bluuebunny/crossref_metadata_2025 huggingface dataset:
Estrogen and progesterone do not mediate the attenuated febrile response to E. coli LPS in rats near the term of pregnancy
Authors: Finley Caitlin R , Fewell James E.
Published: June 2021

The febrile response to LPS is attenuated in rats near the term of pregnancy at a time when plasma concentrations of estrogen (E) and progesterone (P) are elevated. In an attempt to clarify mechanisms, the present experiments were carried out on chronically‐instrumented, conscious rats to test the hypothesis that elevated plasma concentrations of E and P similar to that observed near the term of pregnancy would attenuate the febrile response to LPS in non pregnant rats (NP). NP and oophorectimized rats received intraperitoneal vehicle (V) or E, P, E+P over 3.5 days in amounts sufficient to produce plasma concentrations observed near the term of pregnancy. Core temperature was recorded via radio telemetry. Hormone treatment did not alter basal core temperatures nor the core temperature responses to an EC50 dose of E. coli LPS. Thus, our data do not support the hypothesis that elevated plasma concentrations of E & P mediate the attenuated core temperature responses to LPS in rats near the term of pregnancy.
Protective effects of loading combined with astaxanthin on capillary regression of disused muscle
Authors: Kanazashi Miho , Tanaka Minoru , Tanaka Masayuki , Kondo Hiroyo , Murakami Shinichiro , Fujita Naoto , Fujino Hidemi
Published: June 2021

PURPOSE

Disuse‐induced muscle atrophy and capillary regression in skeletal muscle are related to overexpression of oxidative stress caused mitochondrial dysfunction. The purpose of the present study was to identify the effect of loading combined with astaxanthin on capillary regression of the soleus muscle induced by hindlimb unloading.

METHODS

Thirty‐five adult male rats were divided into control, hindlimb unloading (HU), HU+astaxanthin (Ax), HU+loading (Lo) and HU+Ax+Lo groups.

RESULTS

HU resulted in a decreased muscle mass and capillary regression. The loading attenuated the muscle atrophy, which increased the ROS and SOD‐1, resulting in a capillary regression. The combination of loading and astaxanthin attenuated the overexpression of oxidative stress. In addition, the combination increased the expression of e‐NOS, PGC‐1α and succinate dehydrogenase activity, reflecting a protective effect of mitochondrial function and the architecture of capillary network.

CONCLUSION

Loading combined with astaxanthin is effective in preventing capillary regression in the soleus muscle induced by hindlimb unloading. Supported by Grants‐in‐Aid for Science Research from the Japanese Ministry of Education, Culture, Sports, Science and Technology.
Absence of reproductive organs increases somatic maintenance in the Hawk moth, Manduca sexta
Authors: Ojha Jaika , Davidowitz Goggy
Published: June 2021

Flight and reproduction are major resource sinks in flying organisms. Theory predicts that reducing reproduction allows more nutrients to be allocated for maintenance of somatic tissues, such as flight muscles. We tested this hypothesis by comparing the flight muscle structures of oophorectomized (ovaries removed) and orchiectomized (testes removed) individuals at different ages in Manduca sexta. Overall, oophorectomized and orchiectomized individuals have significantly greater number of mitochondria and percentage of area occupied by mitochondria compared to sham‐operated individuals. In addition, oophorectomized and orchiectomized individuals have significantly longer sarcomeres and larger size myofibrils compared to sham‐operated individuals. At day 7, oophorectomized and orchiectomized individuals exhibited smaller size mitochondria compared to sham‐operated individuals, suggesting a delay in mitochondrial degeneration. The levels of glycogen granules at different ages were also higher in oophorectomized and orchiectomized individuals compared to sham operated individuals. There was also a positive relationship between duration of flight and number of flight muscle mitochondria. These findings directly suggest that in the absence of reproductive organs, the increase in available energy is utilized for the maintenance of flight muscles.
Caveolin‐1's role on the neuromuscular junction of αC418W SCCMS mice
Authors: Yan June Kalay , Reyes Jose Gabriel Grajales , Quesada Orestes , Dominicci Jose Lasalde
Published: June 2021

Slow Channel Congenital Myasthenic Syndrome (SCCMS) is an inherited genetic disorder caused by mutations in the muscle nicotinic acetylcholine receptors (nAChRs) affecting the neuromuscular transmission. Despite the extensive research performed, this disease still challenges many patients by causing muscle weakness, fatigue, and even death in severe cases. To further characterize this disease, we used transgenic mice models to study the role of caveolin‐1 protein and its relationship with nAChRs expressing the αC418W, a SCCMS‐causing mutation. This mutation shows a caveolin‐1 binding motif that arrests the nAChR in lipid rafts. To study this relationship, we silenced the expression of caveolin‐1 in the muscle endplate by RNA interference and performed immunohistochemistry experiments on the Tibialis anterior (TA) muscle to observe the colocalization of caveolin‐1 and the acetylcholine receptors. We were able to knock down the expression of caveolin‐1 by transfecting the TA muscle with three different shRNA clones through electroporation, clone 2 being the most efficient. These results would allow us to determine the role of caveolin‐1 in the synaptic transmission of transgenic mice expressing the αC418W mutation through electrophysiological studies. Ultimately, this would provide us with better understanding of this rare neurodegenerative disease in efforts of improving current treatments and elucidating new approaches. Work supported by “URM: Mentoring Program in Neural Circuits and Behavior at the University of Puerto Rico”, Award No. DBI‐0932955.
Localization of a Novel Renal Olfactory Receptor to Glomeruli
Authors: Aisenberg William , Pluznick Jennifer
Published: June 2021

