High adherence to Western dietary pattern increases breast cancer risk (an EPIC-Spain study).

OBJECTIVE: To explore the association between three previously identified and validated dietary patterns (Western, Prudent and Mediterranean) and breast cancer risk by tumour subtype and menopausal status. METHODS: Data from the Spanish cohort of the European Prospective Investigation into Cancer and Nutrition study provided epidemiological information (including diet and cancer incidence) from 24,892 women (639 breast cancer cases) recruited between 1992 and 1996. The associations between adherence to the three dietary patterns and breast cancer risk (overall and by tumour subtype) were explored by fitting multivariate Cox proportional hazards regression models stratified by region, among other variables. A possible interaction with menopausal status (changing over time) was explored. RESULTS: No clear association of the Prudent and Mediterranean dietary patterns with breast cancer risk was found. When compared with women with a level of adherence to the Western diet in the first quartile, women with a level of adherence in the third (hazard ratio (95 % confidence interval) (HR(95%CI)):1.37 (1.07;1.77)) and fourth quartiles (1.37 (1.03;1.83)); p for curvature of splines = 0.016) showed a non-linear increased risk, especially postmenopausal women (HR (95 % CI) 1.30 (0.98;1.72) in the third and 1.42 (1.04;1.94) in the fourth quartiles; p for curvature of splines = 0.081) and for estrogen or progesterone receptor positive with human epidermal growth factor receptor 2 negative tumours (HR (95 % CI) 1.62 (1.10;2.38) and 1.71 (1.11;2.63) for the third and fourth quartiles respectively; p for curvature of splines = 0.013). CONCLUSIONS: Intake of foods such as high-fat dairy products, red and processed meats, refined grains, sweets, caloric drinks, convenience food and sauces might be associated with a higher risk of breast cancer.

Gender differences in the association between food costs and obesity in Korean adults: an analysis of a population-based cohort.

BACKGROUND/OBJECTIVES: Prior studies, mostly conducted in Western countries, have suggested that the low cost of energy-dense foods is associated with an increased risk of obesity. This study aimed to investigate the association between food costs and obesity risk among Koreans who may have different food cost and dietary patterns than those of Western populations. SUBJECTS/METHODS: We used baseline data from a cohort of 45,193 men and 83,172 women aged 40-79 years (in 2006-2013). Dietary intake information was collected using a validated food frequency questionnaire. Prudent and Western dietary patterns extracted via principal component analysis. Food cost was calculated based on Korean government data and market prices. Logistic regression analyses were performed to investigate the association of daily total, prudent, and Western food cost per calorie with obesity. RESULTS: Men in the highest total food cost quintile had 15% higher odds of obesity, after adjusting for demographic characteristics and lifestyle factors (adjusted odds ratio, 1.15; 95% confidence interval, 1.08-1.22; P-trend < 0.001); however, this association was not clear in women (P-trend = 0.765). While both men and women showed positive associations between prudent food cost and obesity (P-trends < 0.001), the association between Western food cost and obesity was only significant in men (P-trend < 0.001). CONCLUSIONS: In countries in which consumption of Western foods is associated with higher food costs, higher food costs are associated with an increased risk of obesity; however, this association differs between men and women.

Over-Expression of Intestinal Alkaline Phosphatase Attenuates Atherosclerosis.

[Figure: see text].

Association between Leisure Screen Time and Junk Food Intake in a Nationwide Representative Sample of Spanish Children (1-14 Years): A Cross-Sectional Study.

