The role of self-efficacy in a low fat high fiber intervention to reduce breast cancer risk among African American women

Purpose. To determine if self-efficacy (SE) changes predicted total fat (TF) and total fiber (TFB) intake and the relationship between SE changes and the two dietary outcomes. ^ Design. This is a secondary analysis, utilizing baseline and first follow up (FFU) data from the NULIFE, a randomized trial. ^ Setting. Nutrition classes were taught in the Texas Medical Center in Houston, Texas. ^ Participants. 79 pre-menopausal, 25--45 year old African American women with an 85% response rate at FFU. ^ Method. Dietary intake was assessed with the Arizona Food Frequency Questionnaire and SE with the Self Efficacy for Dietary Change Questionnaire. Analysis was done using Stata version 9. Linear and logistic regression was used with adjustment for confounders. ^ Results. Linear regression analyses showed that SE changes for eating fruits and vegetables predicted total fiber intake in the control group for both the univariate (P = 0.001) and multivariate (P = 0.01) models while SE for eating fruits and vegetables at first follow-up predicted total fiber intake in the intervention for both models (P = 0.000). Logistic regression analyses of low fat SE changes and 30% or less for total fat intake, showed an adjusted OR of 0.22 (95% CI = 0.03, 1.48; P = 0.12) in the intervention group. The logistic regression analyses of SE changes in fruits and vegetables and 10g or more for total fiber intake, showed an adjusted OR of 6.25 (95% CI = 0.53, 72.78; P = 0.14) in the control group. ^ Conclusion. SE for eating fruits and vegetables at first follow-up predicted intervention groups' TFB intake and intervention women that increased their SE for eating a low fat diet were more likely to achieve the study goal of 30% or less calories from TF. SE changes for eating fruits and vegetables predicted the control's TFB intake and control women that increased their SE for eating fruits and vegetables were more likely to achieve the study goal of 10 g or more from TFB. Limitations are use of self-report measures, small sample size, and possible control group contamination.^

Western diet, but not high fat diet, causes derangements of fatty acid metabolism and contractile dysfunction in the heart of Wistar rats.

Obesity and diabetes are associated with increased fatty acid availability in excess of muscle fatty acid oxidation capacity. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in the development of skeletal-muscle insulin resistance. We tested the hypothesis that 'Western' and high fat diets differentially cause maladaptation of cardiac- and skeletal-muscle fatty acid oxidation, resulting in cardiac contractile dysfunction. Wistar rats were fed on low fat, 'Western' or high fat (10, 45 or 60% calories from fat respectively) diet for acute (1 day to 1 week), short (4-8 weeks), intermediate (16-24 weeks) or long (32-48 weeks) term. Oleate oxidation in heart muscle ex vivo increased with high fat diet at all time points investigated. In contrast, cardiac oleate oxidation increased with Western diet in the acute, short and intermediate term, but not in the long term. Consistent with fatty acid oxidation maladaptation, cardiac power decreased with long-term Western diet only. In contrast, soleus muscle oleate oxidation (ex vivo) increased only in the acute and short term with either Western or high fat feeding. Fatty acid-responsive genes, including PDHK4 (pyruvate dehydrogenase kinase 4) and CTE1 (cytosolic thioesterase 1), increased in heart and soleus muscle to a greater extent with feeding a high fat diet compared with a Western diet. In conclusion, we implicate inadequate induction of a cassette of fatty acid-responsive genes, and impaired activation of fatty acid oxidation, in the development of cardiac dysfunction with Western diet.

Western diet changes cardiac acyl-CoA composition in obese rats: a potential role for hepatic lipogenesis.

