bluuebunny/crossref_metadata_2025 huggingface dataset:
Pasteurella multocida toxin (PMT) activates the ERK signaling pathway, in part, by upregulating CTGF expression
Authors: Oubrahim Hammou , Sengupta Deepali C. , Wilson Brenda A. , Chock P. Boon
Published: June 2021

PMT, a 146 kDa bacterial protein, is a potent mitogen and a strong inducer of anchorage‐independent growth for fibroblast and osteoclast cells. We showed that PMT activated the ERK pathway, and that this ERK activation was also detected when quiescent 3T3 cells were treated with conditioned media taken from PMT‐treated cells. These results support the existence of a diffusible factor(s) that mediates ERK activation. Microarray analysis revealed that connective tissue growth factor (CTGF) is the most elevated factor in PMT‐treated cells. CTGF is a 36‐kDa secreted protein and a member of the CCN family. It stimulates cellular proliferation and regulation of angiogenesis and tumorigenesis. Western blot analysis using CTGF antibody revealed a robust elevation of an immunoreactive protein of 36–38 kDa in both cell lysate and conditioned media of PMT‐treated cells. This observed PMT‐induced CTGF elevation was also detected in WT, but not in Gαq/Gα11‐deficient MEF cells. While PMT failed to induce ERK activation in Gαq/Gα11‐deficient MEF cells, the conditioned media can activate ERK in these cells suggesting that PMT upregulates the CTGF protein level and leads to ERK activation.

This work was supported, in part, by the Intramural Research Program of the NIH, NHLBI.
Initial evidence for increased glutamine turnover in obese adolescents
Authors: Lenders Carine M ,   The Elisabeth Glaser Pediatric Research Network Obesity Study Group
Published: June 2021

Objectives

To examine the relationships of plasma glutamine‐to‐glutamate ratio (Gln/Glu) to markers of energy metabolism and body fat.

Methods

58 obese 13–17.9 years olds, screened for a Weight‐Loss Trial (38 females, 8 black, 16 Hispanic). We calculated FM using DXA‐scan and VAT using CT‐scan. Blood tests included amino‐acids (AA), 25(OH)D, and PTH. HOMA_IR calculated based on fasting glucose and insulin levels.

Results

Median [10–90th percentile] plasma levels included glutamine 524[432;595], glutamate 56[26;98], their ratio 10[5;22], leucine 21[102;151], and BCAA 428[354;505] μmol/L. After adjusting for age, sex, race/ethnicity, Tanner stage, 25(OH)D deficiency, and PTH, Gln/Glu was inversely associated with HOMA_IR (−0.13±0.06 units, p=0.004). After adjustment for covariates including HOMA‐IR, Gln/glu was inversely associated with VAT (−0.2±0.1%), FM (−628±218g) and BMI (−0.3±0.12kg/m2), p<0.05; not lean mass (p>0.05).

Discussion

While leucine, BCAA, and glutamine levels were similar to Lepage data (1997), glutamate was more than twice as high. Thus, Gln/Glu was half that of healthy adolescents and inversely related to energy metabolism and body fat measures. These results provide initial evidence of increased glutamine turnover in obese adolescents. K23DK082732‐01.
Central and Peripheral Administration of Compound 21 Elicits Cerebroprotective Effects in Ischemic Stroke
Authors: Joseph Jason P , Regenhardt Robert W , Mecca Adam P , Patel Neal A , Steckelings Ulrike M , Unger Thomas , Katovich Michael J , Sumners Colin
Published: June 2021

Studies indicate that angiotensin type 2 receptors (AT2R) in the CNS exert beneficial actions in ischemic stroke. Here we tested the effects of a specific AT2R agonist, Compound 21 (Cp21), on the cerebral deficits produced by endothelin‐1 induced middle cerebral artery occlusion (MCAO). Adult male Sprague Dawley rats were pre‐treated with Cp21 (0.0075μg/h) or artificial cerebrospinal fluid (aCSF) via intracerebroventricular infusion for 7 days prior to ET‐1 induced MCAO. Cp21 treatment reduced neurological deficits and infarct size measured 72 h after MCAO induction. Infarct size was reduced to 28.2±4.0% of ipsilateral gray matter in Cp21‐treated rats (n=16) compared with 54.1±4.7% in aCSF controls (n=21; p=0.0006). Neurological deficits were reduced by Cp21 treatment as indicated by a lower Bederson Exam Score of 0.3±0.1 compared to 1.6±0.2 in control rats (p<0.0001) and a higher Garcia Exam Score of 16.9±0.3 compared to 14.3±0.7 in control rats (p=0.0011). Similar results were obtained with the IP administration of Cp21. Rats received IP injections with Cp21 (0.03 mg) or 0.9% saline at 2 hours prior, and 4, 24, and 48 hours following MCAO induction. Infarct size was reduced to 19.2±3.8% of ipsilateral gray matter in Cp21 treated rats (n=6) compared with 41.5±6.8% in saline controls (n=6; p=0.004). These data are the first demonstration of a non‐peptide AT2R agonist exerting cerebroprotection following MCAO.
Automating the Visualization of Biological Machines
Authors: bajaj chandrajit lal
Published: June 2021

With continued advances in three dimensional Electron Microscopy one is progressively able to elucidate and visualize natureˈs biological molecular machines (e.g. ribosomes, viruses) at varying resolutions and different conformations. I shall first discuss a suite of geometric optimization methods to automatically reconstruct a 3D volumetric model from a set of 2D images of the same object but with unknown pose. The solution to the inverse problem utilizes a pose determination algorithm, variational reconstruction of 3D scalar functions from 2D images, and geometry/image processing techniques of structure interpretation, feature extraction, and model refinement at progressively finer resolutions. Next, Ill briefly discuss molecular modeling techniques that enable dynamics, and visualization of structure‐function relationships of these biological machines.
Biological evaluation of cyclized cystine knot peptides targeting human melanocortin receptors
Authors: Bao Jennifer , Cai Minying , Craik David , Hruby Victor
Published: June 2021