Evidence on the association between new patterns of leisure screen time and junk food consumption in Spanish children at the national level is scarce. The aim of this study is to assess the relation between daily leisure screen time and the frequency of sweet, soft drink, fast food, and snack intake in a representative sample of Spanish children and adolescents aged from 1 to 14 years. We conducted a cross-sectional study using a representative sample of the Spanish population under 15 years recruited for the 2017 Spanish National Health Survey (n = 5480). We dichotomized sweet, soft drink, fast food, and snack intake (high/low) and categorized daily leisure screen time (0-59, 60-119, 120-179, and ≥180 min). We calculated crude prevalence ratios and adjusted prevalence ratios, and their 95% confidence intervals (95% CI), of high frequency of sweet, soft drink, fast food, and snack intake. Children spending at least one hour of daily leisure screen time had higher prevalence of high frequency of sweet and snack intake than children being exposed less than one hour. For soft drinks and fast food, prevalence of high frequency intake was significantly higher from two and three hours of exposure, respectively. Longer periods of screen exposure in Spanish children during their leisure time may be associated with poorer dietary behaviors. The negative effects of excessive screen time in pediatrics population should be further studied.

The Long Noncoding RNA RP11-728F11.4 Promotes Atherosclerosis.

OBJECTIVE: Noncoding RNAs are emerging as important players in gene regulation and cardiovascular diseases. Their roles in the pathogenesis of atherosclerosis are not fully understood. The purpose of this study was to determine the role played by a previously uncharacterized long noncoding RNA, RP11-728F11.4, in the development of atherosclerosis and the mechanisms by which it acts. Approach and Results: Expression microarray analysis revealed that atherosclerotic plaques had increased expression of RP11-728F11.4 as well as the cognate gene FXYD6 (FXYD domain containing ion transport regulator 6), which encodes a modulator of Na+/K+-ATPase. In vitro experiments showed that RP11-728F11.4 interacted with the RNA-binding protein EWSR1 (Ewings sarcoma RNA binding protein-1) and upregulated FXYD6 expression. Lentivirus-induced overexpression of RP11-728F11.4 in cultured monocytes-derived macrophages resulted in higher Na+/K+-ATPase activity, intracellular cholesterol accumulation, and increased proinflammatory cytokine production. The effects of RP11-728F11.4 were enhanced by siRNA-mediated knockdown of EWSR1 and reduced by downregulation of FXYD domain containing ion transport regulator 6. In vivo experiments in apoE knockout mice fed a Western diet demonstrated that RP11-728F11.4 increased proinflammatory cytokine production and augmented atherosclerotic lesions. CONCLUSIONS: RP11-728F11.4 promotes atherosclerosis, with an influence on cholesterol homeostasis and proinflammatory molecule production, thus representing a potential therapeutic target. Graphic Abstract: A graphic abstract is available for this article.

Milk Consumption and Prostate Cancer: A Systematic Review.

Prostate cancer is the third most common cancer in men globally, and the most common cancer among men in the United States. Dietary choices may play an important role in developing prostate cancer; in particular, a higher dairy product intake has been associated with an increased risk of developing prostate cancer. The overall positive association between milk consumption and the risk of prostate cancer development and prostate cancer mortality has been well documented in multiple epidemiological studies. However, there is limited literature on the association between types of milk, as classified by fat content (skim, low fat, and whole), and the risk of developing prostate cancer. When further examining current state of the literature on this topic, there is a number of epidemiologic studies assessing the relationship between prostate cancer and milk consumption. On the contrary, very few experimental studies explore this topic. Further experimental research may be necessary to examine the relationship between dairy and dairy products consumption and the increased risk of development of prostate cancer. At this time, there are no formal clinical recommendations regarding dairy products consumption for patients who are at risk of prostate cancer development or who have a history of prostate cancer. In this manuscript, we sought to systematically review the existing literature on the association between milk consumption classified by fat content, and the risk of developing prostate cancer. These findings may be useful for the clinicians who provide recommendations for the patients at risk of developing prostate cancer.

NR4A1 Deletion in Marginal Zone B Cells Exacerbates Atherosclerosis in Mice-Brief Report.

