bluuebunny/crossref_metadata_2025 huggingface dataset:
Membrane localization of metabolic enzyme and metabolic modulation in the Δmin mutant of Escherichia coli
Authors: Shih Yu‐Ling , Hung Chun‐Hsien , Wang Chung‐Kang
Published: November 2023

It is generally believed that membrane association of a protein could cause conformational changes thus modulating its function. Our recent quantitative proteomic study suggested that a membrane‐associating protein oscillator, the E. coli Min system, may play a role in modulating membrane interaction and function of proteins. Functional analysis of the proteomic dataset revealed enrichment in metabolic enzymes, i.e. a significant number of metabolic enzymes were among the proteins affected by the Min system. In line with this observation, we identified imbalance of several metabolites in the Δmin mutant that were catalyzed by the enzymes identified in the functional enrichment analysis. The results suggested that the metabolic modulation may be an adaptive phenotype in the Δmin mutant, due to a modulated abundance of proteins on the inner membrane. Thus the membrane‐associating Min oscillator may have a global physiological impact in E. coli through regulating membrane association of proteins. To obtain direct evidence, we are focusing on selected enzymes of the glycolytic pathway to study their involvement in cell division by characterizing the cell division phenotypes and studying their subcellular localization.

Support or Funding Information

Academia Sinica, Taiwan
Hydrophobic region of Marburg Virus may indicate mechanism of protein trafficking to plasma membrane
Authors: Wijesinghe Kaveesha , McVeigh Luke , Stahelin Robert
Published: November 2023

Ebola virus and Marburg virus has high fatality rate in humans and to date there are no FDA approved vaccines or therapeutics to treat it. Viral protein 40 (VP40) is the major virus matrix protein of these viruses that regulates assembly and egress of infectious Ebola and Marburg virus particles. It is well established that Ebola VP40 interacts with the inner leaflet of the plasma membrane using anionic phospholipids and penetrates into the hydrocarbon core of the plasma membrane. Marburg VP40 also interacts with anionic phospholipids at the inner leaflet of the plasma membrane but unlike Ebola VP40 its interaction is highly dependent on anionic charge density of the plasma membrane. Marburg VP40 protein did not have hydrophobic interactions with the hydrocarbon core of the plasma membrane despite it having a structurally similar hydrophobic loop region to Ebola VP40, which penetrate the plasma membrane. To investigate the function of this hydrophobic loop region of Marburg VP40, we created single double and triple amino acid mutants of this region specifically targeting L201, F281, L283, and F286 residues and observed the phenotype of the cells transfected with these mutants using a GFP tag. The single amino acid mutant L201A along with the double mutant (F281A/F286A) and triple mutant (F281A/L283A/F286A) resulted in localization of VP40 into intracellular accumulations that had vesicular structures, while all other mutants maintained the Wild Type phenotype by associating with the plasma membrane. When these mutants were co‐expressed with Early Endosome Antigen 1 (EEA1) protein it led to complete dissociation of these mutants from vesicle structures to become entirely cytosolic. EEA1 protein is early endosomal marker that interacts with phosphoinositide‐PI3P and Rab5 protein on early endosomes. Our observation suggests that these mutants are associated with early endosomes by likely interacting with PI3P and their mutant phenotype is likely to represent inability of these mutants to be trafficked to the plasma membrane. Marburg VP40 is known to use retrograde late endosomal pathway accumulating at multivesicular bodies (MVBs) before reaching the plasma membrane. Therefore, these mutants are likely to represent an early step of Marburg VP40 trafficking to plasma membrane and may provide valuable insight into Marburg VP40 membrane trafficking pathway.
Serve Yourself from Overeating: Pre‐Served Portions Lead to Uniform Eating Across Distraction Levels
Authors: Tal Aner , Wansink Brian
Published: November 2023

Following up on Tal et al. (2014), this study examines whether receiving pre‐plated portions, as opposed to self‐serving, changes the effects of distraction on eating. We predicted that when given pre‐plated amounts, participants would eat as much regardless of the nature of distraction

Participants (N = 200) snacked on three types of snacks while watching 20 minute programs. This sample includes the Tal et al. (2014) sample as well as a separate participant sample run in parallel. Half of the participants were served pre‐plated bowls of grapes, baby‐carrots, M&Ms and cookies (150 grams each), and half served as much of each snack as they desired. Each of the two groups was divided to three: A third of participants watched action movie “The Island,” a third watched “The Island” without sound, and a third watched “The Charlie Rose Show”. We compared the amounts of snacks consumed by each condition.