The "lipotoxic footprint" of cardiac maladaptation in diet-induced obesity is poorly defined. We investigated how manipulation of dietary lipid and carbohydrate influenced potential lipotoxic species in the failing heart. In Wistar rats, contractile dysfunction develops at 48 weeks on a high-fat/high-carbohydrate "Western" diet, but not on low-fat/high-carbohydrate or high-fat diets. Cardiac content of the lipotoxic candidates--diacylglycerol, ceramide, lipid peroxide, and long-chain acyl-CoA species--was measured at different time points by high-performance liquid chromatography and biochemical assays, as was lipogenic capacity in the heart and liver by qRT-PCR and radiometric assays. Changes in membranes fluidity were also monitored using fluorescence polarization. We report that Western feeding induced a 40% decrease in myocardial palmitoleoyl-CoA content and a similar decrease in the unsaturated-to-saturated fatty acid ratio. These changes were associated with impaired cardiac mitochondrial membrane fluidity. At the same time, hepatic lipogenic capacity was increased in animals fed Western diet (+270% fatty acid elongase activity compared with high-fat diet), while fatty acid desaturase activity decreased over time. Our findings suggest that dysregulation of lipogenesis is a significant component of heart failure in diet-induced obesity.

Impact of a modified dietary plan on the health related quality of life of minority participants in the Women's Healthy Eating and Living (WHEL) Study

Advances in medical technology, in genetics, and in clinical research have led to early detection of cancer, precise diagnosis, and effective treatment modalities. Decline in cancer incidence and mortality due to cancer has led to increased number of long-term survivors. However, the ethnic minority population has not experienced this decline and still continues to carry a disparate proportion of the cancer burden. Majority of the clinical research including survivorship studies have recruited and continue to recruit a convenient sample of middle- to upper-class Caucasian survivors. Thus, minorities are underrepresented in cancer research in terms of both clinical studies and in health related quality of life (HRQOL) studies. ^ Life style and diet have been associated with increased risk of breast cancer. High vegetable low fat diet has been shown to reduce recurrence of breast cancer and early death. The Women's Healthy Eating and Living Study is an ongoing multi-site randomized controlled trial that is evaluating the high-vegetable low fat diet in reducing the recurrence of breast cancer and early death. The purpose of this dissertation was to (1) compare the impact of the modified diet on the HRQOL during the first 12-month period on specific Minorities and matched Caucasians; (2) identify predictors that significantly impact the HRQOL of the study participants; and (3) using the structural equation modeling assess the impact of nutrition on the HRQOL of the intervention group participants. Findings suggest that there are no significant differences in change in HRQOL between Minorities and Caucasians; between Minorities in the intervention group and those in the comparison group; and between women in the intervention group and those in the comparison group. Minority indicator variable and Intervention/Comparison group indicator variable were not found to be good predictors of HRQOL. Although the structural equation models suggested viable representation of the relationship between the antecedent variables, the mediating variables and the two outcome variables, the impact of nutrition was not statistically significant to be included in the model. This dissertation, by analyzing the HRQOL of minorities in the WHEL Study, attempted to add to the knowledge base specific to minority cancer survivors. ^

Adaptation and maladaptation of heart and skeletal muscle to different diets in a rodent model of human obesity

Obesity and diabetes are metabolic disorders associated with fatty acid availability in excess of the tissues' capacity for fatty acid oxidation. This mismatch is implicated in the pathogenesis of cardiac contractile dysfunction and also in skeletal muscle insulin resistance. My dissertation will present work to test the overall hypothesis that "western" and high fat diets differentially affect cardiac and skeletal muscle fatty acid oxidation, the expression of fatty acid responsive genes, and cardiac contractile function. Wistar rats were fed a low fat, "western," or high fat (10%, 45%, or 60% calories from fat, respectively) diet for acute (1 day to 1 week), short (4 to 8 weeks), intermediate (16 to 24 weeks), or long (32 to 48 weeks) term. With high fat diet, cardiac oleate oxidation increased at all time points investigated. In contrast, with western diet cardiac oleate oxidation increased in the acute, short and intermediate term, but not in the long term. Consistent with a maladaptation of fatty acid oxidation, cardiac power (measured ex vivo) decreased with long term western diet only. In contrast to the heart, soleus muscle oleate oxidation increased only in the acute and short term with either western or high fat feeding. Transcript analysis revealed that several fatty acid responsive genes, including pyruvate dehydrogenase kinase 4, uncoupling protein 3, mitochondrial thioesterase 1, and cytosolic thioesterase 1 increased in heart and soleus muscle to a greater extent with high fat diet, versus western diet, feeding. In conclusion, the data implicate inadequate induction of a cassette of fatty acid responsive genes in both the heart and skeletal muscle by western diet resulting in impaired activation of fatty acid oxidation, and the development of cardiac dysfunction. ^

