bluuebunny/crossref_metadata_2025_split huggingface dataset:
Effect of stimulation to the oral cavity on diet‐induced thermogenesis and the substrate oxidation of macronutrients
Authors: Hamada Yuka , Hayashi Naoyuki 
Published: November 2023

We recently showed that diet‐induced thermogenesis (DIT) was greater after slowly eating a test meal than when eating it rapidly (Hamada et al. 2014), but it was unclear whether this was due to the duration of eating or to mastication stimulation to the oral cavity. Changes in the substrate oxidation of macronutrients inducing DIT are also unclear. The present study examined the effect of stimulation to the oral cavity on DIT and the substrate oxidation of macronutrients. Eleven healthy normal‐weight males (mean±SD: age, 23±1 years; height, 176±4 cm; body mass, 68±5 kg; BMI, 22±1 kg/m2) participated in three trials with a randomized crossover design. A 200‐mL cocoa‐flavored drink (200 kcal) was divided into ten 20‐mL cups. After performing baseline measurements for 20 min in the overnight fasting state, the subjects swallowed the ten 20‐mL test drinks over a 5‐min experimental period in three ways on different days. In the control trial (C trial), subjects swallowed one 20‐mL test drink immediately every 30 s. In the long‐duration stimulation trial (D trial), subjects kept the 20‐mL test drink in their mouth for 30 s without mastication, and then swallowed it. In the masticatory stimulation trial (M trial), subjects masticated the 20‐mL test drink for 30 s (at a masticatory frequency of once per second), and then swallowed it. Oxygen uptake was measured until 90 min after the last test drink was swallowed, and this was converted into the energy expenditure. DIT was calculated from the body mass and increments of energy expenditure after swallowing the test drink relative to the baseline obtained before the start of each trial (Sekino et al. 2010, Toyama et al. 2015). Substrate oxidations of protein, fat, and carbohydrate were calculated from the oxygen uptake and carbon dioxide output using the formulas from the previous studies (Weir 1949, Jéquire and Felber 1987). Protein oxidation was assumed to constitute 15% of the energy expenditure (Tentolouris et al. 2008). The DIT accumulated over 90 min after swallowing the test drink was significantly greater in the M trial than in the C and D trials (mean±SEM: C trial, 43±5 cal/kg; D trial, 75±9 cal/kg; M trial, 107±12 cal/kg). The substrate oxidations of protein, fat, and carbohydrate accumulated over 90 min after swallowing the test drink did not differ significantly among the three trials (C, D, and M trials: protein oxidation, 55±1, 56±1, and 57±1 mg/kg, respectively; fat oxidation, 43±2, 40±4, and 42±4 mg/kg; carbohydrate oxidation, 216±9, 228±13, and 228±15 mg/kg). These results indicate that the duration of stimulation to the oral cavity and mastication both increased DIT, while the substrate oxidation of macronutrients was not affected. Therefore, increasing the stimulation to the oral cavity can enhance DIT, implying that such stimulation can be helpful for weight management.Support or Funding InformationThis work was supported by JSPS KAKENHI Grant Number 15J11944.
Impact of Mitochondrial Free Fatty Acid Overload on Hepatic Ureagenesis in Mice with Nonalcoholic Steatohepatitis
Authors: Kalavalapalli Srilaxmi , Abdo Kaitlyn I , Murphy Zachary J , Fernandez Jose C , Cusi Kenneth , Sunny Nishanth E 
Published: November 2023

