The current epidemic of obesity is driven, at least in part, by excessive caloric intake and fat intake has been implicated as a major contributing factor. The mammalian taste system displays marked plasticity, and it has been shown that the detection of fatty acids, the prototypical fat taste stimulus, leads to reduced sensitivity upon prolonged exposure to a high-fat diet. Increased obesity and metabolic disorders in postmenopausal females indicate that the female steroid hormone, estrogen, may contribute to metabolic homeostasis. Sex differences in the taste system were explored using a multidisciplinary approach to examine the ways in which estrogen influences the detection and recognition of fatty acids in the taste system. The findings suggest that estrogen in females is an essential factor in mediating sex differences in fat taste. Moreover, the stimulatory effect of fatty acid taste cell activation is further enhanced by estradiol (E2), suggesting a specific role of E2 in modulating peripheral fat detection. Genes and protein function important for the transduction pathway of fatty acids vary between males and females and these differences exist across the various taste papillae. In vivo support for the effect of estrogens in taste cells was provided by comparing the fatty acid responsiveness in males, intact females, and ovariectomized (OVX) female mice with and without hormone replacement. In general, females detected fatty acids at lower concentrations and the presence of circulating estrogens increased this apparent fat taste sensitivity. To study the long-term effects of fat intake in males and females, a diet-induced obesity model was used. Estrogen loss in females lead to increases in food intake, body weight, adiposity, and fat mass, and ultimately reduced taste cell activity. These metabolic effects were reversed by estrogen replacement in females. Taken together, these data indicate that increased circulating estrogens in the taste system may play a significant role in physiology and chemosensory cellular activation and, in turn, may alter taste driven behavior and overall nutrient intake.

ABSTRACT Assessment of the Effects of Malaria and Anemia in Pregnant Malawian Women Before and After Treatment of Moderate Malnutrition William Shipley Background: Moderate acute malnutrition (MAM) can lead to adverse maternal and infant outcomes and possibly further complications. Supplementary foods or treatments with high quality nutrients should be administered to those with MAM in hopes to increase the chance of healthy maternal and infant outcomes. Sometimes supplementary food is not enough to overcome MAM and disease may play a role, particularly in pregnant malnourished women. Objective: To determine if the effects of malaria and anemia moderated the effect of nutritional treatments (one of the three given nutritional interventions) used to improve malnutrition and achieve a MUAC ≥ 23 cm during study participation. Additionally, this research serves to assess whether the relationship between malaria and anemia is associated with malnutrition status. Methods: Women were given a dose of IPTp at each antenatal visit between zero and four total IPTp doses. Infant anthropometrics – length, weight, head circumference, and MUAC were taken at birth, 6 weeks, and 3 months. Maternal hemoglobin levels were assessed at enrollment and after 10 weeks of enrollment as well as infant hemoglobin at 3 months. Anemia was defined by a hemoglobin less than 11.0 g/dL. Mild anemia was defined as hemoglobin greater than 7.0 but less than 9.9 g/dL and moderate anemia was defined by hemoglobin values 9.9 or greater but less than 11.0 g/dL. Analysis was completed using ANOVA, and if any significant differences were observed, they were compared via Tukey HSD (continuous) or Chi-squared test (categorical). Results: Total number of IPTp doses was found to be a more statistically significant predictor of maternal weight gain during treatment than timing of the doses. It stands to reason that women receiving three or more IPTp doses was the most beneficial for women during treatment as it saw the highest increases in maternal weight gain. At baseline, women that achieved a MUAC > 23 cm during the study was 32.0% (n = 1805). The greatest proportion of women, after adjustment, that achieved a MUAC ≥ 23 cm was seen in women receiving four (47.3 %) and three (37.8 %) total IPTp doses during pregnancy. Maternal weight gain correlated closely with hemoglobin at enrollment (p-value = 0.0111). Total number of IPTp doses received during pregnancy was not found to have a statistical effect on infant hemoglobin or anemia at three months. Infant length at six weeks was higher in infants from mothers that received two or three IPTp doses compared to mothers that received one IPTp dose (p-value = 0.0218). A p-value below 0.05 by total number of IPTp doses was observed for infant weight, head circumference, and MUAC at birth, six weeks, and three months. Conclusion: At least three IPTp was effective in improving maternal weight gain and achievement of MUAC > 23 cm as well as improved many infant outcomes. Hemoglobin at enrollment was a predictor of maternal weight gain during tx but was not associated with any other outcomes.