Evaluation of the effectiveness of the Fresh and Healthy Program

Background. Diets high in fat and calories are promoted by the toxic food environment in which high fat, high calorie foods are readily accessible, thus contributing to high rates of overweight and obesity.^ Hypothesis. Changing the food environment to make low-fat, low-calorie foods readily identifiable and accessible while simultaneously offering incentives for choosing those foods will result in increased consumption of targeted foods, thus decreasing caloric and fat intake and ultimately decreasing obesity rates.^ Objective. To conduct an outcome evaluation study on the effectiveness of The Fresh & Healthy Program, a health promotion project designed to promote healthy eating among The Methodist Hospital employees by labeling and promoting low calorie, low fat items in the hospital cafeteria. ^ Program. By promoting healthy eating, this program seeks to address unhealthy dietary behaviors, one of the most widely known and influential behavioral causes of obesity. Food items that are included in the program meet nutritional criteria for calories and fat and are labeled with a special logo. Program participants receive incentives for purchasing Fresh & Healthy items. The program was designed and implemented by a team of registered dietitians, two health education specialists, and retail foodservice managers at The Methodist Hospital in the Texas Medical Center in Houston and has been in existence since April 2006.^ Methods. The evaluation uses a non-randomized, one-group, time series design to evaluate the effect of the program on sales of targeted food items.^ Key words. point-of-purchase, menu labeling, environmental obesity interventions, food pricing interventions ^

Body fat distribution and serum lipids in children and adolescents

Previous studies of normal children have linked body fat but not body fat distribution (BFD), to higher blood pressures, lipids, and insulin resistance (Berenson et al., 1988) BFD is a well-established risk factor for cardiovascular disease in adults (Björntorp, 1988). This study investigates the relation of BFD and serum lipids at baseline in children from Project HeartBeat!, a study of the growth and development of cardiovascular risk factors in 678 children in three cohorts measured initially at ages 8, 11, and 14 years. Initially, two of four indices of BFD were significantly related to the lipids: ratio of upper to lower body skinfolds (ln US:LS) and conicity (C Index). A factor analysis reduced the information in the serum lipids to two vectors: (1) total cholesterol + LDL-cholesterol and (2) HDL-cholesterol − triglycerides, which together accounted for 85% of the lipid variation. Using each serum lipid and vector as separate dependent variables, linear and quadratic regression models were constructed to examine the predictive ability of the two BFD variables, controlling for total body fat, gender, ethnicity (Black, non-Black) and maturation. Linear models provided an acceptable fit. Percent body fat (%BF) was a significant predictor in each and every lipid model, independent of age, maturation, or ethnicity (p ≤ 0.05). No BFD variable entered the equation for total or LDL-cholesterol, although there was a significant maturity by BFD interaction for LDL (ln US:LS was a significant predictor in more mature individuals). Both %BF and BFD (by way of Conicity) were significant predictors of HDL-cholesterol and triglycerides (p ≤ 0.01). All models were statistically significant at a high level (p ≤ 0.01), but adjusted R 2's for all models were low (0.05–0.15). Body fat distribution is a significant predictor of lipids in normal children, but secondarily to %BF, and for LDL-cholesterol in particular, the relation is dependent on maturity status. ^

Physiologic and psychosocial stage-based differences for dietary fat consumption in women with type 2 diabetes