Defects in ureagenesis are observed in several animal models with dysfunctional mitochondrial fat oxidation. The metabolic pathway of urea cycle, responsible for nitrogen disposal spans the mitochondrial and cytosolic compartments of the hepatocyte. Considering the central role of mitochondrial dysfunction in the etiology of fatty liver disease, we hypothesized that prolonged free fatty acid (FFA) overload and nonalcoholic steatohepatitis (NASH) will impair the flux through the urea cycle. To test the impact of FFA on ureagenesis, isolated primary hepatocytes from normal mice were cultured and incubated in custom media with low (0.25mM) and high (0.8mM) FFA. Urea concentration in the custom media was measured after 30mins, 3hr and 6hr incubation periods of hepatocytes by GC‐MS. Further, mice (C57/BL6) were kept on Control diet or high fructose high trans‐fat diet (TFD) for 24‐weeks to induce NASH, which was confirmed by histology. Urea turnover rates were determined after infusion of [15N2]urea stable isotope tracer followed by gas chromatography and mass spectrometry (GC‐MS) analysis. Liver tissues of these mice were used to quantify mRNA expression of genes involved in urea cycle. Increasing FFA concentration resulted in higher rates of urea production in isolated hepatocytes. However, onset of NASH did not alter urea turnover rates (Controls: 1.84 ±0.07 vs. NASH: 1.83 ±0.14 μmoles/min) in mice despite an induction of tricarboxylic acid (TCA) cycle activity (Controls: 2.62 ±0.47 vs. NASH: 5.39 ±0.59 μmoles/min). In spite of unaltered urea turnover, expression of genes involved in urea cycle (CPS1, ARG1, ASL, and ASS1) was significantly reduced in mice with NASH. Our results demonstrate that, while a physiological increase in FFA and TCA cycle activity could stimulate ureagenesis, onset of NASH disrupts urea cycle activity. Dysfunctional ureagenesis in animals with non‐alcoholic steatohepatitis unravels a complex association between protein and FFA metabolism and may provide a snapshot into hepatic mitochondrial dysfunction.Support or Funding InformationResearch Opportunity Seed Fund Award, UF (N.S.)
Intaken CHO/Fiber as Diagnostic Tool for Diet Quality and Prognostics of Insulin Resistance in Free‐living Adults
Authors: Bernardino Caroline , Corrente José Eduardo , Burini Roberto Carlos 
Published: November 2023

Insulin resistance is closely associated with ingested single sugars and refined cereal products, all evaluated as carbohydrate (CHO) intake. In the same category are the dietary fiber and its sources, with different impact on insulin resistance. The CHO/Fiber ratio would provide an indirect form to check the actual sugar consumption. This study aimed to establish the relationship of CHO/Fiber with the plasma HOMA‐IR, metabolic syndrome and dietary quality of adults enrolled in a Lifestyle Modification Program. In a cross‐sectional study, baseline data from 600 subjects (80% females) over 35 yrs old (54.6 ± 11) participants of an ongoing dynamic cohort study (“Move for Health”) were retrospectively collected (2007–2014). They were analyzed for their diet quality (Health Eating Index‐HEI) and food intake (24h recall) in relation to the co‐variables gender, age, anthropometry, plasma biochemistry, blood pressure and presence of Metabolic syndrome (ATP III‐NCEP). Data were divided in quartiles. ANOVA one way, Tukey's post hoc and Linear multiple regression were applied to analyze the influence of co‐variables in the CHO/Fiber ratio (p<0.05). The calculated quartiles for CHO/Fibers were Q1 <9.75(23.7±10.8g/d fibers); Q2 = 9.75–13.05(17.9±8.2g/d fibers); Q3=13.05–18.97(13.1±6.0g/d fibers) and Q4 >18.97(8.3±3.8g/d fibers). CHO/Fiber ratio showed a significant positive linear regression with the daily serving sugars (r=1.74, p=<0.001) and cereals (r=0.72, p=0.03) and negative with body weight (r= −0.08, p=0.017), serving legumes (r= −0.79, p= 0.01) and HEI (r= −0.20, p=<0.001). When adjusted by age, gender, BMI and kcal/day, Q1 was discriminated by the fewer servings of sugar, higher servings of legumes and higher HEI score. Q1 showed also lower HOMA‐IR than the other quartiles. However, with any other significant relationship of Q1 with the presence of metabolic syndrome and neither with its components. Thus, from the found results the CHO/Fiber ratio seems a single tool suitable for diagnosing poor quality CHO‐diets associated with insulin resistance marker.Support or Funding InformationSupported partially by CAPES and CNPq.
Association between obesity and amino acids: a metabolomics approach
Authors: Marchioni Dirce , Carioca Augusto Antonio , Miranda Andreia Alexandra , Carvalho Aline Martins , Steluti Josiane , Cotrim Ismael Dale , Silva Alexsandro Macedo , Fisberg Regina Mara 
Published: November 2023