Because of their multiplicity and ubiquity in mammalian systems as central modulators of signaling, GPCRs have held a special interest in drug design. Specifically, ligands targeting the homeostatic class of GPCRs known as melanocortin receptors (MCRs) have the potential to remedy the symptoms of obesity, diabetes, and pain. Adenylate cyclase assays were performed on HEK 293 cells expressing hMC1R, hMC3R, hMC4R, and hMC5R to assess a class of 39 multiple‐disulfide, cyclized MSH analogues featuring strategic N‐methylation and based on the protein topology of conotoxins found in the venoms of marine cone snails. Because of their potency and selectivity, conotoxins offer a promising avenue for drug design; furthermore, the combined cyclic backbone and cystine knot motifs of the MSH conotoxin analogues afforded specific conformational constraining in addition to enhanced proteolytic stability and bioavailability. Several antagonists of hMC4R and agonists of hMC5R were identified from the library with EC50 values in the low micromolar range; these results provide important starting points for further optimization. This research was supported by the PHS (DK17420), NIH (DA06248), and HHMI (52003749).
MG53 reduces cell death associated with hemorrhagic shock ischemia/reperfusion (I/R) injury by increasing membrane repair capacity
Authors: Moloughney Joseph Gennaro , Hersey John , Tan Tao , Hsai Henry , Weisleder Noah
Published: June 2021

Physical trauma is a leading cause of death in the United States. While interventions to restore blood pressure and volume following acute trauma are essential, the abrupt restoration of blood flow following ischemia results in significant cell damage and death. As a result, injury caused by a hemorrhagic shock ischemia/reperfusion (I/R) event can have severe consequences, including organ failure and patient death. MG53 is a TRIM family protein which is an essential component of the cell membrane repair machinery in cardiac and skeletal muscle. Following various types of membrane damage, including injury associated with I/R, our research group has shown that MG53 facilitates formation of a membrane repair patch to restore the integrity of the disrupted membrane. Creatine kinase (CK) and lactate dehydrogenase (LDH) assays revealed significantly increased membrane resealing capacity in cultured mammalian cells or isolated mg53−/− flexor digitorum brevis (FDB) muscle fibers in the presence of rhMG53. Histological examination of tissue isolated from mice pretreated with rhMG53 and subjected to hemorrhagic shock reveal a significant decrease in Evan's blue dye staining in multiple tissues, suggesting reduction in necrotic cell death due to enhanced membrane repair. Our results show that recombinant human MG53 (rhMG53) can serve a protective role and mitigate cellular death and damage brought on by I/R following hemorrhagic shock. Research was funded by the Foundation for UMDNJ.
Characterization of Novel Anti‐androgens as Potential Prostate Cancer Therapeutics
Authors: Jobbagy Soma , Mantravadi Pavan Kumar , Sikes Robert , Koh John
Published: June 2021

Anti‐androgens are the gold standard of care for treatment of advanced prostate cancer (PCa). The purpose of this study was to assess novel anti‐androgens PLM1, PLM6, and PAN52 designed and synthesized in the Koh laboratory. These compounds are based on the clinical standard bicalutamide, but have expanded aryl sulfonyl moieties. PLM6 and PAN52, but not PLM1, are thought to have unique mechanisms of action based on their ability to evade progression to anti‐androgen insensitivity in vitro. Prevention of androgen receptor (AR) nuclear translocation was found to correlate with evasion of anti‐androgen resistance in prostate cancer cell lines. Furthermore, these novel anti‐androgens were found to down‐regulate the androgen receptor, which may contribute to their efficacy. Statistically significant increases in prostatic apoptosis were observed in C57/Bl6 mice treated intraperitoneally with PLM6 and PAN52, indicating that these compounds hold promise as therapy for advanced prostate cancer. Motivated by these findings, we are exploring compounds with increased potency.
Development and validation of a quantitative FFQ for Guam
Authors: LeonGuerrero Rachael Taitano , Novotny Rachel , Wilkens Lynne , Chong Marie
Published: June 2021

The purpose of this study was to develop a food frequency questionnaire (FFQ) to assess dietary intake over 12 months. A cross‐sectional study of Guam residents (n=127), aged 25–65 years, was conducted using 24‐hour diet recalls. A complete list of all foods and beverages recorded by the 24‐hour recalls of this study served as the draft for the FFQ. The final FFQ contained 142 food and drink items. In order to test the validity of the FFQ, 59 individuals from Guam were asked to complete the FFQ and a 2‐day food record. Once all food records and FFQs were administered, nutrient intake for the food records and FFQs were computed. All food record and diet recall data were coded, entered and analyzed using Pacific Tracker Program, 4th edition. A food composition table was constructed specifically for the 142‐item FFQ; and then the daily nutrient intake of each of the 142 FFQ food items was determined for each of the 59 subjects. Similar mean daily nutrient intake was derived from the food recalls and the 142‐item FFQ. This instrument will be a useful tool in the analysis of diet‐cancer associations in Guam and the Mariana Islands. This study was funded by a NCI MI/CCP Grant #1056‐CA‐096278‐01A1 and #U54‐CA‐143727.
Alternative Healthy Eating Index (AHEI) and its association with adequate intake and nutritional status in HIV+ adults
Authors: Campa Adriana , Hernandez Gabrielle , Martinez Sabrina Sales , Li Yinghui , Lai Shenghan , Page John Bryan , Baum Marianna K
Published: June 2021

Objective

A low Alternative Healthy Eating Index (AHEI) is associated with risk of chronic diseases and may be a useful tool in predicting risk of HIV progression. This study examined the relationship between AHEI, nutritional status and dietary intake in HIV+ adults.