Purpose. This cross-sectional, observational study explored differences among groups staged for intent to decrease dietary fat intake in women with type 2 diabetes in relation to demographic, weight concern, physiological, and psychosocial variables. ^ Methods. A sample of 100 community-dwelling, English-speaking women, who were over age 30 and had type 2 diabetes for at least a year, was accessed through a culturally diverse endocrinology clinic. Subjects completed 7 self-report instruments: demographic sheet, with 11-point weight satisfaction scale; staging algorithm; fat intake (MEDFICTS); depression (CES-D); diabetes-specific dietary knowledge (ADKnowl), social support and self-efficacy scales (SE-Type 2). Physiological variables were abstracted from the medical record (HbA 1c, blood pressure, serum cholesterol and triglycerides). ^ Results. The women's average age was 57.69 years ( SD = 3.07); 50% were married. Subjects were well-educated ( M = 14 years; SD = 3.33), with average diabetes duration of 10.57 years (SD = 9.11), high body mass index (M = 35.72; SD = 8.36), low diabetes-specific dietary knowledge, low weight satisfaction, but in good diabetes control. Racial/ethnic composition was 44% non-Hispanic-White-American, 18% Hispanic-White-American, 15% non-Hispanic-African-American, 16% Hispanic-African-American and 5% other. Fat intake was low and differed by racial/ethnic demographics. The highest fat intake scores were for non-Hispanic-African-Americans (M = 53), followed by Hispanic-White-Americans (M = 51), non-Hispanic-White-Americans (M = 45), and Hispanic-African-Americans (M = 32), who had the lowest fat intake scores. ^ MANOVA analyses revealed no significant differences between stages of behavior change in relation to psychosocial or weight concern variables, age, education, HbA1c, or cholesterol levels. Single women were more likely to be in the three preaction stages (precontemplation, contemplation, and preparation); married women were equally distributed across stages (the preaction stages plus action and maintenance). African-American women (Hispanic and non-Hispanic) were more likely in contemplation and preparation. Triglycerides were higher in women in the action stage than contemplation or preparation. Systolic blood pressure was higher in action than preparation; diastolic blood pressure was higher in action than preaction. ^ Conclusions. Healthcare professionals should consider race, ethnicity, and marital status in client interactions. Dietary intake can vary according to both race and ethnicity; collapsing racial/ethnic groups can alter means and distributions, generating faulty conclusions. Further research is warranted to explore relationships between dietary self-care and marital status, race, ethnicity, and physiological variables. ^

The low molecular weight (LMW) isoforms of cyclin E provide a novel mechanism of cell cycle deregulation

Cyclin E, in complex with cyclin dependent kinase 2 (CDK2), is a positive regulator of G1 to S phase progression of the cell cycle. Deregulation of G1/S phase transition occurs in the majority of tumors. Cyclin E is overexpressed and post-translationally generates low molecular weight (LMW) isoforms in breast cancer, but not normal cells. Such alteration of cyclin E is linked to poor prognosis. Therefore, we hypothesized that the LMW isoforms of cyclin E provide a novel mechanism of cell cycle de-regulation in cancer cells. Insect cell expression system was used to explore the biochemical properties of the cyclin E isoforms. Non-tumorigenic (76NE6) and tumorigenic (T47D) mammary epithelial cells transfected with the cyclin E isoforms and breast tumor tissue endogenously expressing the LMW isoforms were used to study the biologic consequences of the LMW isoforms of cyclin E. All model systems studied show that the LMW forms (compared to full-length cyclin E) have increased kinase activity when partnered with CDK2. Increases in the percentage of cells in S phase and colony formation were also observed after overexpression of LMW compared to full-length cyclin E. The LMW isoforms of cyclin E utilize several mechanisms to attain their hyper-activity. They bind CDK2 more efficiently, and are resistant to inhibition by cyclin dependent kinase inhibitors (CKIs) as compared to full-length cyclin E. In addition, the LMW isoforms sequester the CKIs from full-length cyclin E abrogating the overall negative regulation of cyclin E. Despite their correlation with adverse biological consequences, the direct role of the LMW isoforms of cyclin E in mediating tumorigenesis remained unanswered. Subsequent to LMW cyclin E expression in 76NE6 cells, they lose their ability to enter quiescence and exhibit genomic instability, both characteristic of a tumor cell phenotype. Furthermore, injection of 76NE6 cells overexpressing each of the cyclin E isoforms into the mammary fat pad of nude mice revealed that the LMW isoforms of cyclin E yield tumors, whereas the full-length cyclin E does not. In conclusion, the LMW isoforms of cyclin E utilize several mechanisms to acquire a hyperactive phenotype that results in deregulation of the cell cycle and initiates the tumorigenic process in otherwise non-transformed mammary epithelial cells. ^