OBJECTIVE: NR4A orphan receptors have been well studied in vascular and myeloid cells where they play important roles in the regulation of inflammation in atherosclerosis. NR4A1 (nerve growth factor IB) is among the most highly induced transcription factors in B cells following BCR (B-cell receptor) stimulation. Given that B cells substantially contribute to the development of atherosclerosis, we examined whether NR4A1 regulates B-cell function during atherogenesis. Approach and Results: We found that feeding Ldlr-/- mice a Western diet substantially increased Nr4a1 expression in marginal zone B (MZB) cells compared with follicular B cells. We then generated Ldlr-/- mice with complete B- or specific MZB-cell deletion of Nr4a1. Complete B-cell deletion of Nr4a1 led to increased atherosclerosis, which was accompanied by increased T follicular helper cell-germinal center axis response, as well as increased serum total cholesterol and triglycerides levels. Interestingly, specific MZB-cell deletion of Nr4a1 increased atherosclerosis in association with an increased T follicular helper-germinal center response but without any impact on serum cholesterol or triglyceride levels. Nr4a1-/- MZB cells showed decreased PDL1 (programmed death ligand-1) expression, which may have contributed to the enhanced T follicular helper response. CONCLUSIONS: Our findings reveal a previously unsuspected role for NR4A1 in the atheroprotective role of MZB cells.

Diet-Induced Obesity Promotes Kidney Endothelial Stiffening and Fibrosis Dependent on the Endothelial Mineralocorticoid Receptor.

Obesity is characterized by enhanced MR (mineralocorticoid receptor) activation, vascular stiffness, and associated cardiovascular and kidney disease. Consumption of a Western-style diet (WD), high in saturated fat and refined carbohydrates, by female mice, leads to obesity and vascular stiffening. Use of ECMR (endothelial cell-specific MR) knockout mice supports that ECMR activation is critical for development of vascular and cardiac fibrosis and stiffening. However, the role of ECMR activation in kidney inflammation and fibrosis remains unknown. We hypothesized that cell-specific deletion of ECMR would prevent WD-induced central aortic stiffness and protect the kidney from endothelial dysfunction and vascular stiffening. Four-week-old female ECMR KO and wild-type mice were fed either mouse chow or WD for 16 weeks. WD feeding increased body weight and fat mass, proteinuria, as well as vascular stiffness indices (pulse wave velocity and kidney artery stiffening) and impaired endothelial-dependent vasodilatation without blood pressure changes. The WD-induced kidney arterial stiffening was associated with attenuated eNOS (endothelial NO synthase) activation, increased oxidative stress, proinflammatory immune responses, alterations in extracellular matrix degradation pathways, and fibrosis. ECMR deletion prevented these abnormalities by improving eNOS activation and reducing macrophage proinflammatory M1 polarization, expression of TG2 (transglutaminase 2), and MMP (matrix metalloproteinase)-9. Our data support the concept that ECMR activation contributes to endothelial dysfunction, increased kidney artery fibrosis/stiffening, and impaired NOS (NO synthase) activation, processes associated with macrophage infiltration and polarization, inflammation, and oxidative stress, collectively resulting in tubulointerstitial fibrosis in females consuming a WD.

Low adherence to the western and high adherence to the mediterranean dietary patterns could prevent colorectal cancer.

PURPOSE: To assess if the associations found between three previously identified dietary patterns with breast, prostate and gastric cancer are also observed for colorectal cancer (CRC). METHODS: MCC-Spain is a multicase-control study that collected information of 1629 incident cases of CRC and 3509 population-based controls from 11 Spanish provinces. Western, Prudent and Mediterranean data-driven dietary patterns-derived in another Spanish case-control study-were reconstructed in MCC-Spain. Their association with CRC was assessed using mixed multivariable logistic regression models considering a possible interaction with sex. Risk by tumor site (proximal colon, distal colon, and rectum) was evaluated using multinomial regression models. RESULTS: While no effect of the Prudent pattern on CRC risk was observed, a high adherence to the Western dietary pattern was associated with increased CRC risk for both males [ORfourth(Q4) vs. first(Q1)quartile (95% CI): 1.45 (1.11;1.91)] and females [ORQ4 vs. Q1 (95% CI): 1.50 (1.07;2.09)] but seem to be confined to distal colon [ORfourth(Q4) vs. first(Q1)quartile (95% CI): 2.02 (1.44;2.84)] and rectal [ORQ4 vs. Q1 (95% CI): 1.46 (1.05;2.01)] tumors. The protective effect of the Mediterranean dietary pattern against CRC was observed for both sexes [males: ORQ4 vs. Q1 (95% CI): 0.71 (0.55;0.92); females: ORQ4 vs. Q1 (95% CI): 0.56 (0.40;0.77)] and for all cancer sites: proximal colon [ORQ4 vs. Q1 (95% CI): 0.70 (0.51;0.97)], distal colon [ORQ4 vs. Q1 (95% CI): 0.65 (0.48;0.89)], and rectum (ORQ4 vs. Q1 (95% CI): 0.60 (0.45;0.81)]. CONCLUSION: Our results are consistent with most of the associations previously found between these patterns and breast, prostate and gastric cancer risk and indicate that consuming whole fruits, vegetables, legumes, olive oil, nuts, and fish and avoiding red and processed meat, refined grains, sweets, caloric drinks, juices, convenience food, and sauces might reduce CRC risk.