Methods

In a cross‐sectional study of 202 HIV+ adults, the AHEI (scored on the basis of intake of 8 components: vegetables, fruit, nuts and soy, white or red meat, polyunsaturated or saturated fat, fiber, multivitamin use, and alcohol) was applied to 24‐hour recalls. Regression analyses assessed the relationship between AHEI score and nutritional and immunological biomarkers collected simultaneously.

Results

The AHEI score was significantly inversely related to viral load (β=−1.023, p=0.0108), and directly to body cell mass (β=0.06, p=0.03), serum albumin (β=1.82, p=0.03), hemoglobin (β=0.50, p=0.045), iron intake (β=0.12, p=0.0002) and adequate caloric intake using the Harris‐Benedict formula (β=0.001, p=0.003). The models were controlled for BMI, age and education.

Conclusion

AHEI is significantly associated with viral load, a marker of HIV disease progression, and with parameters of nutritional status and dietary intake. The Healthy Eating recommendations that are the basis of the AHEI, should be an important part of nutritional interventions for people living with HIV.

Funded by NIDA
Comparison of the InBody 520 bioimedance analyzer to air displacement plethysmography for body composition measurements in a healthy adult population
Authors: Barber Anjee , Hobb Kylee , Kern Mark
Published: June 2021

A variety of methods of body composition techniques have been developed; however, an inexpensive, accurate, and portable technique to measure body composition is important for many applications. The purpose of this study was to compare the InBody 520 (IB‐a multisite, multi‐frequency BIA machine) to a relatively strong criterion laboratory‐based air displacement plethysmography instrument (BodPod, BP). One hundred one adults aged 31.1± 12.0 years (56 men, 45 women) participated. Participants were tested on each instrument on the same morning following manufacturer‐based preparation suggestions. Results revealed differences (p<.05) in percent body fat (22.3%±8.5 and 17.9%±7.9), fat mass (16.0 ±7.6 kg and 13.2±8.3 kg), and lean mass (55.3 ±11.8 kg and 58.3 ±12.1 kg) for BP and IB, respectively. However, correlations (p<.05) between the instruments were high for percent body fat (r=.901), fat mass (r=.871) and lean mass (r=.972). More variability was apparent in overweight individuals, although when those subjects were deleted from analyses, statistically significant differences persisted.
Alternatives for energy‐adjustment of nutrient intakes
Authors: Rhee Jinnie , Cho Eunyoung , Willett Walter
Published: June 2021

Objective

Adjustment for body weight and physical activity has been suggested as an alternative to adjusting for reported energy intake. We examined which of these approaches would yield stronger correlations between nutrients and their corresponding blood biomarkers.

Methods

We used data from nested case‐control studies of erythrocyte fatty acids and coronary heart disease (N=442), and of plasma carotenoids and breast cancer (N=1254). Dietary fatty acids and carotenoids were adjusted for total energy intake estimated by food frequency questionnaire and, separately, for body weight and physical activity. We computed correlation coefficients between the adjusted nutrients and their biomarkers.

Results

Energy‐adjusted trans fatty acid intakes had significantly stronger correlations with blood biomarkers than did intakes adjusted for weight and activity (for plasma fatty acid levels, r=0.17 unadjusted, 0.30 energy‐adjusted, and 0.16 weight‐ and activity‐adjusted; for erythrocytes, the corresponding correlations were 0.25, 0.37, and 0.25). For intakes of linoleic acid and alpha‐linolenic acid, correlations with their respective biomarkers were also significantly stronger when adjusted for reported energy intake than when adjusted for weight and activity. Adjustments made little difference for docosahexaenoic acid and carotenoids.

Conclusions

Adjustment for energy intake calculated from the same questionnaire used to estimate nutrient intakes appears to be superior to adjustment using body weight and physical activity. This work was supported by the National Institutes of Health [AG00158].
The Local Prevalence of Vitamin D Deficiency or Insufficiency in Southeast Michigan
Authors: Duanmu Zhengbo , Shah Rita P , Reddy Vishnuvardhan , Shah Alka Y , Marella Basil J , Gupta Neelum , Roth Frank , Knapp Mary J , Shah Dinesh M
Published: June 2021

Serum 25(OH) vitamin D level is critical for optimal health. Vitamin D deficiency is associated with skeletal abnormalities as well as numerous other health issues. The objective of this study was to evaluate by age and gender the local prevalence of vitamin D deficiency and insufficiency in a population from an area of Northern latitude (Southeast Michigan). This was a retrospective cohort study of 1016 patients with serum vitamin D measurements from December 2010 to June 2011. Vitamin D level were normal in 323 patients (31.8%), insufficient in 337 patients (33.2%) and deficient in 356 patients (35.0%). The average vitamin D levels in both male and female were below normal (24.8±13.2 and 27.5±13.2 respectively). Contrary to other reports, our results showed vitamin D levels increased with age. For patients age >60, 30–59, and <30, the average 25(OH) D levels declined considerably from 28.9±13.9, 22.9±11.5, to 17.6±7.6, respectively (P<0.001 among each group). Consistent with previous investigations, these findings suggest a high prevalence of vitamin D deficiency and insufficiency. The serum 25(OH) D levels were markedly lower in males compared to those in females. Surprisingly, serum 25(OH) D levels were lowest in the younger population. Current recommendations for vitamin D supplementation may need to be adjusted accordingly based on these results.