For participants serving themselves, quantities eaten were 104.29 grams (214.58 calories) with Charlie Rose, 142.09 grams (314.48 calories) with The Island without sound, and 206.53 grams (354.13 calories) with The Island, as reported in Tal et al. (2014). However, for those receiving pre‐plated snacks, amounts consumed showed no difference across conditions. Participants who watched Charlie Rose consumed 214.88 grams (357.19 calories), those watching The Island without sound consumed 191.46 grams (325.54 calories), and those watching The Island with sound consumed 184.73 grams (280.73 calories). The effect of pre‐plating was significant at a .003 level: F(1,194)=13.37, p=.0003. Pre‐plating participants ate more than those serving themselves (196.45 vs. 151.46 grams, 319.34 vs. 295.03 calories). There was also significant effect of viewing content at a .05 level: F(1,194)=3.09, p=.05. finally, the interaction of content and pre‐plating was significant at a .0002 level: F(2,194)=9.21, p=.0002. There was no significant difference in amounts eaten when snacks were pre‐plated.

Past research has shown that participants consume more food the more distracting the content they watch (Tal et al. 2014). However, in that study participants determined their own consumption amounts. The current study showed that receiving identical pre‐plated amounts eliminates the effects of level of distraction on food consumption. Participants uniformly ate more, with no influence of program, when given pre‐plated, pre‐determined quantities of food. Receiving pre‐portioned snacks can lead to mindless eating where participants eat greater amounts of food, while serving themselves can allow consumers to monitor and curb consumption, though not when highly distracted.
A Ketogenic Diet Prevents Abnormal Changes in Peripheral Nerve Function Caused By A High‐Fat Diet
Authors: Cooper Michael , Ryals Janelle , Wright Doug
Published: November 2023

Mice given ad libitum access to a diet with high‐fat (54% kcal from fat) content begin to display clinical symptoms of prediabetic patients, including obesity, hyperglycemia, and mechanical allodynia. The molecular changes that underlie changes induced by a high‐fat diet that lead to neuropathic symptoms have yet to be identified. Our work has shown that mice given access to a running wheel while on a high‐fat diet develop mechanical allodynia over the first 6 weeks, which is then rescued to baseline levels during weeks 6–12. The current study examined how a ‘ketogenic’ diet (~90% kcal from fat) may alter prediabetic clinical symptoms to better understand how fat processing may impact the development of pre and overt diabetes, as well as to better understand the mechanism through which exercise may provide its benefits on high‐fat induced mechanical allodynia. Contrary to mice on a high‐fat diet, ketogenic fed animals never developed mechanical allodynia, suggesting maladaptations to utilizing carbohydrates as a fuel source may be key in leading to mechanical allodynia. Sensory nerve conduction velocities were also examined and mice fed a high fat diet displayed faster sensory conduction velocities compared to ketogenic and control mice. Motor nerve conduction velocities were also significantly faster in high‐fat sedentary and exercise mice, but were not changed in mice fed a ketogenic diet. Ketogenic diet‐fed mice displayed increased body weight and hyperglycemia, mirroring levels seen in high‐fat fed mice given access to exercise. Analyses of fat mass by percent of total mass revealed that both ketogenic‐diet fed and exercised mice had lower fat mass compared to high‐fat sedentary mice. Intriguingly, ketogenic‐diet fed mice had elevations in peripheral nerve fiber density in the hind paw relative to both normal chow and high‐fat fed mice. Together, these results suggest that a ketogenic diet is able to correct many of the clinical symptoms of high‐fat fed prediabetic mice, and importantly, mirrors many changes that can be corrected by exercise in in high‐fat fed mice.

Support or Funding Information

This work was supported by the NIH grants P20GM1033418 and RO1NS43314 (D.E.W)
Inadequate zinc and calcium but adequate iron intakes in lactating women from southern Ethiopia
Authors: Girma Meron , Seid Haider , Tilahun Birkneh , Stoecker Barbara J
Published: November 2023

Inadequate intake of micronutrients during lactation can compromise nutritional status of mothers and infants and lead to concurrent multiple micronutrient deficiencies. We assessed dietary intake of lactating women (n=119) in Southern Ethiopia to determine the prevalence of inadequate intakes for selected nutrients. One‐day weighed food records were analyzed for average energy and nutrient intakes for the group. A nonconsecutive second day weighed record was repeated in a sub sample of participants (n=40) to estimate with‐in and between person variation in nutrient intakes. Prevalence of inadequate intakes was then estimated with Intake Monitoring, Assessment and Planning Program (IMAPP) software. The EAR‐cutoff method based on the WHO/FAO Recommended Nutrient Intakes was used to evaluate inadequate intakes. Median (IQR) energy (kcal) intake for the group was 1649 (1282, 2133). Median intakes for Protein (g): 32 (25, 44), Vitamin C (mg): 3 (1,9), Vitamin A (RAE): 87 (21, 460), Ca (mg): 627 (389, 885) and Zn (mg): 9 (6, 11) were below recommendations. The median phytate: Zn ratio was 22 (19, 23) and phytate: Fe ratio was 5 (4, 6). Prevalence of inadequate intake was 100% for Vitamin C, 94 % for Vitamin A, 70 % for Ca and 21 % for Zn. In contrast, Fe intake was adequate for all mothers. The high to moderate prevalence of inadequacy for multiple micronutrients and low bioavailability of micronutrients from the diet emphasizes the need for continued interventions to improve diet diversity in these communities.