Obesity has reached epidemic proportions in many countries around the world and is strongly linked to a number of chronic diseases. Some amino acids, such as three branched amino acids and glutamine, are associated with metabolic disorders. The interaction between obesity and amino acids is complex and not yet fully elucidated. The metabolomics can be a useful tool for solving some of these metabolic disorders. The aim was to investigate the association between amino acids and obesity.MethodsData came from a population based cross‐sectional survey in Sao Paulo among 169 adults. A trained research nurse measured body weight, height and waist circumference (WC) using a standardized protocol. BMI was calculated by dividing weight (kilograms) by the square of height (meters). Obesity was determined based on BMI ≥ 30 kg/m2. The branch chain amino acids (BCAA) are the sum of the valine, leucine, and isoleucine. The glutaminolysis ratio (Gluta Ratio) is (alanina+ aspartate + glutamate)/glutamine. Quantification of the metabolites was performed by mass spectrometry of the type targeted. Multiple linear regression models were performed to verify the association between amino acids (BCAA and Gluta ratio) and BMI or WC, adjusted for age, sex, energy intake, race, smoking, physical activity.ResultsThe sample was comprised of 52% men, 60% adults and mostly of white race (57%). The BMI was associated with BCAA (β=8.57; p<0.001) and Gluta Ratio (β=0.02; p<0.001). The WC was associated with BCAA (β=3.92; p<0.001) and Gluta Ratio (β=0.01; p<0.001). The concentration of BCAA (β = 82.67, p <0.001) and Gluta ratio (β = 0.211, p <0.001) were higher in obese subjects compared with non‐obese.ConclusionObesity was associated with three branched amino acids and glutamine metabolism.Support or Funding InformationCNPq grant 473778/2010‐6 and FAPESP grant 2011/19788‐1
A Minimal Compartmental Model for the Assessment of Net Whole Body Protein Breakdown, Using a Pulse of Phenylalanine and Tyrosine Stable Isotopes in Humans
Authors: Mason Alvise , Engelen Marielle , Toffolo Gianna , Deutz Nicolaas 
Published: November 2023

RationaleWe recently developed a novel and easy‐to‐use approach to measure net whole body protein breakdown (netPB), using non‐compartmental modelling after single pulse injection of the stable isotopes phenylalanine (PHE) and tyrosine (TYR). We further fine‐tuned this approach by developing a minimal compartmental model to add structural information to amino acids kinetics in PB with high precision.MethodHealthy human subjects (8 male, 6 female, age: 59.6 ± 9.0 years) were given in the post absorptive state a single pulse (8ml) injection of L‐[ring‐13C6]PHE (6.44 mg/ml) and L[ring‐2H4]TYR (0.46 mg/ml). Multiple plasma samples were collected for 120 min and tracer‐tracee ratio of PHE (mass 6) and TYR (mass 4 and 6) were measured by LC‐MS/MS. A four compartment model was developed to describe the kinetics of PHE and TYR and the PHE to TYR hydroxylation. The model is a priori identifiable from the PHE‐6 and TYR‐6 data measured following the PHE‐6 injection, provided that the TYR‐6 accessible pool size is known. Since this pool represents plasma and rapidly equilibrating tissues (mainly the liver) where the PHE to TYR interconversion takes place, its pool size was assumed to be equal to 25% of the whole body TYR pool size, estimated from the TYR‐4 decay curve. The model, identified by using SAAM, was able to reproduce the experimental data of all individuals, and all its parameters were estimated with high precision (VC%: 14.78 ± 7.77). Our model provides estimates of compartmental fluxes, including the plasma appearance of PHE and TYR, and the PHE to TYR interconversion. These fluxes were compared to their counterparts, estimated via non‐compartmental analysis in order to assess the physiological relevance of the estimated variables.ResultsThe following data were obtained by non‐compartmental versus compartmental analysis for Net‐PB (6.998 ± 2.237 umol/FFM kg/h, versus 6.475 ± 1.899 umol/FFM kg/h, resp.), rate of appearance of PHE (53.626 ± 7.479 umol/FFM kg/h versus 49.675 ± 5.137 umol/FFM kg/h, resp.), rate of appearance of TYR in plasma (44.686 ± 9.012 umol/FFM kg/h versus 45.879 ± 9.110 umol/FFM kg/h, resp.). These data suggest that our model is physiologically meaningful.ConclusionOur data reveal that after single pulse injection of PHE and TYR stable isotopes, a minimal compartmental model analysis estimates net PB with low variability when the physiology of PHE to TYR conversion is included in the model estimations. Furthermore, our model may provide more detailed insight in the metabolism of these amino acids.
Whole Body Protein Turnover in Overweight/Obese Adults in Response to Whole Grain and Refined Grain Diets – A Randomized Control Trial
Authors: Kirwan John P , Ross Alastair B. , Kullman Emily L , Malin Steve K , Scelsi Amanda , Kochhar Sunil , Godin Jean‐Philippe 
Published: November 2023