Supported by Michigan Physicians Group internal funding.
Child characteristics drive parental feeding practices in African American and Latino parents
Authors: Quesada Catalina , Lora Karina , Wakefield Dorothy , Ferris Ann
Published: June 2021

This study explored how child characteristics drive parental feeding practices in African American (AA) and Latino parents of 3–5 y children. Cross‐sectional study conducted at schools in Hartford, CT included 205 parents (123 AA, 82 Latinos). Participants provided demographic information and completed Preschooler Feeding Questionnaire (PFQ) (Baughcum et al, 2001). Factor analysis of PFQ retained eight factors for 31 questions. Kruskal Wallis tests compared PFQ factors of “picky” and “non picky” eaters. Multivariate regression models examined PFQ factors by child characteristics. Picky eaters scored lower on concern about child overeating or being overweight (factor 2) and structured feeding interactions (factor 7); and higher on concern about child being underweight (factor 5), child centric feeding and use of rewards (factor 6), and age inappropriate feeding (factor 8) (P<.05). In multivariate models, parents of children with higher BMI reported higher factor 2 and lower factor 6. Parents of “picky” eaters reported higher scores on factor 5, 6, and 8 (P<.05). Latino parents reported higher use of factor 6 and 8 than AA parents. Parents of preschool girls reported lower factor 4 (use food to calm child) and 6 than parents of boys. In this sample, child characteristics influence parental feeding practices, which may play important role in child's weight control.
Incongruence between mother perceptions and preschooler's actual weight status using BMI Categories
Authors: Lindsay Anne , Hite Alicia , Byington Teresa , Lu Minggen , Sigman-Grant Madeleine
Published: June 2021

Mothers of overweight or obese children are reported to underestimate their child's weight status. This study assessed how accurately a mother perceived her preschooler's body size and the affect of the child's actual weight status (underweight, healthy weight, overweight or obese BMI) on this perception. The study also included the mother's perception of her own body size. Both mothers and their children ages 3–5 y (n=265) attending one of 12 Las Vegas Nevada Head Start centers were weighed, measured and interviewed. Mothers (74.3% Hispanic) indicated their own and their child's silhouettes. Although 72.8% correctly identified their own body size, only 55% of mothers were accurate in identifying their preschooler's body size. When looking at the preschooler's weight status, 83% of mothers with children in the “healthy weight” correctly identified their child. However, for preschoolers in the overweight category, none identified their preschooler as “too heavy” and only 22% of mothers correctly identified their preschooler as “too heavy” when the child's weight status was obese. Finally, 43% of mothers correctly identified their preschooler as being underweight. Results show that while mothers may accurately identify preschoolers who are at a healthy weight, they incorrectly report weight status for those defined as overweight, obese, and underweight. Funded in part by USDA FNS.
Qualitative Assessment of Resources Needed by Third and Fourth Year Medical Students for the Prevention and Treatment of Childhood Obesity
Authors: Raad Alice A. , Cooke Natalie K. , Alexander De'Ja S. , Lang Brittany A. , Wheeley Jennifer R. , Goodell L. Suzanne
Published: June 2021

Healthcare providers should to be equipped with the necessary information, resources, and skills to treat and prevent childhood obesity. This qualitative assessment focused on medical students’ understanding of childhood obesity and what they believe is lacking from their training to treat and prevent childhood obesity. Individual interviews were conducted with both allopathic and osteopathic third and fourth year students throughout the United States. Researchers found that students felt inadequate in preventing and treating childhood obesity. Students said that they would benefit if referred to the proper information from clinical studies they could share with patients, community educational programs in which to refer their patients, and nutritional pamphlets to send home with their patients. Some students stated a need for skills to interact with both children and their parents, and students want to learn motivational interviewing skills to encourage and promote healthier lifestyles. Some students said that they would benefit from lectures on childhood obesity and the basics of nutrition. Medical students want to be more prepared to work with obese patients and would like to receive resources to be successful physicians in addition to the extensive medical knowledge they are already receiving. With the proper nutrition education, healthcare providers may feel confident in working with obese children.

Grant Funding Source : N/A
An Ecological study on food consumption patterns and childhood obesity in schools
Authors: Cuevas-Nasu Lucia , Shamah-Levy Teresa , Méndez-Gómez-Humarán Ignacio , Méndez-Ramírez Ignacio
Published: June 2021

Objective

Evaluate the association between food consumption with overweight and obesity (OW+O), in a representative sample of school children in Mexico.

Methods

We assessed nutriment consumption (energy, carbohydrates, lipids, fiber and sodium) in 8,367 children with food and beverages consumption records during journey from home to school and back (out of home=OH), and global consumption (GC). We standardized average consumption by state. Ward clustering method was used to group consumption patterns. Analysis of variance was used for evaluate consumption patterns association with OW+O.

Results

We selected 4 consumption groups: 1) all nutrients at average in OH and slightly lower in GC; 2) all nutrients high OH and high in all nutrients in GC but low in fiber; 3) all the nutrients were slightly lower OH and in average in GC; and 4) all the nutrients were low OH and all the nutrients in GC, but high in fiber. Tukey‐Kramer test shows a significant higher prevalence of OW+O in cluster 2 with respect to cluster 4.