Western diet induces endogen oxidative deoxyribonucleic acid damage and infl ammation in Wistar rats / Dieta ocidental induz endógeno dano oxidativo do ácido desoxirribonucleico e infl amação em ratos Wistar

ABSTRACT Objective Nutritional diseases such as metabolic syndrome, cardiovascular disorder, chronic inflammation or even cancer are observed in people who sustain their lifestyle by Western diet due to high calorie intake. The origin of these diseases are the degraded deoxyribonucleic acid structure. In this study, we investigated whether Western diet produced endogenous oxidative deoxyribonucleic acid damage, apoptosis or inflammation. Methods Twenty-eight male Wistar rats, aged 10-12 weeks, were divided into four groups. The rats in control group received the standard diet and the remaining rats were given one of the following three diets for four weeks: a high-fat diet containing 35% fat, a high-sucrose diet containing 69% sucrose and Western diet comprising both two types of diets. After treatment the serum 8-hydroxy-2-deoxyguanosine, poly (adenosine diphosphate ribose) polymerase-1, chitinase-3-like protein 1, soluble urokinase-type plasminogen activator receptor, Fas ligand and cytochrome c levels were measured. Results It was observed no changes in the serum soluble urokinase-type plasminogen activator receptor, Fas ligand and cytochrome c levels whereas a statistically significant increase in the serum 8-hydroxy-2-deoxyguanosine, poly (adenosine diphosphate ribose) polymerase-1 and chitinase-3-like protein 1 levels were found only in rats that were given Western diet. Conclusion The findings show that Western diet produced endogenous oxidative deoxyribonucleic acid damage, which then increased serum poly (adenosine diphosphate ribose) polymerase-1 levels, eventually leading to inflammation.

RESUMO Objetivo Doenças nutricionais, como síndrome metabólica, distúrbios cardiovasculares, inflamação crônica ou mesmo câncer, são observadas em pessoas que sustentam seu estilo de vida na dieta ocidental, caracterizada pela alta ingestão de calorias. Dado que a origem dessas doenças é a estrutura degradada do ácido desoxirribonucleico, o presente estudo investigou se a dieta ocidental produzia dano oxidativo endógeno ao ácido desoxirribonucleico, apoptose ou inflamação. Métodos Foram utilizados 28 ratos Wistar machos, com idade entre 10-12 semanas, divididos em quatro grupos. Os ratos do grupo controle receberam a dieta padrão, ao passo que os ratos restantes receberam uma das três dietas seguintes por quatro semanas: uma dieta rica em gordura contendo 35% de gordura; uma dieta rica em sacarose contendo 69% de sacarose; e dieta ocidental compreendendo os dois tipos de dietas. Após o tratamento soro 8-hidroxi-2-desoxiguanosina, poli (adenosina difosfato ribose) polimerase-1, quitinase-3-like proteína 1, uroquinase solúvel tipo de receptor ativador de plasminogênio, os níveis do ligante Fas e do citocromo c foram medidos. Resultados Não foram observadas alterações nos níveis séricos de uroquinase solúvel tipo de receptor ativador de plasminogênio, ligante Fas e citocromo c, enquanto um aumento estatisticamente significativo nos níveis séricos de 8-hidroxi-2-desoxiguanosina, poli (adenosina difosfato ribose) polimerase-1 e quitinase-3-like proteína 1 foi encontrado apenas em ratos que receberam dieta ocidental. Conclusão Os resultados mostram que a dieta ocidental produziu danos no ácido desoxirribonucleico oxidativo endógeno, o que aumentou os níveis séricos de poli (adenosina difosfato ribose) polimerase-1, levando à inflamação.