Olfactory receptors (ORs) are chemosensory G Protein Coupled Receptors that comprise the largest mammalian gene family. ORs serve to identify odors in the nose, and also act as chemosensors in a variety of other tissues. We previously identified 8 renal ORs; here, we undertook a directed RT‐PCR screen for 10 ORs (primers were validated using genomic DNA, taking advantage of the fact that ORs lack introns). We identified 4 murine renal ORs consistently present in multiple kidney samples: Olfactory Receptors 31, 746, 1418 and 1426 (Olfr31, Olfr746, Olfr1418, and Olfr1426; sequenced to confirm). Among these, only Olfr31 has a clear human ortholog. No validated antibodies are available for these ORs. Therefore, to localize these ORs we developed a laser capture microdissection protocol for specific kidney segments, followed by RNA isolation and RT‐PCR. Olfr31 localized to glomeruli by RT‐PCR (glomeruli RNA sample purity was validated by RT‐PCR for nephrin, and absence of RT‐PCR band for NCC and megalin). We have now cloned the full‐length sequence of Olfr31, and hope to identify its ligand(s) using a reporter gene assay (Olfr31 has no known ligand). In sum, we have identified four murine renal ORs and have localized one, Olfr31, to renal glomeruli. Further studies will focus on localizing Olfr746, Olfr1418, and Olfr1426; identifying Olfr31 ligands, and examining the potential roles of these receptors in vivo. Funding: NIDDK
Using the T2DN rat as a model to determine therapeutic efficacy of Serelaxin (recombinant human relaxin‐2) for Diabetic Nephropathy
Authors: Gillis Ellen , Mooney Jennifer , Roman Richard J. , Williams Jan M. , Sasser Jennifer M.
Published: June 2021

Recent studies demonstrate renoprotective and antifibrotic effects of relaxin in non‐diabetic kidney disease. To test the hypothesis that relaxin protects against diabetic renal injury, we infused Serelaxin (RLX, 4ug/h, Corthera, s.c. minipump) or vehicle into 10–12 month old male T2DN rats for 3 weeks (n=10/group). An ELISA confirmed delivery of RLX (21±2 ng/mL plasma, nondetectable in control). Baseline protein excretion (142±27 vs 144±39 mg/d) and blood glucose (322±32 vs 296±31 mg/dL) were similar in RLX and untreated T2DN, respectively. After treatment, RLX and control groups showed no significant differences in blood glucose (313±18 vs 288±23 mg/dL), MAP (130±8 vs 118±7 mmHg), or proteinuria (212±48 vs 199±63 mg/d). Masson's trichrome staining of kidney sections revealed significant glomerular and tubulointerstitial injury in both groups, with no remarkable changes following RLX treatment. There were no differences between the RLX and control groups (n=5) in renal blood flow (6.0±1.7 vs 6.9±2.6 mL/min) or glomerular filtration rate (3.2±1.3 vs 3.3±1.2 mL/min). We conclude that the T2DN rat is a suitable model for diabetic nephropathy as it does exhibit progressive proteinuria and renal injury similar to human diabetic nephropathy; however, 3 weeks of RLX treatment is not sufficient to reverse established renal injury present in the T2DN rat. Earlier and/or longer treatment with RLX may be required.
Effects of microgravity on immune function: benzofuran‐2‐carboxylic acid derivative as a countermeasure (1010.14)
Authors: Osborne Amanda , Agee Joshua , Scott Ansley , Shenwu Ming , Sundaresan Alamelu , Marriott Karla , Bhuiyan Shakhawat , Wilkins Richard , Gersey Brad , Denkins Pamela , Williams Willie , Mao Jinghe
Published: June 2021

Microgravity, or zero gravity, suppresses immune function and threatens the health of those exposed to it. Astronauts are especially exposed to microgravity during spaceflight. With more and longer voyages through outer space occurring, it is imperative to develop countermeasures to prevent these effects. These countermeasures include a Benzofuran‐2‐carboxylic acid derivative, KMEG. Initial findings suggest KMEG increases cell proliferation and immune function. The hypothesis states: KMEG treated macrophages exposed to simulated microgravity will show an increase in immune function compared to those not treated and exposed to simulated microgravity. A bioreactor was used to simulate microgravity for at least 48 hours. The genes involved in the Stress & Toxicity PathwayFinder were examined using RT2 ProfilerTM PCR Array. Compared to non‐treated macrophages, the gene expression profiles showed a decrease in the expression of DNA damaging and repair genes and oxidative stress genes of the KMEG treated macrophages. Inflammation genes were more expressed in KMEG treated macrophages. The apoptosis signaling gene was down‐regulated in KMEG treated macrophages, while it was up‐regulated in non‐treated macrophages. Therefore, KMEG could help alleviate the immune system suppression caused by microgravity.

Grant Funding Source: Supported by ISS Project (UR) 1 (NNX13AK89A) and NASA EPSCoR (NNX12AK85A)
Effects of tributyltin exposures on secretion of interleukin 1 beta from human immune cells (1012.1)
Authors: Brown Shyretha , Whalen Margaret
Published: June 2021

Tributyltin (TBT) is an organotin compound used as a biocide in a variety of industrial applications such as wood preservation and as an antifungal. It has been found in human blood samples. Interleukin 1 beta (IL‐1β) is produced by monocytes and macrophages and promotes cell growth, tissue repair, and regulates immune response. IL‐1β appears to increase the invasiveness of certain tumors. The aim of the current study is to determine if exposures to TBT modify secretion of IL‐1β from increasingly reconstituted preparations of human immune cells. TBT concentrations of 25 to 200 nM at 24h, 48h, or 6 days were examined in highly enriched human NK cells, monocyte‐depleted human peripheral blood mononuclear cells (PBMCs), PBMCs, granulocytes, and a combination of PBMCs and granulocytes. IL‐1β was measured using an enzyme‐linked immunosorbent assay (ELISA). Results show TBT alters IL‐1β secretion from all cells preparations. 200 nM concentrations of TBT blocked the secretion of IL‐1β, while lower concentrations of TBT elevated secretion of IL‐1β. Concentrations and lengths of exposure to TBT that caused statistically significant increases in IL‐1β secretion from human immune cells varied from one donor to the next. The data indicates that TBT‐induced alterations of IL‐1β secretion from immune cells may be a significant consequence of TBT exposures that may potentially affect immune competence and cancer invasiveness.