Conclusion

Higher nutrient consumption OH and GC, with low fiber is associated with higher prevalence of OW+O.
A Conceptual Model Elucidating the Relationships between Television and Childhood Health Outcomes
Authors: Berhaupt-Glickstein Amanda , Martin-Biggers Jennifer , Worobey John , Byrd-Bredbenner Carol
Published: June 2021

The IOM's L.E.A.D. framework (Locate, Evaluate, and Assemble evidence to inform Decisions) guided a comprehensive analysis of research examining links between TV (amount, content) and child health outcomes, which resulted in the development of a novel conceptual model expressing these links and strengths of relationships. Terms searched in CINAHL, PubMed, and PsychInfo databases (children, food marketing, BMI, television, media) yielded 39 articles. Research suggests links between TV usage and physical health (BMI, eating disorders, hypercholesterolemia, hypertension, asthma, sleep disorders), psychological health (depression, mood disorders), behavior (violence, aggression, substance abuse), and learning. TV's contribution to BMI include calorie conservation via displacement of energy expending activities and increased energy intake by promoting more eating occasions featuring calorie‐dense foods. Interventions aiming to reduce TV viewing and children's BMI have mixed results indicating a need to help parents understand TV's role in children's health and the importance of establishing household policies regulating TV viewing time. This study's conceptual model can be used by health promotion and nutrition communication professionals to visually convey to parents the health consequences of TV viewing to increase their understanding of how TV affects child health.
Summer camp promotes anthropometric changes in overweight youth in Fresno, California
Authors: George Gretchen , Schneider Constance , Ginsburg David , Kaiser Lucia
Published: June 2021

The purpose of this study was to examine the effect of a nutrition‐themed camp on cardiovascular risk factors in low‐income overweight and obese youth (body mass index for age, BMI > 85th percentile). During summer 2011, 96 youth, ages 9–17 yrs, participated in the Fresno Parks and Recreation Fitness Camp (FC). The five week camp included 2–3 hours of physical activity daily and nutrition education, taught by the University of California CalFresh Nutrition Education Program. A control group (n=15 youth) from the camp waitlist was followed for the same period without exposure to FC. Trained staff measured weight, height, and waist circumference and collected 24 hour diet recalls from the youth at baseline and end of camp. Using analysis of variance, significant differences were observed in pre‐post weight change between FC (−1.06 kg in 9–11 yr olds and −1.58 kg in 12–17 yr olds) and controls (+0.33 kg), after controlling for baseline BMI z‐score (p=0.04). Waist circumference change was also significantly different among FC and controls after controlling for baseline BMI z‐score (p=0.003). Nutrition‐themed summer camps may play a role in reducing excess body weight and waist circumference in low‐income youth. Funded in part by University of California CalFresh Nutrition Education Program (formerly known as UC FSNEP)
Contribution of total and central adiposity to systemic adipokines during weight loss
Authors: Gletsu-Miller Nana , Lin Edward
Published: June 2021

Total and central adiposity is linked with disease risk through the activation of inflammatory pathways, but the contribution of fat depots to systemic concentrations of pro‐ and anti‐inflammatory cytokines is unclear. Objectives were to determine associations among measures of total (TAT), abdominal visceral (VAT) and subcutaneous adipose tissue (SAT), and plasma concentrations of leptin, C‐reactive protein (CRP), and adiponectin in severely‐obese women (N = 48) during weight loss for 6 months following gastric bypass surgery. TAT was assessed using air‐displacement plethysmography; VAT and SAT using computed tomography; cytokines using enzyme‐linked immunoassay. Body mass index decreased from baseline to 6 months (46.3±0.7, 34.8±0.7kg/m2), primarily due to decreases in TAT (69.7±1.8, 42.7±1.5kg), VAT (4,160±240, 2,510±180cm3) and SAT (14,320±500, 9,280±390cm3) (all P<0.05). Plasma concentrations of CRP (1.29±0.13, 0.58±0.08mg/dL) and leptin (134.7±9.2, 49.0ng/mL) decreased, and adiponectin increased (6.10±0.5, 8.04±0.7ng/L). At baseline and at 6 months following weight loss, there were strong correlations between CRP and TAT (r = 0.36 and 0.38, respectively), and SAT (r = 0.46 and 0.42) but not VAT. For leptin, correlations were observed with TAT only, at both timepoints (r = 0.48 and 0.87). For adiponectin, negative correlations were observed with TAT and SAT (r = −0.42 and −0.46) but not VAT, at 6 months. No longitudinal relationships were found between adipose tissue and cytokine concentrations. In conclusion, TAT and abdominal SAT were more strongly associated with systemic CRP, leptin, and adiponectin concentrations compared to VAT. Future studies should clarify the contribution of regional versus total adiposity to systemic inflammation.
The abundance of the mRNA translation initiation inhibitor PDCD4 in L6 myotubes is regulated by mTORC1 and the proteasome
Authors: Adegoke Olasunkanmi John , Kakade Dhanshri Michelle , Islam Nushaba
Published: June 2021

The mammalian target of rapamycin complex 1/ S6 kinase 1 (mTORC1/S6K1) pathway is a critical regulator of muscle protein synthesis and mass. Using L6 myotubes, we characterized the regulation of the mRNA translation inhibitor programmed cell death 4 (PDCD4), a recently described substrate of the mTORCI/S6K1 pathway. Myotubes were cultured in amino acid‐free, serum‐free medium for 12 h, and then refed for 1 or 3 h. Starvation decreased the phosphorylation of S6K1, the PDCD4 kinase (P<0.01). Starvation increased the abundance, but not the phosphorylation, of PDCD4 >4 fold (P<0.001); refeeding reversed the effects of starvation on S6K1 and PDCD4. Rapamycin or MG132 (an inhibitor of the proteasome) prevented the refeeding‐associated decrease in PDCD4 abundance. Because PDCD4 inhibits translation by binding to the eukaryotic initiation factor 4A (eIF4A), we assessed this interaction. Starvation increased the % of PDCD4 bound to eIF4A (P<0.05); this was reversed during refeeding. Rapamycin prevented the effect of refeeding. Thus, we showed that in skeletal muscle cells, the abundance of PDCD4 and its interaction with the initiation factor eIF4A were reversibly modified by nutrients, and that the activities of mTORC1 and of the ubiquitin dependent proteolytic system were required for this regulation. Manipulation of PDCD4 abundance may offer an approach to stimulate mass. Funded by NSERC.
Fasting and refeeding regulate in different manner SNAT 2, SREBP‐1 and 2, mTOR, serum insulin in animals fed different types of protein
Authors: Ortiz-Huidrobo Rosa Isela , Marquez-Mota Claudia , Quiñonez-Peña Alejandra , Tovar-Lopez Eduardo , Galvez-Mariscal Amanda , Tovar Armando R , Torres Nimbe
Published: June 2021

