Obesity is an urgent global public health concern as prevalence rates continue to increase, especially among children. At the cellular level obesity is defined by an increase in adipocyte number (hyperplasia) and size (hypertrophy). Both lead to the dysfunction of adipose tissue, which has been identified as the link between obesity and chronic disease. Bioactive compounds, naturally occurring in fruits and vegetables, hold enormous potential in regulating adipocyte biology. Quercetin, the most commonly consumed dietary flavonoid, is a strong potential anti-obesity agent that has been implicated as an AMP-activated protein kinase (AMPK) activator and shown to ameliorate symptoms of metabolic syndrome in vivo. Here we investigated quercetin’s effect on (1) adipogenesis, the process of increasing adipocyte number, and (2) metabolism of mature adipocytes. In 3T3-L1 preadipocytes, quercetin dose-dependently inhibited adipogenesis, as evidenced by decreased lipid accumulation and expression of adipogenic markers such as peroxisome proliferator-activated receptor (PPAR) γ, CCAAT/ enhancer binding protein (C/EBP) α, adipocyte fatty acid binding protein 2 (aP2), and acetyl-CoA carboxylase (ACC) on mRNA and protein levels. This inhibitory effect was limited to the early stages of adipogenesis (0-36 hours), and quercetin treatment altered the normal expression pattern of cell cycle related genes Cyclin A and p27, indicating quercetin may inhibit adipogenesis through cell cycle events. We next investigated quercetin’s ability to activate AMPK and the metabolic pathways related to AMPK activation: lipolysis and b-oxidation. Quercetin increased phosphorylation of AMPK and its downstream target ACC. Further, quercetin treatment (100μM) increased free fatty acid content in the media through an AMPK-dependent mechanism. Quercetin up-regulated mRNA expression of uncoupling proteins 3 (UCP3) and peroxisome proliferator-activated receptor-gamma co-activator 1 alpha (PGC-1a), indicating that quercetin may induce mitochondrial oxidative pathways, also through an AMPK-dependent pathway. These findings suggest (1) quercetin inhibits adipogenesis through the regulation of early cell cycle events required for adipogenic differentiation, and (2) quercetin’s activation of AMPK induces lipolytic and oxidative pathways. Taken together, quercetin could be further developed as an anti-obesity agent because of its potential to inhibit both hyperplasia and hypertrophy in vitro.

Introduction: Gestational Diabetes Mellitus (GDM) results in complications affecting both mother and child. The implementation of metabolomics to assess metabolite alterations is needed to better understand its etiology. Prior research by our lab in first trimester samples of GDM patients indicated altered fatty acid utilization and purine degradation products. Objective: Metabolomics analysis was conducted on third trimester (28 -35 weeks) plasma samples to observe differences associated with GDM. Methods: Fifty samples taken from the Healthy Beginnings trial and their corresponding data were included in the study. Plasma samples were analyzed using UPLC-MS with metabolomic assays for primary metabolomics, aminomics, and lipidomics. Plasma metabolite comparisons were made between participants who developed GDM (n=27) and individuals without GDM (n=23) through UPLC-MS analysis with metabolomic assays for primary metabolomics, aminomics, and lipidomics. Dietary intake was collected via 24 hour recalls to assess dietary differences between groups. Results: Fatty acid oxidation-related metabolites altered included lower decanoyl-, dodecenoyl-, and lauroyl-carnitine (p Conclusion: In support of previous research in first trimester samples, metabolomics revealed altered markers of fatty acid metabolism and purine degradation in GDM patients. Further research is necessary to validate these findings and identify the key roles these metabolites may play in GDM development. Keywords: Gestational diabetes mellitus, metabolomics, acylcarnitines, purines

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.

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.

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.