scholarly journals Dietary phosphatidylcholine promotes breast cancer in the hyperlipidemic E0771 murine model

2020 ◽  
Author(s):  
Fredrick O Onono ◽  
Lakshman Chelvarajan ◽  
Baoxiang Yan ◽  
Ebubechi Adindu ◽  
Esias Bedingar
Keyword(s):  
Breast Cancer ◽  
Mass Spectrometry ◽  
Amino Acids ◽  
Tumor Growth ◽  
Cancer Development ◽  
Primary Breast Tumor ◽  
High Fat ◽  
Breast Cancer Development ◽  
High Fat Diets ◽  
Fat Diets

Abstract BackgroundCancer cells are characterized by aberrant phosphatidylcholine (PC) metabolism. PC can be synthesized de novo or absorbed from diet, after digestion, by the intestinal enterocytes. Here, we investigated the association of dietary intake of PC and breast cancer development in mice. MethodsWe used tandem mass spectrometry methods to quantitate PC content of various fat sources used to manufacture rodent diets. Rodent diets were then formulated with either casein or amino acids in place of casein. To test the effects of dietary PC on tumor growth we fed low density lipoprotein receptor-null (LDLR–/–) mice high fat diets formulated with casein (high PC) or amino acids in place of casein (low PC). Endogenous PC biosynthesis and levels of total circulated plasma PC was monitored using stable isotope tracer choline and mass spectrometry analysis. Tumors were induced in mice after 12 weeks of high fat diet feeding. Since PC-derived molecules are important transducers of mitogenic signals, we tested the effects of inhibiting production of lysophosphatidic acid (LPA) using a recently described autotaxin (ATX) inhibitor. Finally, plasma inflammatory cytokine levels were analyzed to determine the effects of diets and ATX inhibition on systemic cytokine milieu. ResultsWe found that casein is the main source of PC when present in rodent diets. Replacing casein with amino acids increased the relative proportion of endogenously biosynthesized PC in mouse plasma. Compared to diets containing casein, amino acid-defined diets decreased primary tumor growth in the hyperlipidemic estrogen-receptor positive E0771 breast cancer mouse model. Inhibition of autotaxin with the potent inhibitor PAT-505 did not attenuate breast cancer development in these hyperlipidemic mice. Further, replacing casein with amino acids or treatment with PAT-505 significantly reduced systemic markers of inflammation. ConclusionOur results show that casein is a significant source of PC when present in rodent diets. Diets formulated with amino acids in place of casein have higher proportion of circulating PC from the endogenous biosynthetic pool. Casein-containing high fat diets promote primary breast tumor development in mice through mechanisms that involve systemic inflammation but is independent of LPA production by autotaxin.

scholarly journals Nicotine Synergizes with High-Fat Diet to Induce an Anti-Inflammatory Microenvironment to Promote Breast Tumor Growth

2020 ◽  
Vol 2020 ◽  
pp. 1-17
Author(s):  
Thalia Jimenez ◽  
Theodore Friedman ◽  
Jaydutt Vadgama ◽  
Vineeta Singh ◽  
Alexandria Tucker ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Cells ◽  
Breast Tumor ◽  
High Fat Diet ◽  
Breast Cancer Cells ◽  
Cancer Development ◽  
High Fat ◽  
Breast Cancer Development ◽  
Anti Inflammatory

Breast cancer results from a complex interplay of genetics and environment that alters immune and inflammatory systems to promote tumorigenesis. Obesity and cigarette smoking are well-known risk factors associated breast cancer development. Nicotine known to decrease inflammatory signals also modulates immune responses that favor breast cancer development. However, the mechanisms by which nicotine and obesity contribute to breast cancer remain poorly understood. In this study, we examined potential mechanisms by which nicotine (NIC) and high-fat diet (HFD) promote growth of HCC70 and HCC1806 xenografts from African American (AA) triple negative (TN) breast cancer cells. Immunodeficient mice fed on HFD and treated with NIC generated larger HCC70 and HCC1806 tumors when compared to NIC or HFD alone. Increased xenograft growth in the presence of NIC and HFD was accompanied by higher levels of tissue-resident macrophage markers and anti-inflammatory cytokines including IL4, IL13, and IL10. We further validated the involvement of these players by in vitro and ex vivo experiments. We found a proinflammatory milieu with increased expression of IL6 and IL12 in xenografts with HFD. In addition, nicotine or nicotine plus HFD increased a subset of mammary cancer stem cells (MCSCs) and key adipose browning markers CD137 and TMEM26. Interestingly, there was upregulation of stress-induced pp38 MAPK and pERK1/2 in xenografts exposed to HFD alone or nicotine plus HFD. Scratch-wound assay showed marked reduction in proliferation/migration of nicotine and palmitate-treated breast cancer cells with mecamylamine (MEC), a nicotine acetylcholine receptor (nAchR) antagonist. Furthermore, xenograft development in immune-deficient mice, fed HFD plus nicotine, was reduced upon cotreatment with MEC and SB 203580, a pp38MAPK inhibitor. Our study demonstrates the presence of nicotine and HFD in facilitating an anti-inflammatory tumor microenvironment that influences breast tumor growth. This study also shows potential efficacy of combination therapy in obese breast cancer patients who smoke.

scholarly journals The Combination of Mulberry Extracts and Silk Amino Acids Alleviated High Fat Diet-Induced Nonalcoholic Hepatic Steatosis by Improving Hepatic Insulin Signaling and Normalizing Gut Microbiome Dysbiosis in Rats