Grant Funding Source: Supported by NIH grant 5U54CA163066‐02
Nutrition education for medical students: 4th year transition to residency for primary care (1020.3)
Authors: Edwards Marilyn
Published: June 2021

Nutrition Education for Medical Students: 4th Year Transition to Residency for Primary Care

Marilyn S. Edwards, Ph.D., R.D., Department of Internal Medicine, University of Texas Medical School, Houston, TX 77030

Objectives: 1. To provide medical students the skills for counseling patients on effective diet and lifestyle modification for obesity, diabetes, hypertension, and cardiovascular disease.

2. To develop competency in the assessment of physical activity and writing a prescription for appropriate exercise for patients.

3. To develop skills to initiate a physician referral for Medical Nutrition Therapy.

Methods: Participants in a 2‐hour Transition to Residency Nutrition Workshop use the interactive web‐based Nutrition in Medicine (NIM) short courses to develop clinical skills for assessing and counseling patients. Students begin with the 5 Stages of Change for patient counseling and develop specific skills relevant to patients with obesity, diabetes, hypertension, and cardiovascular disease. Students assess whether patients meet physical activity guidelines, address barriers, and write a prescription for physical activity. The workshop concludes with students developing skills to initiate a physician referral for Medical Nutrition Therapy including diagnosis code, relevant medications and lab values.

Results: Evaluations from 4th year medical students indicate that a hands‐on interactive workshop reinforces their nutrition knowledge and clinical skills relevant to chronic disease and is essential in preparing for residency programs in internal medicine, family medicine, and ob/gyn.

Conclusions: Given the limited curriculum time devoted to teaching nutrition to medical students, a critical time in the training of physicians comes just prior to starting a residency program. At the University of Texas Medical School at Houston, an opportunity is provided for students to reinforce their clinical nutrition skills and to successfully counsel patients.
Prevalence of orthorexia nervosa among students at a rural university (1021.10)
Authors: Neyman Morris Michelle , Clark Courtney , Silliman Kathryn
Published: June 2021

Orthorexia Nervosa (ON) is characterized by an obsession with healthy eating which when taken to the extreme may lead to severe weight loss, nutrient deficiencies and social isolation. The objective of this study was to determine the prevalence of ON tendencies among a sample of college students at a rural northern California university. A convenience sample of 448 male (n=95, 21%) and female (n=353, 79%) students from California State University, Chico completed an online survey which included demographic and lifestyle behavior questions, and the ORTO‐15, an instrument previously validated in European populations for measuring ON tendencies. Sixty‐five percent of the participants were Caucasian and their mean BMI was 24.4 ± 5.9, based on self‐reported height and weight. A majority of participants reported living with others (n=407, 90.8%), consuming an omnivorous diet (n=385, 85.9%), and taking supplements (n=259, 57.8%), while 41 participants (9.2%) reported consuming a specialized diet for health reasons. Of the 448 participants, 353 (81%) scored less than 40 on the ORTO‐15, indicating ON tendencies. Increased exercise frequency, younger age, vegetarian diet, and consuming a specialized diet were significant predictors of ON tendencies in this sample (p< .05). Further research is needed to confirm these results in diverse populations and to guide nutrition education efforts aimed at preventing disordered eating among college students.
Food intake reporting among adolescents using picture and text messaging with personal mobile phones (1022.1)
Authors: Siapco Gina , Sabaté Joan
Published: June 2021

Dietary assessment provides valuable information in examining adolescent health. Conventional food recording is problematic for adolescents but use of technology elicits interest. We describe in this report a food record method using personal mobile phones. Subjects were 47 females and 23 males ages 12‐18 who own mobile phones with camera. Each was given a fiducial marker (FM) with their identification number and trained on the protocol for taking before‐and‐after pictures of their meal with the FM. Subjects were randomly assigned 6 days to report within 3 months. Reminders were sent a week and the night before reporting day to prepare phones and FM. During reporting, subjects instantaneously sent pictures and text messages of foods and amounts eaten every meal to a designated email address. Research dietitians reviewed the pictures and messages the following day, resolved reported intake issues with the subject via text messaging, and collated the pictures and texts as food records. All food picture sizes were standardized relative to a specific FM length to aid in verifying amounts eaten. Records were coded later. Reviewing, collating, and recording took 30‐90 minutes/record. This novel method is suitably engaging and less burdensome to adolescents; however, researchers may not find it more time‐efficient or cost‐effective than 24‐hr diet recall by phone interview.
Rapid weight gain through age 4 y is associated with increased adiposity, higher blood pressure and insulin alterations at 4‐5 y (1024.14)
Authors: Ramírez‐Silva Claudia , Rivera‐Dommarco Juan , Trejo‐Valdivia Belem , Martorell Reynaldo , Stein Aryeh , Ramakrishnan Usha , Romieu Isabelle , Barraza‐Villarreal Albino
Published: June 2021