Adverse effect of early-life high-fat/high-carbohydrate ("Western") diet on bacterial community in the distal bowel of mice.

Obesity and other lifestyle diseases in modern society can be related to historical dietary changes from diets balanced in omega-6 and omega-3 to the unbalanced "Western-type" diet. It is recognized that diet influences the murine and human gut microbiome, and most research indicates that microbial diversity and composition are altered by high-fat diets (HFDs). However, good knowledge about the effects of early exposure to HFD on the maturation and structure of the bacterial community is limited. Using mice as model, we hypothesized that an HFD alters the early dynamic of the gut bacterial community toward an unstable/unhealthy state. By sequencing the V3 and V4 regions of the 16S ribosomal ribonucleic acid gene, we investigated the bacterial community in fecal samples of mice fed a control diet and an HFD at weaning (sampling time 1) and after 8 weeks of dietary intervention (11weeks of age; sampling time 2). Natural temporal microbiome maturation was evidenced by a general increase in microbial diversity and shifts in microbial community between sampling times 1 and 2 toward a mature community. However, the HFD led to significant structural segregation of the microbiome compared with controls; the HFD diet repressed health-enhancing bacteria (eg, Bifidobacterium and Akkermansia) and promoted health-detracting bacteria (ie, those associated with gut disorders, eg, Dorea). We suggest that early-life consumption of HFD negatively impacts the natural gut bacterial community maturation leading toward a potentially persistent unhealthy stage.

Endothelial Cell-Derived Von Willebrand Factor, But Not Platelet-Derived, Promotes Atherosclerosis in Apolipoprotein E-Deficient Mice.

OBJECTIVE: VWF (von Willebrand factor) is synthesized by endothelial cells and megakaryocytes and is known to contribute to atherosclerosis. In vitro studies suggest that platelet-derived VWF (Plt-VWF) is biochemically and functionally different from endothelial cell-derived VWF (EC-VWF). We determined the role of different pools of VWF in the pathophysiology of atherosclerosis. APPROACH AND RESULTS: Using bone marrow transplantation, we generated chimeric Plt-VWF, EC-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 in platelets and plasma on apolipoprotein E-deficient (Apoe-/-) background. Controls were chimeric Apoe-/- mice transplanted with bone marrow from Apoe-/- mice (wild type) and Vwf-/-Apoe-/- mice transplanted with bone marrow from Vwf-/-Apoe-/- mice (VWF-knock out). Susceptibility to atherosclerosis was evaluated in whole aortae and cross-sections of the aortic sinus in female mice fed a high-fat Western diet for 14 weeks. VWF-knock out, Plt-VWF, and Plt-VWF mice lacking a disintegrin and metalloprotease with thrombospondin type I repeats-13 exhibited reduced plaque size characterized by smaller necrotic cores, reduced neutrophil and monocytes/macrophages content, decreased MMP9 (matrix metalloproteinase), MMP2, and CX3CL1 (chemokine [C-X3-C motif] ligand 1)-positive area, and abundant interstitial collagen (P<0.05 versus wild-type or EC-VWF mice). Atherosclerotic lesion size and composition were comparable between wild-type or EC-VWF mice. Together these findings suggest that EC-VWF, but not Plt-VWF, promotes atherosclerosis exacerbation. Furthermore, intravital microscopy experiments revealed that EC-VWF, but not Plt-VWF, contributes to platelet and leukocyte adhesion under inflammatory conditions at the arterial shear rate. CONCLUSIONS: EC-VWF, but not Plt-VWF, contributes to VWF-dependent atherosclerosis by promoting platelet adhesion and vascular inflammation. Plt-VWF even in the absence of a disintegrin and metalloprotease with thrombospondin type I repeats-13, both in platelet and plasma, was not sufficient to promote atherosclerosis.