Several transcriptional factors or receptors have been described as sensors of carbohydrates or fatty acids to regulate the utiization of these nutrients, however there is scarce information about the sensors for amino acids. Thus, the purpose of the present work was to assess whether different types of proteins regulate serum insulin, mTOR, SNAT2, SREBP1 and SREBP2 during fasting and refeeding. Male Sprague Dawley rats were fed 20% protein diets: casein (C) soy (SY), corn gluten (G), sesame (SE), green pea (GP), black bean (BB), black bean plus corn gluten and spirulina (S) for 21 days. Rats fed with G, SE or S gained less weight that the rest of the groups. mTOR mRNA expression correlated with the amount of leucine in the diet (P<0.01). Serum Insulin, and SREBP‐ 1 and FAS showed the lowest expresion during fasting and the highest expression after 1h refeeding. SNAT 2 was repressed after refeeding and was stimulated mainly by soy and GP, and SREBP‐2 decreased in the refeeding. Thus, fasting, refeeding and protein quality regulate in different extent these genes. Supported by IcyT DF (AG).
Partially hydrolyzed soy protein shows enhanced transport of amino acids compared to nonhydrolyzed protein across an intestinal epithelial cell monolayer
Authors: McGraw Nancy Jean , Napawan Nida , Toland Mitch , Schulze John , Tulk Barry , Krul Elaine
Published: June 2021

Consumption of protein hydrolysates has been proposed to stimulate muscle protein anabolism to a higher degree than intact (nonhydrolyzed) proteins due to their ability to more effectively provide amino acids for muscle protein synthesis (MPS). Our objective was to evaluate whether amino acid uptake & transport to the basolateral surface of intestinal Caco‐2 cells was enhanced for soy protein hydrolysates compared to nonhydrolyzed soy protein. Intact & partially hydrolyzed soy proteins were subject to simulated gut digestion using pepsin & pancreatin. The resultant soluble peptide fractions (7 mg/mL) were applied to the apical surface of Caco‐2 monolayers (n = 4 to 6 per treatment) & incubated for 3 hours. Volume from each basolateral chamber was harvested, lyophilized & quantitatively analyzed for free amino acids using ion‐exchange chromatography & comparison to an included reference standard. Concentrations of all amino acids in the basolateral media were higher by a mean of 44% (p = 0.019) for hydrolyzed soy protein compared to that from the nonhydrolyzed protein with Asx, Glx & Lys showing the greatest differences. These data support the hypothesis that intestinal absorption of hydrolyzed soy protein may result in a more rapid absorption & increased availability of dietary amino acids. This would be important in conditions where rapid & increased levels of amino acids are needed such as in the stimulation of MPS.
In vivo postprandial lipid partitioning in liver and muscle of diabetic rats is disturbed
Authors: Prompers Jeanine J , Jonkers Richard AM , van Loon Luc JC , Nicolay Klaas
Published: June 2021

Objective

To study in vivo lipid partitioning in insulin‐resistant liver and muscle of diabetic rats using magnetic resonance spectroscopy (MRS).

Methods

Four groups of n=6 male Zucker diabetic fatty rats were used for this study: obese, pre‐diabetic fa/fa rats and lean, non‐diabetic fa/+ littermates at the age of 6 weeks, and obese, diabetic fa/fa rats and lean, non‐diabetic fa/+ littermates at the age of 12 weeks. 1H‐[13C] MRS measurements were performed in liver and tibialis anterior muscle at baseline and 4, 24 and 48 h after oral administration of 1.5 g [U‐13C] Algal lipid mixture per kg body weight.

Results

At baseline, total lipid content was higher in fa/fa rats compared with fa/+ rats in both liver and muscle, and at both ages. Both in pre‐diabetic and in diabetic fa/fa rats, hepatic lipid uptake was increased compared with non‐diabetic fa/+ rats. Likewise, in muscle of diabetic fa/fa rats, lipid uptake was higher than in muscle of fa/+ rats. In contrast, lipid uptake in muscle of younger, pre‐diabetic fa/fa rats was lower than in controls.

Conclusion

In the pre‐diabetic state, muscle appeared to be protected from massive lipid uptake, whereas lipid uptake in the liver was largely increased. In contrast, after developing full‐blown diabetes, lipid uptake was highly elevated in both liver and muscle. This research was funded by a VIDI grant from the Netherlands Organisation for Scientific Research (NWO).
Effects of 12 types of oils from plant seeds on lipid metabolism of mice
Authors: Choi Kyung Soon , Chung Keun Hee , Shin Kyung Ok , Huh Seon Min , Kim Sun Ok , Kim Yong Hwan
Published: June 2021

Mice were fed 12 types of dietary oils from plant seeds in order to study their effects on lipid metabolism. Cholesterol level was 202.40±44.08 mg/dl (highest) in mice fed gorosoe seeds, and it decreased in mice fed loofah seeds, magnolia seeds, and Taxus cuspidata S. et Z. (p<0.05).

HDL‐C level in mice fed gorosoe seeds was 175.80±27.66 mg/dl, LDL‐C level was 23.60±17.47 mg/dl, and TG level was 257.00±48.18 mg/dl. All of these levels were higher than those in mice fed other types of oils. Saturated fatty acid level in mice fed gorosoe seeds was 3.395%, whereas that in mice fed Chionanthus retusus lindl. & paxton seeds was the highest.

