Non-alcoholic fatty liver disease (NAFLD) represents the major cause of pediatric chronic liver pathology in the United States. The objective of this study was to investigate the effect of partial substitution of dietary lard by an isocaloric amount of olive or coconut oil on endpoints of NAFLD. Thirty-eight 15-d-old Iberian pigs housed in pens balanced for weight and sex were randomly assigned to receive 1 of 3 hypercaloric high-fructose high-fat (HFF) diets for 10 weeks: 1) lard (LAR; n=5 pens), 2) lard + olive oil (OLI, n=10), and 3) lard + coconut oil (COC; n=10). Additional pigs (BSL, n=4) were fed a eucaloric diet to establish baseline values. Animals were euthanized at 85 d of age after blood sampling. Liver tissue was collected for histology, metabolomics, and transcriptomics. Compared with BSL, OLI decreased high-density lipoproteins, phosphatidylcholines (PC), and total cholesterol in blood, and increased acylcarnitines in liver, whereas COC increased triacylglycerides (TAGs) in liver and blood. All HFF diets increased bile acids in liver, and decreased choline and fibroblast growth factor 19 in liver and blood. OLI and COC increased hepatic steatosis, necrosis, ballooning, and composite lesion score compared with LAR. OLI decreased gene expression of carnitine O-palmitoyltransferase 1, and COC increased expression of fatty acid binding proteins and acyl-CoA synthetase. In conclusion, partial replacement of dietary lard with olive and coconut oil dysregulated acylcarnitine metabolism and lipogenesis in the liver, increasing the severity of NAFLD in juvenile pigs.

Type 2 diabetes mellitus (T2DM) is a chronic condition recognized as the inability to maintain glucose homeostasis, typically presenting with insulin resistance and systemic inflammation. With the prevalence of T2DM and major risk factors such as prediabetes and obesity increasing each year, there is a crucial need to identify strategies for the management and prevention of this condition. Addressing lifestyle-related risk factors through consumption of a well-balanced, nutritious diet and maintaining regular moderate- to high-intensity physical activity may provide a strategy for improving glycemic control, improving metrics of body composition, and decreasing the inflammatory response associated with metabolic dysregulation. Twenty-two overweight to obese adults with a medical diagnosis of T2DM, indicators of prediabetes, or who were metabolically healthy participated in Cal Poly’s Nutrition and Exercise in Type 2 Diabetes (CPNET) study. The study protocol included adherence to a Mediterranean-style diet, daily consumption of a high-quality whey protein supplement, and adherence to the Physical Activity Guidelines for Americans for 16 weeks. Body composition data, via dual-energy X-ray absorptiometry (DXA), and fasting blood samples were collected at baseline and following the intervention. Due to restrictions associated with the global COVID-19 pandemic, only 13 participants were able to return for the second data collection following the 16-week intervention. The prediabetic and T2DM groups exhibited reductions in fasting plasma glucose to that of normal and prediabetic levels, respectively, while the T2DM group also showed improvement in hemoglobin A1c to the prediabetic level. Additionally, the metabolically healthy, overweight group demonstrated significant improvements in adiposity, while the obese prediabetic and T2DM groups showed non-significant improvements in all measured metrics of body composition. No changes were observed in inflammatory biomarkers. Thus, our results suggest that adherence to a well-balanced nutritious diet and regular physical activity may improve parameters of glycemic control and provide benefits to body composition that help manage and prevent the development of T2DM.

Yes / The DNA Damage Response (DDR) pathways sense DNA damage and coordinate robust DNA repair and bypass mechanisms. A series of repair proteins are recruited depending on the type of breaks and lesions to ensure overall survival. An increase in glucose levels was shown to induce genome instability, yet the links between DDR and glucose are still not well investigated. In this study, we aimed to identify dysregulation in the transcriptome of normal and cancerous breast cell lines upon changing glucose levels. We first performed bioinformatics analysis using a microarray dataset containing the triple-negative breast cancer (TNBC) MDA-MB-231 and the normal human mammary epithelium MCF10A cell lines grown in high glucose (HG) or in the presence of the glycolysis inhibitor 2-deoxyglucose (2DG). Interestingly, multiple DDR genes were significantly upregulated in both cell lines grown in HG. In the wet lab, we remarkably found that HG results in severe DNA damage to TNBC cells as observed using the comet assay. In addition, several DDR genes were confirmed to be upregulated using qPCR analysis in the same cell line. Our results propose a strong need for DDR pathways in the presence of HG to oppose the severe DNA damage induced in cells. / Wellcome Trust