High adherence to the Western, Prudent, and Mediterranean dietary patterns and risk of gastric adenocarcinoma: MCC-Spain study.

BACKGROUND: The influence of dietary habits on the development of gastric adenocarcinoma is not clear. The objective of the present study was to explore the association of three previously identified dietary patterns with gastric adenocarcinoma by sex, age, cancer site, and morphology. METHODS: MCC-Spain is a multicase-control study that included 295 incident cases of gastric adenocarcinoma and 3040 controls. The association of the Western, Prudent, and Mediterranean dietary patterns-derived in another Spanish case-control study-with gastric adenocarcinoma was assessed using multivariable logistic regression models with random province-specific intercepts and considering a possible interaction with sex and age. Risk according to tumor site (cardia, non-cardia) and morphology (intestinal/diffuse) was evaluated using multinomial regression models. RESULTS: A high adherence to the Western pattern increased gastric adenocarcinoma risk [odds ratiofourth_vs._first_quartile (95% confidence interval), 2.09 (1.31; 3.33)] even at low levels [odds ratiosecond_vs._first_quartile (95% confidence interval), 1.63 (1.05; 2.52)]. High adherence to the Mediterranean dietary pattern could prevent gastric adenocarcinoma [odds ratiofourth_vs._first_quartile (95% confidence interval), 0.53 (0.34; 0.82)]. Although no significant heterogeneity of effects was observed, the harmful effect of the Western pattern was stronger among older participants and for non-cardia adenocarcinomas, whereas the protective effect of the Mediterranean pattern was only observed among younger participants and for non-cardia tumors. CONCLUSION: Decreasing the consumption of fatty and sugary products and of red and processed meat in favor of an increase in the intake of fruits, vegetables, legumes, olive oil, nuts, and fish might prevent gastric adenocarcinoma.

[The intestinal microbiome and metabolic diseases : From obesity to diabetes and nonalcoholic steatohepatitis]. / Intestinales Mikrobiom und metabolische Erkrankungen : Von der Adipositas zu Diabetes und nichtalkoholischer Steatohepatitis.

BACKGROUND: The intestinal microbiome consists of about 10 million genes, many of which encode digestive enzymes. This explains why animal and human experiments revealed that the intestinal microbiome adapts to food intake and optimizes energy harvest from food. This function is considered beneficial in states of lack of food, but following overnutrition, it might support the development of obesity. OBJECTIVES: The relevance of the intestinal microbiome for the pathogenesis of obesity and associated metabolic diseases such as fatty liver disease and type 2 diabetes mellitus and for the clinical management of such diseases shall be discussed. MATERIALS AND METHODS: Recent literature related to the topic has been selected, presented, and discussed with regard to the objectives. RESULTS: The intestinal microbiome plays a role in the pathogenesis of both obesity (by increasing the energy absorption from food) and fatty liver disease as well as type 2 diabetes mellitus (via induction of low-grade inflammation following translocation of lipopolysaccharides from the gut and dysregulation of metabolic pathways). CONCLUSIONS: The findings might have consequences for diagnosis (identification of risk groups) and therapy (usage of known and novel probiotics or bacterial metabolites) of metabolic diseases.