To evaluate the relationship between rapid weight gain (RWG) in selected periods between 1‐48 mo with adiposity, blood pressure and insulin levels at 4‐5 y of age, we studied 449 offspring of Mexican women who participated in a randomized trial in which women were supplemented with 400 mg/d DHA or placebo from mid‐pregnancy to parturition. Insulin from non‐fasting blood was obtained at 4 y, and anthropometry and blood pressure were obtained at 5 y. RWG was defined as an increase of 蠅+1.0 Z‐score weight‐for‐height within the age periods 0‐6, 6‐12, 12‐24 and 24‐48 mo. We used multivariate multiple linear models, with adjustment for DHA treatment and confounding variables (socioeconomic level, BMI of the mother during pregnancy, maternal schooling, breastfeeding at 3mo, hours of fasting, sex and height of the child). Relative to children without RWG, those with RWG at each period had higher BMI (differences ranged from 0.42 to 0.89Kg/m2; all p <0.01), sum‐of‐skinfold (range 1.1 to 3.6mm; all p<0.01) and abdominal circumference (range 1.2 to 3.8 cm; all p<0.01) at 5 y; RWG in any period from 6‐48 mo was associated with higher systolic and diastolic blood pressure (ranges 1.2 to 1.8 mmHg and 0.9 to 1.2 mmHg; all p<0.05, respectively) at 5 y. RWG in any period from 12‐48 mo was associated with 13% higher insulin levels (p<0.05) at 4 y. Children with RWG during the first 4 y had higher risk of adiposity and cardiometabolic alterations at 4‐5 y.

Grant Funding Source: NIH (HD058818; HDO43099), Mexico (CONACYT Grant number SALUD‐2008‐01‐87121).
Consumption of meat‐containing convenience foods may increase risk of obesity among adolescents (1024.18)
Authors: Bitok Edward , Alabdrabalnabi Ahmed , Siapco Gina , Sabaté Joan
Published: June 2021

Consumption of meat‐containing convenience foods may increase risk of obesity among adolescents Edward Bitok, Ahmed Al Abdrabalnabi, Gina Siapco, Joan Sabaté Department of Nutrition, School of Public Health, Loma Linda University, Loma Linda, CA 92350 Most convenience foods are characterized as energy dense, highly processed, and of poor nutrient quality. The aim of our study was to determine if the consumption of “meal‐type” convenience foods (CF) is associated with the risk of overweight/obesity among adolescents. In a cross‐sectional study, 309 females and 237 males ages 12‐18 years from 10 schools in southern California and Michigan reported their usual food intake during the past month using a web‐based food frequency questionnaire. Anthropometric measurements were obtained during school visits. BMI z‐scores (BMIZ), waist circumference (WC), and waist‐to‐height ratio (WHtR) were used as overweight/obesity indicators. Intake of meal‐type CF was classified either as meat‐containing or meatless. Data was analyzed using frequency distributions, ANOVA, and multivariate tests. 418 participants had normal BMIZ and 128 were overweight/obese. Ethnicity was a significant predictor of BMIZ, WC, and WHtR. Controlling for age, gender, ethnicity, total energy intake, and exercise, increased consumption of meat‐containing CF was significantly associated with increased BMIZ (p=.005) and WC (p=.016). Intake of total CF and meatless CF were not significantly associated with BMIZ, WC, and WHtR. The consumption of meal‐ type CF among adolescents, those containing meat but not the meatless varieties may increase risk of obesity.

Grant Funding Source: White Wave Foods
Comprehension and use of Nutrition Facts panels among young people in Canada (1025.15)
Authors: Hobin Erin , Hammond David , McVey Gail , O'Brien Mary , Sheeshka Judy
Published: June 2021

Adolescent and young adults are important populations to target for nutrition interventions given their relatively poor diets. Adolescence and young adulthood is also a period of transition, characterized by increasing independence, a growing role in food shopping, and the development of long‐term eating patterns that can track throughout adulthood. Nutrition Facts Labels are the most prominent source of nutrition information for adults in Canada; yet, very little is known about if and how young people understand and use these tools. This research sought to examine if and how young people in Canada engage with and construct meaning from information in Nutrition Facts Labels when choosing and comparing pre‐packaged foods, and test modifications to Nutrition Facts Labels. Study 1 consisted of an online survey with a sample of 2,000 young people ages 16‐24 from across Canada, including a between‐participants experiment to empirically test the efficacy of the current and modified Nutrition Facts Labels on comprehension and use of serving size and percentage daily value information when choosing and comparing foods. Study 2 used qualitative methods with a sample of 26 participants ages 16‐24 to explore the process by which young people engage with, understand, and use serving size and percentage daily value information on the current and modified Nutrition Facts Labels. These data were collected concurrently. The results from the two sub‐studies were triangulated during interpretation to facilitate a more complete understanding of young peoples’ ability to comprehend and use nutrition information on the Nutrition Facts Labels and the potential need for changes to Nutrition Facts Labels. Results will inform regulatory changes to the Nutrition Facts Label in Canada and other jurisdictions, as well as provide evidence to support interventions for improving young people’s understanding and use of Nutrition Facts Labels when choosing and comparing food products.

Grant Funding Source: Canadian Foundation for Dietetic Research
Tree nuts improve criteria of the metabolic syndrome: a systematic review and meta‐analysis of randomized controlled dietary trials (1025.6)
Authors: Kendall Cyril , Blanco Mejia Sonia , Viguiliouk Effie , Augustin Livia , Ha Vanessa , Cozma Adrian , Mirahimi Arash , Maroleanu Adriana , Chiavaroli Laura , Leiter Lawrence , de Souza Russell , Jenkins David , Sievenpiper John
Published: June 2021

Background: Chronic disease guidelines support tree nut consumption alone or as part of dietary patterns to reduce cardiovascular risk, based on their favorable LDL‐C lowering effect. The effects of nuts on metabolic risk factors other than LDL‐C, however, remain uncertain.