College students undergo stressors (e.g., potential financial strain, changes in workload or location), which may precipitate metabolic syndrome (MetS) risk associated with obesity and high blood pressure. Concerning rises in young adult obesity and type 2 diabetes, prompt study into MetS risk factor prevalence and awareness in youthful populations transitioning to new environments, such as college. This study assessed perceived stress, coping resources, and disease awareness differences in the first time on campus and final-year students associated with MetS risk factors (elevated body mass index (BMI) and blood pressure). We hypothesized lower stress perception, lower weight gain and blood pressure, higher MetS knowledge, and more positive coping strategies in final-year students. We conducted a longitudinal cohort study of 43 undergraduates with a baseline assessment in September (T0) and a follow-up in December (T1). BMI and blood pressure were measured at each visit and compared to baseline predictors of MetS knowledge, perceived stress, and coping resources. Though trends in MetS knowledge, perceived stress, and coping scores followed those in our hypothesis, only differences in weight and BMI change were statistically significant. The mixed-effects regression analysis did not find any statistically significant trends. First-time on-campus students gained an average of 1.736 kg, and their average BMI increased by 0.485 kg/m2. Conversely, final year students lost 0.313 kg, and their average BMI decreased by 0.210 kg/m2. Information on blood pressure was inconclusive. The average increase in weight/BMI in first-time on-campus students compared to final-year students highlights the need to provide education and resources to protect against metabolic syndrome risk in young adults. Trends in final year student clinical outcomes and their predictors illustrate how education may be a protective factor against MetS risk.

Epidemic obesity in the U.S. has prompted exploration of causal factors related to the built environment. Recent research has noted statistical associations between the spatial accessibility of retail food sources, such as supermarkets, convenience stores, and restaurants, and individual characteristics such as weight, socioeconomic status, and race/ethnicity. These studies typically use residential proximity or neighborhood density to food sources as the measure of accessibility. Assessing food environments in this manner, however, is very limiting. Since most people travel outside of their neighborhood on a daily basis, the retail food sources available to individuals residing in the same area could vary widely. This research developed new techniques for describing food accessibility or food environments based upon individuals’ activity and travel patterns, or their activity spaces. Researchers have previously used travel diaries to study activity and travel behavior, but these are burdensome for participants, and are prone to recall error and other inaccuracies. This study explored use of global positioning system (GPS) to identify participants' activity spaces, and employed a geographic information system (GIS) to assess the retail food sources located within these spaces. This produced ‘activity-based’ measures of individual retail food accessibility that do not rely on areal units, nor require travel diaries. Participants included 121 residents of a census tract in Lexington, Kentucky who agreed to carry GPS trackers for three workdays, and complete surveys regarding weight, socioeconomic and demographic characteristics, and diet and food purchasing habits. The types and relative frequencies of food locations within their activity spaces were compared to those within close proximity to the census tract. Dietary and food purchasing habits were subsequently analyzed in relation to activity-based food environment measures. The results of this study demonstrate substantial potential for misclassification bias in food accessibility research based on residential proximity or neighborhood density. Furthermore, this study observed statistically significant relationships between the new activity-based food accessibility measures and some personal characteristics and food-related behaviors. Despite some limitations, the techniques developed in this research show great potential for future research, which should be explored further in a variety of contexts.

O presente trabalho teve por objetivo avaliar a microbiota subgingival pela técnica de Checkerboard e o perfil de citocinas por imunoensaio com princípio sanduíche baseado na tecnologia fluxometria do fluido gengival e soro em indivíduos não obesos; e em indivíduos com obesidade, antes e após cirurgia bariátrica. Diferenças na microbiota bucal foram observadas entre não obesos e obesos para 19 espécies bacterianas, particularmente E. corrodens que apresentou diferenças significativas em obesos, com consequente redução após a perda de peso. As citocinas IL-1b, IL-6, IL-10, IL-13, IL-17, TNF-a, leptina e adiponectina apresentaram diferenças estatisticamente significantes (p<0,05) quando esses indivíduos foram comparados. Todas as citocinas analisadas no soro diminuíram após a redução de peso, apenas a adiponectina apresentou concentrações significativamente mais elevadas (p<0,05). Assim, a obesidade promove alterações na microbiota subgengival e na resposta imunológica local e sua prevenção ou controle pode favorecer a saúde bucal. / In this study, the aimed to evaluate the subgingival microbiota using Checkerboard technique and the cytokines profile by using immunoassay based on the flowmetry gingival fluid and serum in non-obese and obese individuals, before and after bariatric surgery. Differences were observed in the oral microbiota between nonobese and obese for 19 bacterial species, particularly E. corrodens that showed significant differences in obese, with a consequent reduction after weight loss. The cytokines IL-1b, IL-6, IL-10, IL-13, IL-17, TNF-a, leptin and adiponectin were statistically different (p <0.05) when these individuals were compared. All analyzed cytokines in serum decreased after weight reduction only adiponectin concentrations showed significantly higher (p <0.05). Thus, obesity causes changes in the subgingival microbiota and the local immune response, and prevention and control can promote oral health.