2019 ◽  
Vol 2019 ◽  
pp. 1-17 ◽  
Author(s):  
Sunmin Park ◽  
Ting Zhang ◽  
Jing Yi Qiu ◽  
Xuangao Wu
Keyword(s):  
Oxidative Stress ◽  
Amino Acids ◽  
Disease Control ◽  
Normal Control ◽  
Insulin Signaling ◽  
High Fat ◽  
Hepatic Insulin Signaling ◽  
High Fat Diets ◽  
Fat Diets ◽  
Better Than

Mulberry water extracts (MB) and silk amino acids (SA) are reported to improve oxidative stress and inflammation, respectively. We hypothesized whether the mixture of mulberry water extracts and silk amino acids can alleviate nonalcoholic fatty liver disease (NAFLD) induced by high fat diets. Male Sprague Dawley rats were orally provided with high fat diets containing different ratios of MB and SA (1:3, MS1:3, or 1:5, MS1:5) or cellulose (the disease-control) for 12 weeks. Rats had 200 or 600 mg/kg bw of MS1:3 and MS1:5 (MS1:3-L, MS1:3-H; MS1:5-L, and MS1:5-H). Rats in the normal-control group were fed the 20% fat diet with cellulose. Disease-control rats exhibited much greater triglyceride (TG) deposition in the liver than the normal-control rats along with increased body weight gain, visceral fat mass, serum concentrations of cholesterol, triglyceride and nonesterified fatty acid (NEFA), and insulin resistance. Disease-control rats also had liver damage with increased oxidative stress and inflammation compared to the normal-control rats. MS1:3-H and MS1:5-H were found to have greater hepatic glycogen accumulation and decreased hepatic TG, insulin resistance, and dyslipidemia, with MS1:5-H being similar to the normal-control. MS1:3-H alleviated oxidative stress with lower hepatic lipid peroxide compared to MS1:5-H whereas MS1:5-H ameliorated inflammation and hepatocyte damage better than MS1:3-H. Both MS1:3-H and MS1:5-H potentiated hepatic insulin signaling (pAkt⟶pACC) and reduced the mRNA expression of TG synthesis genes mRNA (FAS and SREBP-1c). In the gut microbiome MS1:3-H elevated the ratio of Bacteroidales to Clostridiales in the cecum better than MS1:5-H but MS1:5-H reduced the proinflammatory Turicibacterales. In conclusion, both MS1:3-H and MS1:5-H prevented liver damage induced by high fat diets, mainly by suppressing oxidative stress and inflammation, respectively. MS1:3 and MS1:5 might be used as therapeutic agent for NAFLD.

High-Fat Diets and Breast Cancer Risk

JAMA ◽  
1992 ◽  
Vol 268 (15) ◽  
pp. 2080 ◽  
Author(s):  
Geoffrey R. Howe
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
High Fat ◽  
High Fat Diets ◽  
Fat Diets

scholarly journals Paternal programming of breast cancer risk in daughters in a rat model: opposing effects of animal- and plant-based high-fat diets

2016 ◽  
Vol 18 (1) ◽  
Author(s):  
Camile Castilho Fontelles ◽  
Luiza Nicolosi Guido ◽  
Mariana Papaléo Rosim ◽  
Fábia de Oliveira Andrade ◽  
Lu Jin ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Breast Cancer Risk ◽  
Cancer Risk ◽  
Rat Model ◽  
High Fat ◽  
High Fat Diets ◽  
Opposing Effects ◽  
Fat Diets ◽  
Paternal Programming

Na+,HCO3–-cotransporter NBCn1 (Slc4a7) accelerates ErbB2-induced breast cancer development and tumor growth in mice

Oncogene ◽  
2018 ◽  
Vol 37 (41) ◽  
pp. 5569-5584 ◽  
Author(s):  
Soojung Lee ◽  
Trine V. Axelsen ◽  
Nicolai Jessen ◽  
Stine F. Pedersen ◽  
Pernille Vahl ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Tumor Growth ◽  
Cancer Development ◽  
Breast Cancer Development

Non-Fasting Factor VII Coagulant Activity (FVII:C) Increased by High-Fat Diet

1994 ◽  
Vol 71 (06) ◽  
pp. 755-758 ◽  
Author(s):  
E M Bladbjerg ◽  
P Marckmann ◽  
B Sandström ◽  
J Jespersen
Keyword(s):  
High Fat Diet ◽  
Fat Content ◽  
Factor Vii ◽  
Amidolytic Activity ◽  
High Fat ◽  
Low Fat Diet ◽  
Increased Risk ◽  
Coagulant Activity ◽  
High Fat Diets ◽  
Fat Diets

SummaryPreliminary observations have suggested that non-fasting factor VII coagulant activity (FVII:C) may be related to the dietary fat content. To confirm this, we performed a randomised cross-over study. Seventeen young volunteers were served 2 controlled isoenergetic diets differing in fat content (20% or 50% of energy). The 2 diets were served on 2 consecutive days. Blood samples were collected at 8.00 h, 16.30 h and 19.30 h, and analysed for triglycerides, FVII coagulant activity using human (FVII:C) or bovine thromboplastin (FVII:Bt), and FVII amidolytic activity (FVIPAm). The ratio FVII:Bt/FVII:Am (a measure of FVII activation) increased from fasting levels on both diets, but most markedly on the high-fat diet. In contrast, FVII: Am (a measure of FVII protein) tended to decrease from fasting levels on both diets. FVII:C rose from fasting levels on the high-fat diet, but not on the low-fat diet. The findings suggest that high-fat diets increase non-fasting FVII:C, and consequently may be associated with increased risk of thrombosis.

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