MUFA consumption. METHODS In the Canola Oil Multicenter Intervention Trial II, a randomized, crossover, isocaloric, controlled-feeding multicenter trial, 44 men and 71 women with a mean age of 44 y and an increased waist circumference (men ∼108 cm and women ∼102 cm) consumed each of 3 oils for 6 wk, separated by four 12-wk washout periods. Oils included 2 high-MUFA oils-conventional canola and high-oleic canola (<7% SFAs, >65% MUFAs)-and 1 low-MUFA/high-SFA oil blend (40.2% SFAs, 22.0% MUFAs). Body fat was measured using DXA. Five candidate single-nucleotide polymorphisms (SNPs) were genotyped using qualitative PCR. Data were analyzed using a repeated measures mixed model. RESULTS No significant differences were observed in adiposity measures following the consumption of either high-MUFA diet compared with the low-MUFA/high-SFA treatment. However, when stratified by genotype, 3 SNPs within lipoprotein lipase (LPL), adiponectin, and apoE genes influenced, separately, fat mass changes in response to treatment (n = 101). Mainly, the LPL rs13702-CC genotype was associated with lower visceral fat (high-MUFA: -216.2 ± 58.6 g; low-MUFA: 17.2 ± 81.1 g; P = 0.017) and android fat mass (high-MUFA: -267.3 ± 76.4 g; low-MUFA: -21.7 ± 102.2 g; P = 0.037) following average consumption of the 2 high-MUFA diets. CONCLUSIONS Common variants in LPL, adiponectin, and apoE genes modulated body fat mass response to dietary MUFAs in an isocaloric diet in adults with abdominal obesity. These findings might eventually help in developing personalized dietary recommendations for weight control. The trial was registered at clinicaltrials.gov as NCT02029833 (https://www.clinicaltrials.gov/ct2/show/NCT02029833?cond=NCT02029833&rank=1).
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Effect of lycopene on androgen receptor and prostate-specific antigen velocity.
Zhang, X, Wang, Q, Neil, B, Chen, X
Chinese medical journal. 2010;(16):2231-6
Abstract
BACKGROUND There is increasing interest in the role of dietary factors in both the development and behaviour of prostate cancer. This study was carried out to evaluate the impact of the dietary factor lycopene on DNA synthesis, activity and expression of the androgen receptor gene element in prostate LnCaP cells and to report our pilot phase II study investigating its effect on prostate-specific antigen velocity over one year. METHODS LnCaP cells were grown with or without different concentrations of lycopene or tetrahydrofuran (THF solvent) added to the culture medium for 48 hours. DNA synthesis was measured by the incorporation of bromodeoxyuridine (Brdu) into DNA during a 4-hour pulse, followed by immunostaining and visualization of stained cells using fluorescence microscopy. A transient transfection of a plasmid DNA recombinant containing an androgen receptor element-luciferase (ARE-Luc) report gene into LnCaP cells was developed and the impact of different concentrations of lycopene on the androgen receptor element was reflected by quantitative analysis of the luciferase enzyme function. Expression of the androgen gene was also studied by Western blotting. The phase II pilot study patients (n=41) previously diagnosed with prostate cancer were enrolled and given lycopene supplement, 10 mg per day, and response was measured by observing changes in the plasma prostate-specific antigen (PSA) levels. RESULTS The addition of 0.5 micromol/L, 5 micromol/L, 10 micromol/L and 15 micromol/L of lycopene was shown to inhibit cell growth by 2.66%, 4.29%, 3.73% and 13.66%, respectively, compared with the THF solvent control samples (P=0.015). As compared with the RPMI1640 medium group, cell proliferation in the presence of 5 micromol/L, 10 micromol/L, and 15 micromol/L lycopene was inhibited by 8.12%, 6.33% and 12.00%, respectively (P=0.024). We showed for the first time that lycopene inhibited the activity of the androgen receptor gene element in a dose-related manner. Inhibition was seen in the transcription of the luciferase construct and confirmed by androgen receptor element expression assayed by Western blotting. Regression slopes of (log) PSA vs. time decreased in 26/37 (70%, 95%CI 53%-84%) of the patients after supplementation and in eight cases (21%) the post-treatment slope was negative. For these eight patients, the average fall in PSA was equivalent to 2% over 28 days (i.e. an average slope/d of -0.000713). The Wilcoxon rank-sum test showed an overall statistically significant decrease in slope (P=0.0007). Analysis of the PSA doubling time (pretreatment vs. posttreatment) showed a median increase after supplementation for 174 days; however, this was not statistically significant (P=0.18). CONCLUSIONS Lycopene as an antioxidant dietary factor could significantly inhibit DNA synthesis in a dose-dependent pattern; the result revealed lycopene might inhibit androgen receptor gene element activity and expression. Dietary lycopene may play an important role in prostate cancer cell proliferation and further supports a large randomized study into the role of lycopene supplementation in malignant prostate disease.
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Structural basis for gene activation by p53 family members.
Scoumanne, A, Harms, KL, Chen, X
Cancer biology & therapy. 2005;(11):1178-85
Abstract
The p53 tumor suppressor is a modular transcription factor that determines cellular outcome (cell cycle arrest and DNA repair vs. apoptosis) in response to stress signals. The two p53 homologues, p63 and p73 play an important role in development but also act as tumor suppressors. The p53 family members are highly homologous in the activation domain (AD), the DNA-binding domain (DBD) and the tetramerization domain (TD) but differ in the C-terminus. Indeed, the p53 C-terminus contains a basic domain (BD) whereas p63/p73 have a sterile alpha motif (SAM) domain and an inhibitory domain (ID). In addition to the full-length proteins, the p53 family genes produce multiple isoforms truncated at the NH2- and/or C-terminus. Importantly, every functional domain is a determinant in the transactivation of specific target genes by the p53 family members. Distinct post-translational modifications and interactions with cofactors further modulate the transcriptional activity of the p53 family members in response to particular stress signals. Therefore, divergence in the composition of the p53 family proteins is responsible for the diversity of p53 family functions.