Diabetes is the seventh leading cause of death in the United States, and nearly 34% of U.S. adults are prediabetic. CTRP3 is an adipose secreted protein that has shown to play a key role in glucose metabolism and insulin sensitivity, however, the research on CTRP3 total levels and its relationship to type 2 diabetes is controversial. The oligomeric state (protein structure) of CTRP3 in relation to metabolic dysfunction has not been studied. This study will be the first analysis of the circulating forms of CTRP3 in human blood. Hypothesis: The relative circulating amounts of the three oligomeric states of CTRP3 will differ in patients with type 2 diabetes. Methods: Human serum samples are analyzed using western blotting under native, reduced non-denaturing, and denaturing conditions. Results: In reducing non-denaturing conditions, three oligomeric states of CTRP3 were visualized in human serum: the high molecular weight (HMW) oligomer, the low molecular weight (LMW) oligomer, and the trimer. Conclusion: Reduced, non-denaturing conditions appear to yield the most effective separation of the three oligomeric states of CTRP3, and further studies aim to observe a difference in oligomeric state with a diabetic phenotype. Investigating the relationship of CTRP3’s oligomeric state with diabetic phenotype could present novel understanding of this protein’s possible protective effects against certain metabolic disorders.

<p>Current evidence suggests that both prediabetes and diabetes can reverse to normoglycemia; however, predictors of remission of these conditions are poorly understood. We performed analyses on 1,209 people with impaired fasting glucose and/or impaired glucose tolerance treated with placebo rosiglitazone and placebo ramipril in the DREAM trial. Normoglycemia was defined as a fasting plasma glucose <5.6 mmol/L and 2-hour plasma glucose <7.8 mmol/L on a 75 g oral glucose tolerance test (OGTT).</p> <p>The effects of baseline ALT and waist to hip ratio (WHR) on regression of prediabetes to normoglycemia 2 years later were found to be interdependent (p-value for interaction 0.01). Adjusted odds ratios ORs (95% CI) of regression to normoglycemia per 10 U/L increase in ALT were 0.79 (0.66-0.94) when WHR was at the mean minus 1 standard deviation (SD), 0.90 (0.80-1.02) when WHR was at the mean of 0.91, and 1.03 (0.90-1.18) when WHR was at the mean plus 1 SD. Adjusted ORs of regression to normoglycemia per 0.1 unit increase in WHR were 0.75 (0.60-0.95) when ALT was at the mean minus 1 SD, 0.91 (0.76-1.08) when ALT was at the mean of 25 U/L, and 1.09 (0.89-1.35) when ALT was at the mean plus 1 SD.</p> <p>Similarly, the effects of baseline ALT and WHR on AUC_{glucose0-120 min} obtained from the OGTT were found to be interdependent (p-value for interaction 0.056). A 10 U/L increase in ALT was associated with an adjusted AUC_{glucose0-120 min} increase of 19.5 (95% CI 5.3 to 33.7) min*mmol/L when WHR was at the mean minus 1 SD, 11.0 (1.4 to 20.6) min*mmol/L when WHR was at the mean of 0.91, and 2.5 (-9.2 to 14.1) min*mmol/L when WHR was at the mean plus 1 SD. A 0.1 unit increase in WHR was associated with an adjusted AUC_{glucose0-120 min} increase of 30.3 (10.2 to 50.3) min*mmol/L when ALT was at the mean minus 1 SD, 18.3 (3.8-32.9) min*mmol/L when ALT was at the mean of 25 U/L, and 6.4 (-11.5 to 24.3) min*mmol/L when ALT was at the mean plus 1 SD.</p> <p>In conclusion, high baseline ALT and WHR predict a lower likelihood of regression of prediabetes to normoglycemia and an increase in AUC_{glucose0-120 min} 2 years later; however, the effects of ALT and WHR on these outcomes are interdependent.</p> / Master of Science (MSc)