El perfil general del excedente nutrimental en México en el periodo 1990-2013: un enfoque a partir del suministro energético de macronutrimentos y grupos de alimentos / General profile of the nutrition surplus in Mexico from 1990-2013: An approach using the energy supplied by macronutrients and food groups

RESUMEN En este texto se analiza la evolución del suministro excesivo de kilocalorías en México desde 1990 a 2013. Para cada año del periodo se estimó el requerimiento de energía y macronutrimentos de la población mexicana y se lo contrastó con el respectivo suministro per cápita para estimar la discrepancia entre requerimiento y suministro. Las discrepancias se analizaron como serie temporal. Así, el excedente energético osciló entre 700 y 800 kcal/día per cápita en todo el periodo y los azúcares-dulcificantes aportaron el mayor suministro energético por encima de su requerimiento. El exceso de lípidos se incrementó de modo intenso y constante principalmente por el aumento de lípidos de carne de aves de corral y cerdo. El exceso aportado por las bebidas alcohólicas tendió a polarizarse en el creciente consumo de cerveza. En suma, a partir de los azúcares-dulcificantes y la carne se tendió a configurar el suministro energético y su respectivo excedente. Esto tiene implicaciones directas en la prevalencia de enfermedades crónicas no transmisibles así como en el uso insostenible de la tierra, el agua y la energía.

ABSTRACT This text analyzes the evolution of the excessive food energy supply in Mexico from 1990 to 2013. For each year, the energy and macronutrient requirements of the Mexican population were estimated and contrasted with the per capita energy supply. Discrepancies between requirement and supply were analyzed as a time series. The energy surplus ranged from 700 to 800 kcal per capita per day throughout the studied period and sugar/sweeteners contributed the highest above-requirement energy supply. Lipids excess increased steadily and intensely, mainly due to lipid increases from poultry and pork. Excess energy from alcoholic beverages tended to be concentrated into growing beer consumption. In summary, the energy supply and the corresponding surplus tended to be made up mainly of sugar/sweeteners and meat. This has direct implications for the prevalence of chronic non-communicable diseases as well as unsustainable use of land, water and energy.

High-fat Western diet-induced obesity contributes to increased tumor growth in mouse models of human colon cancer.

Strong epidemiologic evidence links colon cancer to obesity. The increasing worldwide incidence of colon cancer has been linked to the spread of the Western lifestyle, and in particular consumption of a high-fat Western diet. In this study, our objectives were to establish mouse models to examine the effects of high-fat Western diet-induced obesity on the growth of human colon cancer tumor xenografts, and to examine potential mechanisms driving obesity-linked human colon cancer tumor growth. We hypothesize that mice rendered insulin resistant due to consumption of a high-fat Western diet will show increased and accelerated tumor growth. Homozygous Rag1tm1Mom mice were fed either a low-fat Western diet or a high-fat Western diet (HFWD), then human colon cancer xenografts were implanted subcutaneously or orthotopically. Tumors were analyzed to detect changes in receptor tyrosine kinase-mediated signaling and expression of inflammatory-associated genes in epididymal white adipose tissue. In both models, mice fed an HFWD weighed more and had increased intra-abdominal fat, and tumor weight was greater compared with in the low-fat Western diet-fed mice. They also displayed significantly higher levels of leptin; however, there was a negative correlation between leptin levels and tumor size. In the orthotopic model, tumors and adipose tissue from the HFWD group displayed significant increases in both c-Jun N-terminal kinase activation and monocyte chemoattractant protein 1 expression, respectively. In conclusion, this study suggests that human colon cancer growth is accelerated in animals that are obese and insulin resistant due to the consumption of an HFWD.

Endothelial Mineralocorticoid Receptor Deletion Prevents Diet-Induced Cardiac Diastolic Dysfunction in Females.