Data from several intervention studies suggest that whole grains (WG) lead to increased fat loss and enhanced metabolic function compared to control diets. Abnormalities in energy balance and protein metabolism, including protein flux, protein synthesis and protein breakdown, are part of the obesity phenotype and may be amenable to change by altering nutrient intake using a WG enriched diet. We hypothesized that a whole grain enriched diet would alter protein metabolism and total energy expenditure (TEE), and thus contribute to increased muscle mass and a decrease in fat mass. We performed a double‐blind crossover diet intervention study to examine the effects of a WG‐based diet on protein kinetics, TEE and body composition, compared to a calorie matched control diet (refined grain (RG)). Complete diets were provided to subjects, based on nutritional guidelines for fat, protein (1.05 g/kg/day) and carbohydrate, with either WG (50g/1000 kcal) or equivalent RG. Fourteen overweight/obese (BMI 32.9 ± 4.5 kg/m2) adults (age 39 ± 7 years) participated in the trial. Each diet was provided for 8 weeks, with a 10‐week washout between diet arms. TEE was assessed by doubly labeled water (2H218O), whole body protein turnover was assessed using a stable isotope approach (oral dose of 15N‐Glycine), and body composition was determined from DEXA measures. After 8 weeks of WG and RG diet, changes in body weight and fat free mass were similar for both diets. Likewise, TEE did not differ between the diets (~2147 ± 291 kcal/day). Protein synthesis was 3.7 ± 0.5 g protein/kg/day for both diets (P>0.05), while protein breakdown was 4.7 ± 0.5 and 4.9 ± 0.4 g protein/kg/day for WG and RG diets, respectively. For protein balance the values were −1.03 ± 0.05 and −1.1 ± 0.1 g, protein/kg/day for WG and RG diets (P>0.05), respectively. Rates of protein synthesis, breakdown and nitrogen balance were higher after the WG diet when expressed relative to FFM, but protein turnover was similar for effects between diets. We conclude that 8 weeks on a WG diet does not produce significantly different changes in body composition, TEE, or whole body protein metabolism, when compared to a calorie matched control diet.Support or Funding InformationInvestigator‐initiated grant, Nestlé; NIH UL1RR024989 and T32 DK007319.
Microfluidic Systems for Stem Cell Studies
Authors: Tayebi Lobat 
Published: November 2023

Stem‐cell therapies have the potential to revolutionize the healthcare. Microfluidic‐assisted systems can be used for cell‐based assays to provide unique information about the cellular behavior of stem cells. The significance of microfluidic platforms is their ability to mimic the in vivo microenvironment. Moreover, using microfluidic systems, the quantity and level of different agents and cell stimulator factors can be controlled. Such precise controlling is highly important for stem cell culturing and differentiation.It is known that to employ stem cells in clinical applications, the key challenge is scaling up the cultures in large bioreactors for master banking of stem cells to be used for treatment of patients. Thus, small microfluidics system is useless for this purpose. However, many technical problems in the important task of controlling stem cell growth and differentiation can be answered using the precise microfluidic systems.In this talk, after presenting a discussion on the application of microfluidic platforms in stem cell culturing and differentiation, the latest developed microfluidic systems for stem cell study will be introduced. This includes our group's recent innovation in designing a microfluidic platform for regulating the osteogenic differentiation of mesenchymal stem cells (MSCs).
Effects of Obesity on Serum and Hepatic Cations in Zucker Rat Model
Authors: Hakkak Reza , Korourian Soheila , Niedoba Matthew , Romani Andrea 
Published: November 2023

Obesity has been epidemic in the United States for more than two decades. Obesity is associated with type 2 diabetes, cardiovascular disease and certain types of cancer. We investigated the effect of obesity on serum and liver cations. Five‐week‐old female lean and obese Zucker rats were used. After one week of acclimation, Lean and Obese rats were maintained on AIN‐93 G diet for 155 days and serums and livers were collected. Different cations were measured by atomic absorbance spectrophotometry in addition to protein content. Obese rats gained significantly (P<0.001) more weight than lean rats. Obesity caused; 1) a significant increase in serum protein (P<0.05) but not in hepatic protein content, which was decreased (p<0.05); 2) a significant increase in total serum Ca2+ levels (p<0.05) but not in total hepatic Ca2+ content, which was significantly decreased (p<0.05); 3) a decreased in serum K+ level (P<0.05) but an increase in liver K+ content (p<0.05), and 4) a decrease in serum Mg2+ vs. an increase in liver Mg2+ content (p<0.05). As a consequence, the hepatic Mg2+/Ca2+ ratio in obese animals was three time higher as compared to the lean counterpart. In contrast, the Mg2+/Ca2+ ratio in the serum of the obese animals was about 25% lower as compared to the ratio in the lean animals. The effects of the obesity and these changes in cation content and Mg2+/Ca2+ ratio on the expression of key metabolic liver enzymes are currently under investigation. In summary, our results show that serum can be a good predictor of several intracellular cations levels compared to liver. The implications of these cation changes on liver metabolism and ER stress are in need of further clarification.Support or Funding Information(Supported by CUMG and ABI grants to RH).
Associations between dietary macronutrients, glucose and insulin dynamics in obese adolescents
Authors: Braun Ethan , Wagner Kelly , Armah Seth , Smith Lisa , Boushey Carol , Delp Edward , Hannon Tamara , Gletsu‐Miller Nana 
Published: November 2023