A dissertation submitted to the Faculty of medicine of the university of Witwatersrand, Johannesburg, in fulfilment of the requirements for the degree of Masters of science Johannesburg 1991 / Carnitine plays a role in the transport of activated long chain fatty acyl groups from the site of activation to the site of beta-oxidation in the mitochondria. Endogenous synthesis of carnitine from the amino acids methionine and lysine, takes place mainly in the liver. From there free and acyl carnitine are released into the blood and transported to other tissues.A few studies have indicated that poor nutritional status may lead to carnitine deficiency.[Abbreviated Abstract. Open document to view full version] / GR2017

Background: Diabetes is the sixth leading cause of death in the United States (U.S), and a major risk factor for cardiovascular disease (CVD). The prevalence of diabetes in central Appalachian region is higher than the rest of the nation (14.4% versus 9.0%, respectively). Objectives: Examine the association between multiple risk factors for CVD and diabetes in asymptomatic adults in central Appalachia. Methods: Between January 2012 and July 2016, 3,000 community-dwelling asymptomatic individuals from central Appalachia participated in screening for sub-clinical atherosclerosis. Participants were asked to report their diabetes status (yes/no). In addition, data on coronary artery calcium (CAC), a marker for sub-clinical coronary atherosclerosis, in quartiles (0, 1-99, 100-399, ≥400), obesity (body mass index ≥30 kg/m2), hypercholesterolemia (yes/no), hypertension (yes/no), current smoking (yes/no), sedentary lifestyle (yes/no), and family history of coronary artery disease (CAD) (yes/no), were collected. Multivariable logistic regression analyses were conducted to assess association between CVD risk factors and diabetes. Results: Of the 3,000 participants, 2,509 subjects (mean age: 58.3 years; SD = 9.8 years) had complete data on variables of interest. Approximately, 14% of the study population reported having type 2 diabetes. Among subjects with diabetes, 58% had a CAC score ≥1, 22% were obese, 17% had hypercholesterolemia, 20% had hypertension, 16% were current smokers, 17% had a sedentary lifestyle, and 15% had a family history of CAD. After adjusting for sex and age, having a CAC score of 1-99, 100-399, and ≥400 increased the odds of having diabetes (Odds ratio (OR): 1.4, 95% Confidence interval (CI) = 1.02-1.9; OR: 2.0, 95% CI = 1.4-2.8; OR: 3.1, 95% CI = 2.1-4.7, respectively) in a linear fashion. Being obese (OR: 3.2; 95% CI = 2.5-4.0), having hypercholesterolemia (OR: 1.8; 95% CI=1.4-2.4), being hypertensive (OR: 3.0; 95% CI= 2.3-3.8), being a smoker (OR: 1.5; 95% CI = 1.1-2.1), and being sedentary (OR: 1.6; 95% CI = 1.3-2.0) were significantly associated with diabetes. Having three (OR: 3.0; 95% CI=1.3-6.6), four (OR: 4.4; 95% CI=2.0-9.7), five (OR: 7.0; 95% CI=3.1-16.1) or six (OR: 9.9; 95% CI= 3.5-27.7) CVD risk factors significantly increased the odds of diabetes. Subjects with any of the seven risk factors under study were 1.7 times (95% CI= 1.5-1.9) more likely to have diabetes. Conclusion. Odds of type 2 diabetes increase with higher number of risk factors for CVD. Results support the use of multifaceted CVD and diabetes prevention programs to lower the incidence of type 2 diabetes.

Abstract available through Circulation.