Liver weight of mice fed cherry blossom seeds and Chionanthus retusus lindl. & paxton seeds was the highest, and pancreas weight of mice fed cherry blossom seeds was the highest (p<0.05). Further, kidney weight of mice fed acacia seeds was the highest. Fat levels of internal organs of mice fed loofah seeds were the highest (p<0.05). Further, body weights of mice fed loofah seeds, gorosoe seeds, and magnolia seeds were generally higher.

Therefore, the study of dietary plant oils as an alternative energy source should be continued.

Grant Funding Source : Sahmyook University
Practical Utility of Lipid Predictive Equations in a Diabetic Population
Authors: Horton Sarah E , Sauder Katherine A , Kris-Etherton Penny M , West Sheila G
Published: June 2021

In the 1960s, Ancel Keys created an equation to predict how total blood cholesterol levels are affected by dietary modification. This equation has since been modified and applied to triglycerides, LDL, and HDL cholesterol. We assessed the practical utility of 11 published equations in Type 2 diabetics using self‐reported dietary data. In a larger clinical trial, 21 participants completed three daily food logs followed by a two‐week controlled feeding period. Fasting lipid profiles were assessed prior to study entry and after completion of the study diet. The difference between the participants’ personal diets and the study diet was used to predict lipid changes between the eating periods. The predicted lipid changes were compared to the observed lipid changes using a correlation analysis. For total cholesterol, the Original Keys Equation yielded the only predicted change that was significantly correlated with the observed change (r=0.45, p=0.04). For HDL cholesterol, the Yu equation yielded the only predicted change that was significantly correlated with the observed change (r=0.47, p=0.03). The predicted changes in LDL cholesterol and triglycerides were not correlated with the observed changes. Our findings demonstrate that for self‐reported dietary data, the Original Keys Equation provides the best estimate of total cholesterol changes in a diabetic population.

Funding: American Pistachio Growers
Quantitative Analysis of Trans‐Fatty Acids in Human Plasma
Authors: Kuiper Heather C , Meyers Tunde , Ribera Ashley M , Muresan Marcela C , Smith Antoinette R , Waters Christina W , Vesper Hubert W
Published: June 2021

Trans‐fatty acids (TFA) intake has been associated with risk factors for cardiovascular disease. However, little is known about the TFA levels in humans or about how these levels relate to other fatty acids (FA).

In order to assess TFA levels in humans we have developed and validated an isotope dilution‐gas chromatography‐negative chemical ionization‐mass spectrometry method for the quantitation of 28 FA in human plasma, including 4 major TFA. We analyzed 73 convenience samples from adults. All samples contained TFA, with average levels ± standard deviation of 2.66 ± 1.29 μM for palmitelaidic acid 12.70 ± 8.31 μM for elaidic acid, 16.59 ± 11.10 μM for vaccenic acid, and 1.15 ± 0.52 μM for linoelaidic acid. The sum of all FA was 9647 ± 2913 μM. The sum of the 4 TFA accounted for 0.34 ± 0.20 % of total FA. FA values expressed as percent of total FA showed negative association between monounsaturated FA and polyunsaturated fatty acids (PUFAs), ω‐6 PUFAs, and ω‐3 PUFAs. Negative trends were also seen between certain TFA and the summed PUFAs. We have developed an analytical method that enables the assessment of major TFA and other FA in 100 μL of plasma, which allows the investigation of FA concentrations as well as differences in the composition of these FA in plasma. This method is being used to analyze samples from the National Health and Nutrition Examination Survey (NHANES).
Effect of docosahexaenoic acid (DHA) ingestion on muscle damage response to resistance exercise and training
Authors: Rankin Janet Walberg , DiLorenzo Frank M. , Drager Christopher J.
Published: June 2021

Muscle damage and soreness may discourage resistance exercise participation. Our purpose was to determine if DHA ingestion affects the muscle damage response to: 1. acute eccentric exercise, 2. initiation of a subsequent resistance training program. Forty‐one healthy, untrained young adult male subjects consumed DHA (2 g/d) or placebo for 28 d before an eccentric exercise bout with the non‐dominant arm (six sets of 10 using 140% 1RM) on day 1. Subjects continued supplementation and began a multiple‐exercise resistance training program on day 4 and continued 3 d per week through d 17. Muscle damage was assessed using maximal isometric muscle force, delayed onset muscle soreness (DOMS, 100 mm scale), range of motion (ROM) and serum CK (analyzed as log) on days 1, 2, 3, 4, 7, 12, 17. The acute response to eccentric exercise (day 1–4) was reduced muscle strength (32.9%) and ROM (16%) and increased DOMS (32 mm) and CK to 3713 U/L. DHA lowered the overall CK response (p= 0.045) but did not influence the response of other factors to the acute bout. When all time points were analyzed, DHA did not influence muscle strength or ROM response but tended to dampen CK (p = 0.058) and DOMS (p = 0.086) over the 17 days. In summary, DHA reduced a marker of muscle damage following acute eccentric exercise and tended to dampen this marker and soreness during the initial period of resistance training. Funded by a grant from Martek Biosciences Corporation.
Docosahexaenoic acid regulates 5′ AMP‐activated protein kinase in adipocytes
Authors: Huang Chao-Wei , Chen Yu Jen , Lin Yuan-Yu , Mersmann Harry John , Ding Shih-Torng
Published: June 2021