Submitted by (lucia.rodrigues@ufrpe.br) on 2017-02-10T13:39:50Z No. of bitstreams: 1 Rodolfo Jose Cavalcanti Souto.pdf: 1672049 bytes, checksum: 9d25ef84b343968c6b40907e7241f724 (MD5) / Made available in DSpace on 2017-02-10T13:39:50Z (GMT). No. of bitstreams: 1 Rodolfo Jose Cavalcanti Souto.pdf: 1672049 bytes, checksum: 9d25ef84b343968c6b40907e7241f724 (MD5) Previous issue date: 2013-02-25 / Pregnancy disease (PD) occurs mainly in sheep and goats, supplemented with concentrate, whose expression is due to negative energy balance during the transition period in which the females present in the clinical hyperketonemia, hypoglycemia, ketonuria, anorexia and signs neurological can progress to death. This paper aims to conduct a study of the biochemical and hormonal profile in sheep and goats, and pathology of the liver parenchyma and renal function in sheep with PD diagnosis. We used data (case report forms) and biological materials (serum, plasma and tissue) of 45 sheep and 22 goats that were answered in Bovine Clinic, Campus Garanhuns / UFRPE, diagnosed with PD, from January 2007 to October 2012 . The blood analyzes were: urea, creatinine, albumin, total protein, globulin, β-hydroxybutyrate, non-esterified fatty acids (NEFA), glucose, fructosamine, amylase, aspartate aminotransferase (AST), gamma glutamyl transferase (GGT), vitamin B12 , folic acid, cortisol, insulin, and total ionized Ca, P, Ca: P ratio, Mg, Na, K. Cl. Besides the characterization of macro and histopathological findings of the liver and kidneys of sheep that died. Urine was examined in the presence of ketones employing the reagent strip commercial. Sheep subjected to necropsy were collected fragments of liver and kidneys for histopathological analysis. Marked clinical abnormalities were observed in goats with high values for urea, creatinine, NEFA, β-hydroxybutyrate, amylase and cortisol, while total protein, albumin, total calcium, ionized calcium, phosphorus, the calcium and phosphorus, sodium and insulin were found below the reference values for the species. As for glucose, 77.28% of goats were normoglycemic TP and / or hyperglycemic, while only 22.72% were hypoglycemic. The results of the sheep revealed elevated levels of urea, creatinine, glucose, fructosamine, NEFA's, β-hydroxybutyrate, cortisol, chlorine, AST, GGT amylase and folic acid as the variable insulin, total calcium, ionized calcium and potassium were values below the reference values for the species. As for glucose, 82.90% of the sheep were normoglycemic with PD and / or hyperglycemic, while only 17.10% were hypoglycemic. With regard to the macroscopic group of sheep with lower body score showed an increase of the liver, and yellowing and the cutting surface, while the sheep with higher body score these findings were more intense. Kidney was observed on the surface in some pallor of lean animals and light yellowish in animal fat. Regarding histological alterations, it was found in animals with lower body condition, liver vacuolated ranging from rare discreet. As the renal injury, rare tubular vacuolation of epithelial cells were observed in 28,57%. In sheep with higher body condition scores greater percentage of vacuolation in the liver was observed and ranged from moderate to severe. Regarding renal lesions, 33.33% of the animals showed severe lesion vacuolization of tubular epithelial cells. Marked clinical and metabolic changes were observed in goats and sheep PD, in which the increase of the energy profile certain metabolites and hormones are important diagnostic tools for assessing the magnitude of negative energy balance and the clinical condition of the animals. In sheep PD causes significant changes in renal parenchyma, characterized by vacuolization of cells that are associated tubular body condition score of the animal. / A toxemia da prenhez (TP) ocorre principalmente em ovelhas e cabras, suplementadas com concentrado, cuja manifestação se deve a um balanço energético negativo durante o período de transição, no qual as fêmeas apresentam quadro clínico de hipercetonemia, hipoglicemia, cetonúria, anorexia e sinais neurológicos que pode evoluir para a morte. Este trabalho se propõe a realizar um estudo do perfil bioquímico e hormonal em cabras e ovelhas, e anatomopatológico do parênquima hepático e renal em ovelhas com diagnóstico de TP. Foram utilizados dados (fichas clínicas) e material biológico (soro, plasma e tecido) de 45 ovelhas e 22 cabras que foram atendidas na Clínica de Bovinos, Campus Garanhuns/UFRPE, diagnosticadas com TP, no período de janeiro de 2007 a outubro de 2012. As análises realizadas no sangue foram: uréia, creatinina, albumina, proteína total, globulina, β-hidroxibutirato, ácidos graxos não esterificados (AGNE), glicose, frutosamina, amilase, aspartato aminotransferase (AST), gama glutamiltransferase (GGT), vitamina B12, ácido fólico, cortisol, insulina, Ca total e ionizável, P, relação Ca:P, Mg, Na, K. Cl. Além da caracterização dos achados macro e histopatológicos do fígado e rins das ovelhas que vieram a óbito. Na urina foi examinada a presença de corpos cetônicos empregando-se a fita reagente comercial. Das ovelhas submetidas à necropsia foram coletados fragmentos de fígado e rins para análise histopatológica. Marcadas alterações clínicas foram observadas nas cabras, com valores elevados para ureia, creatinina, AGNE, β-hidroxibutirato, amilase e cortisol, enquanto que a proteína total, albumina, cálcio total, cálcio ionizado, fósforo, a relação cálcio e fósforo, o sódio e a insulina encontraram-se abaixo dos valores de referência para a espécie. Quanto à glicemia, 77,28% das cabras com TP eram normoglicêmicas e/ou hiperglicêmicas, enquanto apenas 22,72% eram hipoglicêmicas. Os resultados obtidos das ovelhas revelaram valores elevados de ureia, creatinina, glicose, frutosamina, AGNE’s, β-hidroxibutirato, cortisol, cloro, AST, GGT amilase e ácido fólico enquanto que a variável insulina, cálcio total, cálcio ionizado e potássio estavam com valores abaixo dos valores de referência para a espécie. Quanto à glicemia, 82,90% das ovelhas com TP eram normoglicêmicas e/ou hiperglicêmicas, enquanto apenas 17,10% eram hipoglicêmicas. Quanto aos achados macroscópicos no grupo de ovelhas com menor escore corporal, foi observado aumento do fígado, além de coloração amarelada na superfície e ao corte, enquanto que nas ovelhas com maior escore corporal estes achados foram mais intensos. Nos rins foi observada palidez na superfície em alguns dos animais magros e leve coloração amarelada em animais gordos. Quanto às alterações histológicas, verificou-se, nos animais com menor escore corporal, fígado com vacuolização que variou de rara a discreta. Quanto às lesões renais, raras vacuolizações em células epiteliais tubulares foram observadas em 28,57%. Nas ovelhas com maior escore corporal maior percentual de vacuolização no fígado foi observada e variou de moderada a acentuada. Quanto às lesões renais, 33,33% dos animais apresentaram lesão acentuada de vacuolizações em células epiteliais tubulares. Marcadas alterações clínicas e metabólicas foram observadas em cabras e ovelhas com TP, em que o aumento de certos metabólitos do perfil energético e hormonal tornam-se importantes ferramentas de diagnóstico para avaliar o balanço energético negativo e a magnitude da condição clínica dos animais. Em ovelhas a TP provoca alterações significativas no parênquima renal, caracterizadas por vacuolização de células tubulares e que estão associados ao escore corporal dos animais.