Aim: To assess the effect of tree nuts on criteria of the metabolic syndrome, we conducted a systematic review and meta‐analysis of randomized controlled dietary trials.

Methods: We searched MEDLINE, EMBASE, CINAHL, and the Cochrane Library (through March 19, 2013). We included relevant randomized controlled trials (RCTs) of 蠅 3 weeks reporting at least 1 criterion of metabolic syndrome. Two independent reviewers extracted all relevant data. Data were pooled using the generic inverse variance method using random effects models and expressed as mean differences (MD) with 95% confidence intervals (CI). Heterogeneity was assessed by Chi² and quantified by I². Study quality was assessed.

Results: Eligibility criteria were met by 39 RCTs including 1,676 participants who were otherwise healthy or had dyslipidemia, metabolic syndrome or diabetes mellitus. Tree nut interventions lowered triglycerides compared with control diet interventions (MD=‐0.07 mmol/L [95%CI, ‐0.11, ‐0.04 mmol/L]), but had no effects on waist circumference, HDL‐C, blood pressure, or fasting blood glucose with the direction of effect favoring tree nuts for all except HDL‐C.

Limitations: Most of the trials were of short duration (<12 weeks) and of poor quality (MQS<8). Substantial unexplained heterogeneity remained in most analyses.

Conclusions: Pooled analyses show a net benefit of tree nuts for metabolic syndrome with decreases in triglycerides across nut types and no adverse effects on other criteria. Longer and higher quality trials are needed.

Protocol registration: Clinicaltrials.gov identifier NCT01630980

Grant Funding Source: Supported by the International Tree Nut Council Nutrition Research & Education Foundation
Black currant extract attenuates ovariectomy‐induced bone loss in mice (1027.7)
Authors: Zheng Xi , Mun Sewhan , Lee Sang Gil , Vance Terrence , Hubert Patrice , Koo Sung I. , Lee Sun Kyeong , Chun Ock
Published: June 2021

Bone remodeling is orchestrated by osteoblasts and osteoclasts in response to changes in redox status, inflammatory cytokines, and hormones. Several animal and cell studies indicate that black currant (BC) exerts antioxidative and anti‐inflammatory properties, which could potentially improve bone mass. This study was aimed to evaluate the effect of BC on bone mass and structure in a mouse model of ovarian hormone deficiency. 14‐wk old C57BL/6J mice were ovariectomized (OVX) or sham operated. The OVX mice were divided into two groups; OVX fed a basal diet (control) and OVX fed the same diet but with 1% BC extract (provided by the Just The Berries LTD), and sacrificed at 4, 8, and 12 wk. Femoral bone mineral density (BMD) and trabecular bone volume (TBV) by DXA and micro‐CT and serum bone markers were determined. OVX significantly reduced BMD and TBV (p<0.05) at all time points. At 8 and 12 wk, BC supplementation attenuated OVX‐induced BMD and TBV. OVX and BC treatment did not alter serum biomarkers of bone formation and resorption. Additionally, we tested if BC supplementation affects osteoclast like cell (OCL) formation in bone marrow (BM) cell cultures. BM cells from OVX significantly induced OCL formation compared to cells from sham controls (P<0.05). BC treatment decreased the number of TRAP(+) OCL compared with OVX at 8 and 12 wk (P<0.05). Furthermore, BC supplementation reduced bone resorption activity when measured by resorption pit assay, compared with OVX group (P<0.05). These results show that BC is effective in mitigating osteoclast‐induced bone loss accelerated by ovariectomy.

Grant Funding Source: this study was supported by the University of Connecticut USDA Hatch Grant.
Synergistic effects of leucine with phosphodiesterase 5 inhibition on insulin sensitivity (1035.4)
Authors: Fu Lizhi , Li Fenfen , Bruckbauer Antje , Cao Qiang , Cui Xin , Wu Rui , Shi Hand , Zemel Michael , Xue Bingzhong
Published: June 2021

Leucine activates Sirt1 signaling and markedly potentiates the effects of other activators on sirtuin signaling and downstream effects, including insulin signaling. PDE5 inhibition increases NO‐cGMP signaling, converging with sirtuins on PGC‐1 and mitochondrial biogenesis and thereby modulating insulin sensitivity. We confirmed this synergy in vitro, demonstrating synergy between leucine (0.5 mM) and two PDE5 inhibitors, sildenafil and the natural flavonol icariin (0.1‐10 nM) on aerobic metabolism, mitochondrial biogenesis and insulin sensitivity in myotubes and adipocytes. Effects on insulin sensitivity and glycemic control were then assessed in diet‐induced obese mice. High fat diet (HFD) for six weeks induced pronounced fasting and post‐prandial hyperglycemia and insulin resistance which was not significantly affected by addition of leucine (24 g/kg) or icariin to the diet. However, adding icariin at a level that produces no independent effect (25 mg/kg diet) to the high leucine HFD for 6 weeks reduced fasting glucose (38%, p<0.002), insulin (37%, p<0.05) and area under the glucose tolerance curve (20%, p<0.01). In addition, glucose response to an insulin challenge was impaired by HFD and fully restored by addition of leucine+icariin. These robust improvements in glycemic control and insulin sensitivity indicate therapeutic potential for this combination.