Growth and development of body fat distribution from skinfold measurements: Longitudinal principal components

Longitudinal principal components analyses on a combination of four subcutaneous skinfolds (biceps, triceps, subscapular and suprailiac) were performed using data from the London Longitudinal Growth Study. The main objectives were to discover at what age during growth sex differences in body fat distribution occur and to see if there is continuity in body fatness and body fat distribution from childhood into the adult status (18 years). The analyses were done for four age sectors (3mon-3yrs, 3yrs-8yrs, 8yrs-18yrs and 3yrs-18yrs). Longitudinal principal component one (LPC1) for each age interval in both sexes represents the population mean fat curve. Component two (LPC2) is a velocity of fatness component. Component three (LPC3) in the 3mon-3yrs age sector represents infant fat wave in both sexes. In the next two age sectors component three in males represents peaks and shifts in fat growth (change in velocity), while in females it represents body fat distribution. Component four (LPC4) in the same two age sectors is a reversal in the sexes of the patterns seen for component three, i.e., in males it is body fat distribution and in females velocity shifts. Components five and above represent more complicated patterns of change (multiple increases and decreases across the age interval). In both sexes there is strong tracking in fatness from middle childhood to adolescence. In males only there is also a low to moderate tracking of infant fat with middle to late childhood fat. These data are strongly supported in the literature. Several factors are known to predict adult fatness among the most important being previous levels of fatness (at earlier ages) and the age at rebound. In addition we found that the velocity of fat change in middle childhood was highly predictive of later fatness (r $\approx -$0.7), even more so than age at rebound (r $\approx -$0.5). In contrast to fatness (LPC1), body fat distribution (LPC3-LPC4) did not track well even though significant components of body fat distribution occur at each age. Tracking of body fat distribution was higher in females than males. Sex differences in body fat distribution are non existent. Some sex differences are evident with the peripheral-to-central ratios after age 14 years. ^

Acceleration of the PanIN Development in Mice Expressing Oncogenic K-Ras Due to a High Fat Diet

Obesity is postulated to be one of the major risk factors for pancreatic cancer, and recently it was indicated that an elevated body mass index (BMI correlates strongly with a decrease in patient survival. Despite the evident relationship, the molecular mechanisms involved are unclear. Oncogenic mutation of K-Ras is found early and is universal in pancreatic cancer. Extensive evidence indicates oncogenic K-Ras is not entirely active and it requires a triggering event to surpass the activity of Ras beyond the threshold necessary for a Ras-inflammation feed-forward loop. We hypothesize that high fat intake induces a persistent low level inflammatory response triggering increased K-Ras activity and that Cox-2 is essential for this inflammatory reaction. To determine this, LSL-K-Ras mice were crossed with Ela-CreER (Acinar-specific) or Pdx-1-Cre (Pancreas-specific) to “knock-in” oncogenic K-Ras. Additionally, these animals were crossed with Cox-2 conditional knockout mice to access the importance of Cox-2 in the inflammatory loop present. The mice were fed isocaloric diets containing 60% energy or 10% energy from fat. We found that a high fat diet increased K-Ras activity, PanIN formation, and fibrotic stroma significantly compared to a control diet. Genetic deletion of Cox-2 prevented high fat diet induced fibrosis and PanIN formation in oncogenic K-Ras expressing mice. Additionally, long term consumption of high fat diet, increased the progression of PanIN lesions leading to invasive cancer and decreased overall survival rate. These findings indicate that a high fat diet can stimulate the activation of oncogenic K-Ras and initiate an inflammatory feed forward loop requiring Cox-2 leading to inflammation, fibrosis, and PanINs. This mechanism could explain the relationship between a high fat diet and elevated risk for pancreatic cancer.