Abstract available through http://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.1037.5.

Abstract available through http://www.fasebj.org/doi/abs/10.1096/fasebj.31.1_supplement.1037.5.

Aim: To examine the association of cardiovascular disease risk factors with and their cumulative effect on coronary artery calcium in hard-to-reach asymptomatic patients with diabetes. Methods: : A total of 2563 community-dwelling asymptomatic subjects from Central Appalachia participated in coronary artery calcium screening at a heart centre. Binary variable was used to indicate that coronary artery calcium was either present or absent. Independent variables consisted of demographic and modifiable risk factors and medical conditions. Descriptive statistics and multinomial logistic regression analyses were conducted. Results: : In total, 55.8% and 13.7% of study participants had subclinical atherosclerosis (coronary artery calcium ⩾1) and diabetes, respectively. The presence of coronary artery calcium was higher in subjects with diabetes (68.5%) than those without (53.8%). Compared to subjects without diabetes with coronary artery calcium = 0, obesity, hypertension, hypercholesterolaemia and smoking increased the odds of the presence of coronary artery calcium (coronary artery calcium score ⩾1) regardless of diabetes status; however, with larger odds ratios in subjects with diabetes. Compared to subjects without diabetes with coronary artery calcium score = 0, having 3, 4 and ⩾5 risk factors increased the odds of presence of coronary artery calcium in subjects with diabetes by 14.06 (confidence interval = 3.26–62.69), 32.30 (confidence interval = 7.41–140.82) and 47.12 (confidence interval = 10.35–214.66) times, respectively. Conclusion: : There is a need for awareness about subclinical atherosclerosis in patients with diabetes and more research about coronary artery calcium in subpopulations of patients.