Overnutrition and insulin resistance are especially prominent risk factors for the development of cardiac diastolic dysfunction in females. We recently reported that consumption of a Western diet (WD) containing excess fat (46%), sucrose (17.5%), and high fructose corn syrup (17.5%) for 16 weeks resulted in cardiac diastolic dysfunction and aortic stiffening in young female mice and that these abnormalities were prevented by mineralocorticoid receptor blockade. Herein, we extend those studies by testing whether WD-induced diastolic dysfunction and factors contributing to diastolic impairment, such as cardiac fibrosis, hypertrophy, inflammation, and impaired insulin signaling, are modulated by excess endothelial cell mineralocorticoid receptor signaling. Four-week-old female endothelial cell mineralocorticoid receptor knockout and wild-type mice were fed mouse chow or WD for 4 months. WD feeding resulted in prolonged relaxation time, impaired diastolic septal wall motion, and increased left ventricular filling pressure indicative of diastolic dysfunction. This occurred in concert with myocardial interstitial fibrosis and cardiomyocyte hypertrophy that were associated with enhanced profibrotic (transforming growth factor ß1/Smad) and progrowth (S6 kinase-1) signaling, as well as myocardial oxidative stress and a proinflammatory immune response. WD also induced cardiomyocyte stiffening, assessed ex vivo using atomic force microscopy. Conversely, endothelial cell mineralocorticoid receptor deficiency prevented WD-induced diastolic dysfunction, profibrotic, and progrowth signaling, in conjunction with reductions in macrophage proinflammatory polarization and improvements in insulin metabolic signaling. Therefore, our findings indicate that increased endothelial cell mineralocorticoid receptor signaling associated with consumption of a WD plays a key role in the activation of cardiac profibrotic, inflammatory, and growth pathways that lead to diastolic dysfunction in female mice.

Who Uses the Internet as a Source of Nutrition and Dietary Information? An Australian Population Perspective.

BACKGROUND: The Internet contains a plethora of nutrition information. Health organizations are increasingly using the Internet to deliver population-wide health information and interventions. Effective interventions identify their target population and their needs; however, little is known about use of the Internet as a source of nutrition information. OBJECTIVE: The aim was to assess the change in prevalence and demographic characteristics of Western Australian adults accessing the Internet as a source of nutrition information and identify specific information needs. METHODS: Data were pooled from the Western Australian Department of Health's 3-yearly Nutrition Monitoring Survey Series telephone survey between 1995 and 2012 of 7044 participants aged 18 to 64 years. Outcome variables were the main sources of nutrition information used in the last year and yes/no responses to 4 suggestions to what would make it easier to eat a healthy diet. Sociodemographic variables were collected. RESULTS: The proportion of respondents using the Internet for nutrition information increased from <1% in 1995-2001 to 9.1% in 2004 and 33.7% in 2012. Compared to 2004, logistic regression showed that the odds of using the Internet for this information increased significantly in 2009 (OR 2.84, 95% CI 2.07-3.88) and 2012 (OR 5.20, 95% CI 3.86-7.02, P<.001). Respondents using the Internet as a source were more likely to be female (OR 1.30, 95% CI 1.05-1.60, P=.02), live in a metropolitan area (OR 1.26, 95% CI 1.03-1.54, P=.03), born in countries other than Australia/UK/Ireland (OR 1.41, 95% CI 1.07-1.85, P=.02), more educated (university: OR 2.46, 95% CI 1.77-3.42, P<.001), and were less likely to be older (55-64 years: OR 0.38, 95% CI 0.25-0.57, P<.001). The majority of respondents agreed the following information would assist them to make healthier choices: more ways to prepare healthy foods (72.0%, 95% CI 70.7-73.3), quicker ways to prepare healthy foods (79.0%, 95% CI 77.8-80.1), how to choose healthy foods (68.8%, 95% CI 67.5-70.1), and knowing more about cooking (54.7%, 95% CI 53.3-56.1). Those using the Internet for nutrition information were more likely than nonusers to want to know quicker ways to prepare healthy foods (83.0% vs 78.1%, P=.005) and information on choosing healthy foods (76.3% vs 67.3%, P<.001). CONCLUSIONS: Use of the Internet as a main source of nutrition information has grown rapidly since 2004; one-third of Western Australian adults reported using the Internet for this purpose in 2012. Information on preparing healthy foods (ideas, quicker ways), choosing ingredients, and knowing more about cooking would make it easier to eat a healthy diet. For Internet users, emphasis should be on quicker ways and choosing ingredients. These finding have implications for policy makers and practitioners and suggest that traditional health promotion tactics should continue to be used to reach the broader population.