Grant Funding Source: Supported by NuSirt Sciences, Inc.
Effects of high fat diet‐induced obesity on expression of genes involved in vitamin D metabolism in mice (1041.11)
Authors: Park Jeong Min , Park Chan Yoon , Han Sung Nim
Published: June 2021

Low vitamin D status has been often reported in obese human, however, the mechanism still remains unclear. Expression of genes involved in vitamin D metabolism was investigated in high fat diet‐induced obese mice to understand the effect of obesity on vitamin D status and metabolism. Four‐wk‐old C57BL mice were fed control diet containing 10% energy fat from soybean oil (Control) or high‐fat diet with 45% energy fat from 10% soybean oil and 35% lard (HFD) for 18 wks. mRNA levels of 25‐hydroxylases (CYP2R1, CYP27A1, CYP2J3) in liver and adipose tissue, and 24‐hydroxylase (CYP24A1) and 1α‐hydroxylase (CYP27B1) in kidney were determined by real‐time PCR. Serum 25‐hydroxyvitamin D (25(OH)D) level was analyzed by radioimmunoassay. HFD group gained more weight and had more adipose tissue than Control group. HFD group had significantly lower hepatic CYP2R1, CYP27A1 and CYP2J3 mRNA levels (31%, 30% and 48% lower, respectively). But in adipose tissue, CYP27A1 and CYP2J3 mRNA levels were significantly higher in HFD group (68% and 126% higher, respectively). Renal CYP24A1 mRNA level was downregulated (P=0.02), and CYP27B1 mRNA level tended to be upregulated (P=0.07) in HFD group. There was no difference in serum 25(OH)D level between two groups. In conclusion, expression of genes involved in vitamin D metabolism can be altered by HFD‐induced obesity. Expression of hepatic vitamin D activating enzyme and renal vitamin D degrading enzyme were downregulated.

Grant Funding Source: Supported by the grant from the National Research Foundation (NRF) of Korea (NRF‐2010‐0024878)
Dynamic vitamin A metabolism contributes to the regulation of hepatic glucose and lipid metabolism in response to different physiological conditions (1041.13)
Authors: Li Yang , Chen Guoxun
Published: June 2021

Vitamin A (VA) and its metabolites are essential for human health. Retinoic acid (RA) modulates insulin‐regulated expression of hepatic genes for glucose and lipid metabolism in primary rat hepatocytes. We also found that elevated RALDH1 expression in the liver of Zucker fatty rats may cause the excessive RA production resulting in increased lipogenesis. Here, we hypothesize that cellular VA pool, either from dietary sources or hepatic storage, affects the responses of nutrients and hormones levels to different physiological and disease conditions through regulating the expression of genes involved in hepatic glucose and lipid metabolism.

Male Zucker lean rats were fed with a VA deficient (VAD) or a VA sufficient (VAS) diet for 8 weeks. Then they were subjected to the fasting‐refeeding cycle or induced type 1 diabetes by streptozotocin treatment. Respiratory exchange ratio was measured by indirect calorimetry. Plasma parameters were measured using commercial kits. Protein and mRNA levels were respectively examined by Western blot and real‐time PCR. VA status affected energy expenditure of the rats. Responses of plasma insulin and leptin levels to different physiological and disease conditions were altered in VAD rats compared to that in VAS ones. The expression levels of ACC, FAS, ACL, SREBP‐1c, PEPCK, and GCK, were regulated by VA status at both mRNA and protein levels. We conclude that dietary VA and its hepatic metabolism contribute to the regulation of plasma hormone levels and hepatic gene expression in rats.

Grant Funding Source: Supported by American Heart Association
Dietary resistant starch prevents urinary excretion of vitamin D metabolites and restores circulating 25‐hydroxycholecalciferol concentrations in the Zucker diabetic fatty rat (1041.3)
Authors: Koh Gar Yee , Mancosky Kirsten , Loo Yi‐Ting , Grapentine Kelly , Bowers Emily , Rowling Matthew
Published: June 2021

Type 2 diabetes (T2D) is an epidemic that leads to renal disease if left untreated. Compromised renal function has been implicated in vitamin D deficiency as the renal proximal tubule maintains circulating 25‐hydroxycholecalciferol (25D) concentrations as well as its activation to 1,25‐dihydroxycholecalciferol (1,25D). We previously showed that feeding high‐amylose maize that is partially resistant to digestion (RS) prevented excretion of 25D‐vitamin D‐binding protein (DBP) and albumin in T1D rats. Here, we utilized Zucker diabetic fatty rats (ZDF) to determine whether dietary RS could prevent excessive excretion of vitamin D metabolites and maintain serum 25D level. Lean control Zucker (n=8) rats were fed a control diet (AIN‐93G) and ZDF were fed either the AIN‐93G diet (n=8) or the AIN‐93G diet in which cornstarch was replaced by RS (n=8) for 6 week. RS attenuated hyperglycemia by 41% and prevented excretion of DBP and albumin. Urinary 25D and 1,25D concentrations were 89% and 97% lower, respectively, while serum 25D levels were 40% higher in RS‐fed ZDF compared to ZDF fed the control diet. mRNA expression of CYP27B1 and CYP24A1, which are essential in vitamin D metabolism, were not affected by diabetes or RS. Collectively, these data suggested that vitamin D balance is dependent on the absence of proteinuria, which can be prevented by dietary RS in T2D independent of vitamin D supplementation.
Antibiotics that prevent endotoxemia do not reduce the ability to ferment high amylose maize resistant start (HAMRS2) in rats (1044.11)
Authors: Carvajal‐Aldaz Diana , Coulon Diana , Chaves Tyler , Raggio Anne , Martin Roy , Stoutt Rhett , Gauthier Ted , Durham Holiday , Pelkman Christine , Keenan Michael
Published: June 2021