Docosahexaenoic acid (DHA) promotes lipolysis in animal livers and decreases the incidence of metabolic syndrome in human. Feeding weaning pigs diets with 2% soybean oil, beef tallow or DHA oil for 1 month to measure the effect of dietary oils on body weight and gene expression related to lipid metabolism, we found pig body weights were not affected by different dietary treatments, but the triglyceride concentration in plasma was reduced by the DHA treatment. The protein level of 5′ AMP‐activated protein kinase (AMPK) was significant decreased by the DHA treatment when compared to the beef tallow treatment (p <0.05). However, the hormone sensitive lipase (HSL), a lipolytic enzyme and phosphoenolypyruvate carboxykinase (PEPCK), an enzyme for glyceroneogenesis, were not affected by dietary oils. To investigate the acute effect of DHA on the expression of genes related to lipid, we induced preadipocyte 3T3‐L1 to adipocytes, and treated with or without 100 μM DHA for 15, 30 and 60 min. The gene expression of peroxisome proliferator activated receptor γ (PPARγ), adiponectin, adiponectin receptor 1, AMPK and PEPCK was not affected by the DHA treatment. Fatty acid synthase (FAS) was significantly increased (p <0.05). The data suggest that DHA may increase the expression of AMPK to affect its downstream gene function in order to midify cellular physiology. This observation gives a good hint to study whether DHA can affect cellular function through AMPK pathway.

Grant Funding Source : National Scince Council
EPA decreases mRNA and protein for endocannabinoid receptors in myoblasts
Authors: Kim Jeffrey , Li Yong , Watkins Bruce A
Published: June 2021

Our research objective is to characterize the actions of n‐3 PUFA on mRNA and protein levels for endocannabinoid (EC) receptors (CB1 and CB2) and the EC synthesizing and degrading enzymes in muscle. In two experiments, C2C12 myoblasts were cultured until 50% confluency. Cells were assigned to two groups: one maintained with standard growth media (proliferating) and the other with differentiating media (differentiated). After 48 h, both groups were treated with 100μM of either eicosapenaenoic (EPA), docosahexaenoic (DHA) and arachidonic acids (AA), or bovine serum albumin (BSA) control for 24 h. RNA was then isolated from cells and subjected to real time PCR analysis. Compared to the BSA, the amount of CB2 in EPA and DHA treated cells was lower in differentiated cells. The EPA treated proliferating cells had lower CB1 and CB2 compared to the AA and BSA control. CB1 protein was lower in differentiated cells treated with EPA. The synthesizing enzymes, NAPE‐PLD and DAGL, of the endogenous cannabinoids anandamide (AEA) and 2‐ arachidonylgycerol (2‐AG); respectively, mRNA was lower in differentiated cell treated with DHA and EPA. These data suggest that DHA and EPA may potentially inhibit EC signaling in C2C12 by reducing the agonists (AEA and 2‐AG) and their receptors. Thus treatment of myoblasts with DHA or EPA results in lower mRNA for EC receptors and endogenous cannabinoid synthesizing enzymes in proliferating C2C12.

Grant Funding Source : Diet and Health Initiative (UConn)
Variability of Oxidant Status in Women of Childbearing Potential
Authors: Artz Tamara , Jalili Thunder , Goodman Michael , Murtaugh Maureen A
Published: June 2021

Objective

Oxidant status may influence conception after in vitro fertilization, maternal health during pregnancy, and fetal outcomes including birthweight. However, few reports exist of oxidant status in women of childbearing potential. Therefore, we describe the range of oxidant status in a group of potentially fertile women (n=96).

Methods

We conducted a cross‐sectional study of dietary supplement intake and blood and urine biomarkers of oxidative status (serum total glutathione (TGLUT) Oxis Research and urinary 8‐isoprostane (8‐ISO) Cayman Chemical Co. Statistics were run using SAS version 9.2 using log transformed variables where appropriate.

Results

Women averaged 31 years (range 18 – 49, sd=8.5) with up to 4 live births. Sixty‐one women reported using any supplement, 23 used multivitamins and 11 prenatal vitamins. TGLUT varied four fold (mean=818.0 uM, 95%CI=201.5–1907.8). Urine 8‐ISO varied 80‐fold (mean=115.0 pg/mL, 95%CI=4.5–458.5T). TGLUT and 8‐ISO were positively correlated (r=0.24, p<0.02). TGLUT was higher among women using vitamin C, vitamin E, lutein, lycopene, carotenoids (p=0.03) vs. non‐users.

Conclusions

The positive correlation of vitamin C supplementation with total glutathione concentrations suggests that vitamin C may be an effective strategy for augmenting plasma glutathione in women of childbearing potential.
Development of an outpatient biotin feeding protocol for studies of biotin requirements in adults
Authors: Eng Wei Kay , Giraud David W , Schlegel Vicki L , Wang Dong , Zempleni Janos
Published: June 2021

Human biotin requirements are unknown. Previous studies of biotin metabolism at physiologically relevant levels, ranging from moderate deficiency to moderate excess, required costly inpatient settings. We sought to develop a cost‐efficient outpatient protocol based on feeding egg white shakes. In this protocol, subjects are required to consume an egg white shake with every major meal. The avidin protein in spray‐dried egg white binds biotin and prevents its absorption, i.e., egg white can be used to titrate the amount of available biotin in the diet. The following three levels of biotin supply were tested. (a) Deficiency = sufficient egg white to saturate all the biotin in a typical American diet. (b) Control = biotin‐saturated egg white plus 30 μg biotin/d. (c) Supplemented = biotin‐saturated avidin plus 600 μg biotin/d. As of today, 11 adults have completed the study. The abundance of biotinylated carboxylases and the urinary excretion of biotin (0.26±0.15 vs 0.35±0.15 vs 3.2±0.67 nmol biotin/μmol creatinine) depended on the amount of free biotin in test diets, suggesting efficacy of treatment. We conclude that the new outpatient protocol is an effective and cost‐efficient alternative to costly in‐patient protocols. (UNL ARD Hatch Act, NIH DK063945, DK077816, and DK082476)