Geography disparities exist in obesity and obesity related conditions. This study aimed to examine the geographic differences in obesity prevalence and its risk factors among Asian Americans in California. Data (n = 4,000) from the 2013–2014 California Health Interview Survey were used. Obesity (≥27.5 kg/m2) was defined according to the World Health Organization Asian body mass index cut points in Asian groups. Results suggest that 66.5% of Asians lived in urban areas. Among Asian adults, obesity prevalence was highest in Filipinos (33.8%) and lowest in Koreans (12.8%). Compared to rural Vietnamese, obesity prevalence was higher for urban Vietnamese (8.3% vs. 20.2%, p = 0.0318). Weighted multiple logistic regression analyses showed that being 45–64 years (vs. 65 years or above), being Japanese, Filipino, or other Asians (vs. Chinese) were associated with a higher odds of obesity among urban residents; whereas being 18–44 years and being 45–64 years (vs. 65 years or older), being male, having high school education (vs. having graduate education) were associated with a higher odds of obesity among rural residents. Being Vietnamese (vs. Chinese) was associated with 64% decreased odds of obesity only among rural residents (95% confidence interval = 0.14–0.94). The findings show geography disparities in obesity among Asians in California.

INTRODUCTION: Alcoholic cirrhosis occurs at a higher rate in female patients, at an earlier age, and with a lower consumption of alcohol compared to male patients. In our study on alcoholic fatty liver disease (AFLD) and adipokine levels, female mice showed a 50% higher mortality rate compared to ethanol fed male mice. The amount of ethanol consumed was similar between sexes when normalized to body weight. This resulted in our hypothesis that female mice are more susceptible to inflammation caused by alcohol consumption. METHODS: 12-week old female mice were fed a Lieber-Decarli alcohol diet (5% ETOH by volume) for 6-weeks and body weight and food intake were measured daily. Serum was collected from the mice and alanine aminotransferase (ALT), aspartate aminotransferase (AST), serum triglycerides, tumor necrosis factor alpha (TNF-α), and interleukin 6 (IL-6) levels were measured with the appropriate assays. RESULTS: In response to alcohol feeding, female mice showed significant increases in levels of ALT and AST compared to the male mice, indicating increased damage to the liver. TNF-α and IL-6 were also significantly increased in the ethanol fed female mice, indicating a significant increase in inflammation compared to the male ethanol fed mice. There was no difference found in the levels of serum triglycerides. CONCLUSION: These results indicate chronic alcohol consumption affects mice in a sex dependent manner, and that female mice are more susceptible to the adverse effects of alcohol than male mice. Increased female susceptibility to ethanol-induced damage must be considered in future ethanol-feeding studies.

INTRODUCTION: The liver is the primary organ responsible for the removal of toxic substances from the body by means of a variety of metabolic pathways. One class of proteins responsible for much of the body’s xenobiotic drug and alcohol metabolism is the Cytochrome P450 family of proteins. One protein, Cytochrome P450 Class E Subclass 2 (Cyp2E1), has an integral role in alcohol metabolism by the liver. Cyp2E1 becomes fully activated after an organism has consumed excessive amounts of alcohol excessive alcohol and works with aldehyde dehydrogenase (ALDH) to metabolize ethanol to acetaldehyde. Another metabolic protein, C1q TNF Related Protein 3 (CTRP3), has been shown to effectively prevent alcoholic fatty liver disease (AFLD), specifically with long-term alcohol-induced lipid accumulation. METHODS: In this experiment, 12-week old male mice were fed a Lieber-Decarli alcohol diet (5% ETOH by volume) for 6-weeks. The food intake and body weight of the mice was recorded each day. The mice in the experiment included both wild type and transgenic CTRP3 overexpressing mice. At the end of the 6-week period the mice were euthanized, and the liver was carefully removed, flash-frozen, and prepared for immunoblot analysis of the proteins. RESULTS: Cyp2E1 levels increased significantly in response to ethanol consumption. Cyp2E1 levels were further elevated in ethanol-fed CTRP3 transgenic overexpressing mice. Cyp2E1 levels in CTRP3 transgenic mice were nearly twice that of wild type ethanol-fed mice. CONCLUSIONS: The results of the experiment show a significant increase in Cyp2E1 in mice which overexpress CTRP3. This upregulation of Cyp2E1 with CTRP3 overexpression could explain the mechanism for reduced hepatic lipid accumulation in ethanol-fed CTRP3 transgenic mice.