The gut microbiota affects health. Research with antibiotics (ampicillin 1 g/L, and neomycin 0.5 g/L in drinking water) reduced bacterial DNA and endotoxemia in mice fed high fat diet or ob/ob mice fed chow. The antibiotics reduced Lactobacillus, Bifidobacterium, and Bacteroides spp. Several of these ferment HAMRS2. We tested if these antibiotics prevented fermentation of HAMRS2 in rats. Phase 1 consisted of feeding two groups of rats with either HAMRS2 diet without antibiotics (n=10) or a diet with no fermentable carbohydrates with antibiotics (n=19). After 3.5 weeks, 5 rats from each group were euthanized for cecal content pH and short chain fatty acid (SCFA) analysis. An additional 5 rats on the HAMRS2 diet were euthanized where their cecal contents were pooled. The cecal pH was significantly lower (p<0.05) for the group fed HAMRS2 while the other group produced very low SCFA. The remaining rats (14), fed with antibiotics and no HAMRS2 were split into two groups, one of which was gavaged with the previously pooled cecal contents (n=7) while the others were gavaged with water (n=7). Thereafter both groups were fed HAMRS2 diet for 3.5 weeks. After the second phase, cecal content analysis indicated both groups fermented HAMRS2 while pH and production of SCFA were not different. Our results suggest antibiotics used to control metabolic endotoxemia do not alter HAMRS2 induced fermentation.

Grant Funding Source: Supported by Ingredion, Inc. and LSU AgCenter
A quercetin nanoemulsion enhances oral bioavailability and hepatic accumulation of quercetin (1044.19)
Authors: Guo Yi , Tran Thanh Huyen , Lu Xiuling , Bruno Richard
Published: June 2021

Quercetin (Q) has antioxidant activity but poor bioavailability. We examined whether a quercetin nanoemulsion (NQ) improved Q bioavailability and its hepatic accumulation. Rats received NQ or unformulated Q (UQ; 30 mg/kg BW) by gavage prior to collecting plasma at timed intervals for 24 h to measure Q and its methylated metabolites isorhamnetin (ISO) and tamarixetin (TAM). Rats receiving NQ or UQ were also sacrificed at 4 or 24 h to measure liver Q, ISO, and TAM. Compared to UQ, NQ increased (P<0.05) maximum plasma Q (21.5 ± 5.1 vs 7.7 ± 2.0 µM) and Q bioavailability (AUC0‐24 h: 130.4 ± 30.9 vs 57.2 ± 19.6 µM x h). NQ decreased Q time to maximum concentration (0.9 ± 0.3 vs 3.8 ± 1.0 h, P<0.05) while increasing Q half‐life (7.2 ± 1.1 vs 4.5 ± 0.5 h, P<0.05). Plasma pharmacokinetics of ISO and TAM were unaffected by NQ. NQ increased liver Q (233 ± 28 vs 159 ± 28 pmol/g) and liver ISO (120 ± 14 vs 78 ± 15 pmol/g) to a greater extent at 4 h than UQ whereas hepatic Q and ISO were similarly lowered at 24 h without any group differences. Liver TAM at 4 h did not differ between groups nor was it detected at 24 h in either group. Plasma alanine transaminase and creatinine were unaffected by both treatments. Collectively, NQ improves Q oral bioavailability without inducing acute liver or renal injury. Further study is needed to examine whether greater hepatic accumulation of Q or ISO potentiates their antioxidant activity.

Grant Funding Source: Supported by the Diet and Health Initiative at University of Connecticut
Assessment of nutritional status in subjects of non‐MonaVie product users, before and after supplementation ő a longitudinal study (1044.20)
Authors: Quan Danyi , Xiong Wade , Talbott Shawn
Published: June 2021

BACKGROUND: An antioxidant is a molecule that inhibits the oxidation of other molecules. Oxidation reactions can produce free radicals that cause various diseases. Antioxidants can inhibit the oxidation reactions and increase the body's immune system. To boost antioxidant levels, the human body relies on a healthy diet. However, very few people eat enough fruits and vegetables to provide their bodies with sufficient levels of antioxidants. To fill in the nutritional gaps of modern diets, many people turn to supplementation. OBJECTIVE: This is a continuation study in non users from the cross sectional study; we evaluated the improvement on skin and plasma levels of carotenoids in subjects of non MonaVie product users after 8‐week MonaVie juice consumption. METHODS: Total 33 non users from the cross sectional study were enrolled; 18 subjects having MonaVie juice formulated with proprietary carotenoid powder blend; 15 subject having MonaVie juice formulated with commercial carotenoid granules. All subjects had the weekly reflectance score measurements. and blood draw was taken at t=0 and 8 weeks. The plasma concentration of carotenoids were extracted and assayed by validated extraction and HPLC methods. RESULTS: The group having juice with proprietary carotenoid blend showed a good correlation between reflectance scores as well as the plasma beta carotene concentration (before r2 = 0.44 vs. after r2 = 0.44); while the group having juice with commercial carotenoids showed no correlation between reflectance scores and plasma beta carotene concentration (before r2 = 0.37 vs. after r2 = 0.095). CONCLUSION: The results show that both skin carotenoid levels and plasma carotenoid concentration were increased significantly after 8 week consumption of MonaVie juices; The juice with the proprietary carotenoid blend showed a good correlation between skin levels and plasma concentrations, suggesting a consistent and stable absorption rate and good bioavailability.
Anti‐adipogenic and anti‐inflammatory mechanism of nobiletin in co‐culture of adipocyte and macrophage (1045.13)
Authors: Lee Junsoo , Namkoong Seulgi
Published: June 2021