ObjectiveModifiable risk factors of type 2 diabetes (T2D) include dietary factors which impact glycemia, but there have been few investigations in adolescents. We aim to determine associations between diet and measures of glucose and insulin dynamics in adolescents who are obese.Research Design and MethodsCross‐sectional, baseline measures were obtained from an ongoing, randomized controlled intervention to prevent T2D in obese adolescents. Dietary intake was assessed for four days using mobile phone technology to create an electronic food record. Glucose and insulin dynamics were assessed during a 2‐hour oral glucose tolerance test. Multiple linear regression was used to assess the associations between macronutrient intake and measures of glycemia and insulin.ResultsFifteen obese participants (67% female, BMI 34.9 kg/m2) were screened and 47% had prediabetes. Anthropometric measures were similar between youth with prediabetes and youth with normal glycemia. Dietary fat intake was associated with concentrations of glucose at 2 hours (β=1.3, P= 0.006), insulin sensitivity (β= −1.5, P= 0.002), and beta‐cell function (β= −1.6, P= 0.0009); total fiber intake was associated with concentrations of glycosylated hemoglobin (β= −0.57, P= 0.04).ConclusionsDietary intake of fat and fiber were associated with glucose and insulin action and may serve as targets for future interventions for prevention of T2D.Support or Funding InformationThis work was supported in part by a Project Development Team within the ICTSI NIH/NCRR Grant Number UL1TR001108. Other support included funding from Riley Hospital for Children Indiana University Health, and the Center for Pediatric Obesity and Diabetes Prevention Research.
Untargeted Metabolomic Profiles, Childhood Obesity, and Metabolic Risk in the ELEMENT Cohort
Authors: LaBarre Jennifer , Perng Wei , Karnovsky Alla , Tang Lu , Song Peter , Burant Charles F. , Cantoral Alejandra , Peterson Karen E. , Téllez‐Rojo Martha Maria 
Published: November 2023

ObjectiveTo use metabolomics data quantified on an untargeted platform to identify metabolic alterations associated with obesity during childhood, and to examine the relations of these metabolite patterns with conventional cardiometabolic biomarkers.MethodsUntargeted metabolomic features were analyzed using liquid chromatography/mass spectrometry in fasting serum from 250 children enrolled in the Early Life Exposure in Mexico to ENvironmental Toxicants (ELEMENT) Project, a birth cohort study. ELEMENT participants aged 8–13 years were selected for this analysis based on availability of archived biomarkers in serum and cord blood required for a separate study. We used Principal Component Analysis (PCA) to consolidate 4652 metabolite features into factors based upon their inter‐correlations. To determine how obesity status corresponded with differences in circulating metabolites, we compared factors scores for obese (body mass index [BMI] z‐score ≥2; n=46) and normal weight (−2≤ BMI z‐score <1; n=119) children. Metabolite clusters associated with obesity were retained for further investigation. Among all participants, we used multiple linear regression to estimate the relationship between metabolite factor scores and conventional biomarkers of metabolic risk: high density lipoprotein (HDL), low density lipoprotein (LDL), total cholesterol, triglycerides, fasting glucose, and leptin.ResultsMedian age was 10.0 years; 47.6% were boys. Our sample included 46 obese (18.4%), 81 overweight (32.4%), 119 normal weight (47.6%), and 4 underweight children (1.6%). As compared to normal weight children, obese children had a higher score for Factor 2, which largely comprised of amino acids and modified fatty acids. After accounting for sex, maternal education, and pubertal stage, each unit increment in Factor 2 corresponded with 5.54 (95% CI: 2.18, 8.90) mg/dL higher total cholesterol, 4.25 (95% CI: 1.51, 7.00) mg/dL higher LDL, and 6.43 (95% CI: 0.94, 11.93) mg/dL higher triglycerides.ConclusionsIn this sample of peripubertal Mexican children, an amino acid and modified fatty acid metabolite pattern associated with obesity was also related to an adverse lipid profile. Future longitudinal studies are warranted to ascertain temporality.