Adipose tissues are characterized by the enhanced infiltration of macrophages. It is considered that the paracrine loop between adipocytes and macrophages establishes a vicious cycle that aggravates inflammatory changes and insulin resistance in obese adipose tissues. Nobiletin is abundantly present in the fruit peel of Citrus and has several health beneficial effects including antioxidant, anti‐inflammation and anticancer activities. However, not much is known about the anti‐adipogenic and anti‐inflammatory effect of nobiletin in co‐culture system of adipocyte and macrophage. The objective of this study was to evaluate the inhibitory effect of nobiletin on the interaction between adipocytes and macrophages. The results revealed that nobiletin markedly inhibited NO, TNF‐α and MCP‐1 secretion in contact and trans‐well systems of adipocytes and macrophages in a dose‐dependent manner. In addition, nobiletin blocked the expression of adipogenic transcription factors, including PPARγ, C/EBPα and aP2 in 3T3‐L1 cells of transwell system. Also, nobiletin inhibited the expression of iNOS in RAW264.7 cells. These results indicate that nobiletin exhibits anti‐adipogenic and anti‐inflammatory properties in the interaction of adipocytes and macrophages. Nobiletin may be useful for ameliorating the adipogenic and inflammatory changes in obese adipose tissues.
Granzyme B contributes to extracellular matrix degradation in UV‐treated skin (1046.1)
Authors: Parkinson Leigh , Toro Ana , Granville David
Published: June 2021

Extracellular matrix (ECM) degradation is a hallmark of many chronic inflammatory diseases that can lead to a loss of function, aging and disease progression. Granzyme B (GzmB), a serine protease that is expressed by a variety of cells, has been shown to accumulate in the extracellular space during chronic inflammation and cleave a number of ECM proteins. Using a model of UV‐induced chronic inflammation in the skin, we hypothesized that GzmB contributes to ECM degradation through both direct cleavage of ECM proteins and indirectly through the induction of other proteinases, which leads to a phenotype of aged skin. Wild‐type and GzmB‐knockout (KO) mice were repeatedly exposed to minimal erythemal doses of solar simulated UV‐irradiation for up to 20 weeks. GzmB expression was significantly increased in wild‐type treated skin compared to controls. GzmB deficiency significantly protected against the formation of wrinkles and the loss of dermal collagen density, which was related to the cleavage of decorin, an abundant proteoglycan involved in collagen fibrillogenesis and integrity. GzmB also cleaved fibronectin, and fibronectin fragments have been shown to increase the expression of collagen‐degrading matrix metalloproteinases (MMPs) in fibroblasts. Collectively, these findings indicate a significant role of GzmB in ECM degradation, which may have implications in many chronic inflammatory diseases.

Grant Funding Source: Supported by CIHR
The inhibitory effect of sinigrin on the production of inflammatory mediators induced by lipopolysaccharide in RAW 264.7 macrophages (1056.5)
Authors: Lee Heeweon , Lee Chunggi , Kim Jiyun , Pyo Suhkneung
Published: June 2021

Sinigrin (2‐propenylglucosinolate) is a biochemical nutrient found naturally in some plants of the Brassicaceae family such as broccoli, Brussels sprouts. Recent studies showed that sinigrin affect the preventing of cancer in preclinical or clinical trials for cancer chemoprevention. However, anti‐inflammatory effect of sinigrin was unknown. In the present study, we examined the effects of sinigrin on the production of inflammatory mediators in lipopolysaccharide (LPS)‐activated RAW 264.7 macrophages. The cell viability was determined by MTT assay. We investigated the anti‐inflammatory effects of sinigrin on Nitrite Oxide (NO) and pro‐inflammatory cytokine production by colorimetric assay and ELISA assay, respectively. We also examined the expression of MAPK, NLRP‐3 and p65 by Western blot. The results showed that NO production was not reduced by sinigirn.

Whereas, sinigrin inhibited the levels of tumor necrosis factor‐ α (TNF‐α) and interleukin‐6 (IL‐6). Sinigrin blocked phosphorylation of JNK and p38, but not that of ERK. In addition, sinigrin treatment significantly suppressed the expression of p65 and NLRP‐3 compared with the control. These finding suggest that sinigrin has an anti‐inflammatory effects, which may result from inhibition of MAPK phosphorylation, and the expression of NLRP‐3 and p65, thereby decreasing the production of pro‐inflammatory mediators.
Novel nAChRs modulators for treating CNS disorders: discovery of AChBP cooperative ligands (1059.7)
Authors: Kaczanowska Katarzyna , Harel Michal , Finn M.G. , Taylor Palmer
Published: June 2021

nAChRs are pentameric molecules formed from identical or homologous subunits to form homomeric and heteromeric assemblies. They play a critical role in the peripheral and central nervous systems to mediate neurotransmission by acetylcholine and, as such, are critical targets for understanding nicotine addiction and developing useful drugs for treating CNS disorders such as schizophrenia, Parkinson’s disease and disorders of dementias. The acetylcholine binding protein (AChBP) is a pentameric structural homologue of the extracellular ligand‐binding domain of nAChRs. Up until recently, this approach has yielded compounds that bind as would be predicted by a equivalent set of five sites in the pentameric molecule, a situation also seen with classical natural product agonists and antagonists binding to the AChBP. Very recently through our synthetic program, we have uncovered a set of new structures that exhibit cooperativity, where many show Hill slopes greater than 1.0 or considerably less than 1.0. The latter is not due to heterogeneity of the binding protein template, since AChBP has five identical sites as examined crystallographically and by conventional ligand binding. Through the structural analysis, we can delineate the structural features of the ligands inducing this new mode of association with the extracellular domain of the receptor. Our approach of finding a series of ~50 congeneric ligands where individual members can be distinguished by positive and negative cooperativity should shed new light on subunit interactions in this homopentamer. For example, cooperative interactions appear to link in a circumferential fashion around the perimeter of the extracellular domain and do not necessarily require a direct connection with the channel gate area to elicit subunit interactions. This unique feature of our series of ligands gives a high promise to develop medications with distinct pharmacological profiles.

Grant Funding Source: TRDRP (21FT_0024); NIH (GM 18360)