Support or Funding Information

Supported by the Nutricia Research Foundation and OAES Regional Project W‐3002.
Reinforcement as a Parenting Strategy Related to Children Obesogenic Behaviors Is Associated to Mothers’ but not Fathers’ Education Level among Health Workshop Participants in Mexico City
Authors: Perez‐Lizaur Ana Bertha , Fernandez‐Gaxiola Ana Cecilia , Damacio Ma Jose , Moreno‐Landa Luz Irene
Published: November 2023

Family environment and parental strategies can shape their children eating and health behaviors. However, little has been documented about the parenting strategies in Mexico, particularly related to food intake, physical activity and sedentary behaviors in the home.

Objective

To asses parenting strategies in parents and caregivers and its relationship to socioeconomic factors.

Methods

We did a cross‐sectional survey of 316 parents and caregivers who were attending workshops held by community health workers in poor urban areas in Mexico City with a previously validated, self‐administered questionnaire. We analyzed associations between parenting styles and socioeconomic factors with logistic regression.

Results

Most participants were mothers (71.8%), grandparents (13.6%) and uncles/aunts (4.4%). Mean ± SD age was 40.36±11.87 years and middle school was the most frequent schooling achieved by both fathers (34.2%) and mothers (41.8%). Mean ± SD number of family members living in the same household was 4.79±2.13 persons, including parents, children and usually other relatives. Limiting, monitoring and reinforcement were the most frequent parenting strategies used by the parents/caregivers. Control and discipline strategies are less used. We found a significant positive association with the used of Reinforcement and schooling of mothers (p=0.048) that explains only 5% of these strategy.

Conclusions

Mothers' schooling is a determinant in the use of reinforcement, which is an important positive strategy for influencing food intake, physical activity and sedentary behaviors in children. Negative strategies for influencing these behaviors are not frequently used. Parenting strategies can provide a framework for designing interventions for the prevention of obesity related behaviors at home level.

Support or Funding Information

Fundación SERTULL AC
Development and Testing of a Pilot Integrated Mental Health and Nutrition Education Program for Low‐Income Families in Southern California
Authors: Spitz Rachel P , Kim Loan Pham , Gavazza Judy Ho
Published: November 2023

The Special Supplemental Nutrition Program for Women, Infants, and Children (WIC) is a federally funded nutrition program which provides nutrition education, breastfeeding support, and a supplemental food package for low‐income mothers and children up to the age of five. Nationwide, approximately 25% of the individuals served are women, 25% are infants and the remaining 50% are children ages one to five. WIC services are available in every state and US territory, and currently WIC services are delivered to over 8 million participants each month. In Los Angeles County (LAC), WIC currently serves approximately 67% of all infants and about half of all children ages one to five, translating into approximately 500,000 individuals and 350,000 families each month. While nutrition education is a vital public health service for mothers and their children, a significant unmet need is for mental health support services for WIC participants. In 2014, an LA County survey of WIC families found that 13.6% of WIC mothers reported experiencing depressive symptoms, which included feeling down, depressed or hopeless, or having little interest or pleasure in doing things. Mental health factors such as stress and depressive symptoms are associated with poor food choices and obesity, particularly in low‐income households. Because WIC is a nutrition program, it is not staffed to provide mental health support services. However, many women would benefit from support to alleviate stress and depressive symptoms. The purpose of this Healthy Body and Mind pilot project was to fill this unmet need through a university and service delivery partnership to provide a holistic mental health, life skills, and nutrition education program to WIC participants in LA County. The six‐session program is based on Cognitive Behavioral Theory and developed in the form of reusable modules and handouts. These support groups will be delivered by advanced graduate students in psychology, under the supervision of nutrition and psychology faculty. In this presentation, we will discuss content development of the curriculum, provide an overview of the graduate and undergraduate training model, and share preliminary results of two pilot support groups, one that meets weekly for six weeks, and another that meets monthly for six months. Finally, we will discuss possible implications for future potential university and service delivery models of mental health support programs within WIC

Support or Funding Information

This research is funded by the Pepperdine Community‐Based Participatory Research (CBPR) grant, 2016.
Families with Preschool Children Meet Behavior Change Goals Using the HomeStyles Express Breakfast the Right Start Guide Paired with Telephone Counseling
Authors: Delaney Colleen , McKinley Jessica , Martin‐Biggers Jennifer , Byrd‐Bredbenner Carol
Published: November 2023

This study aimed to describe the effectiveness of the HomeStyles Express Breakfast the Right Start guide coupled with a telephone counseling session in aiding families with pre‐school children have breakfast daily to promote weight management. Parents (n=41) completed a baseline survey, received 1 of 8 different instructional guides/week and chatted weekly via telephone with a dietitian. Most participants were white (76%), female (95%), and were college graduates (90%). At baseline, parents were confident that they could get their preschoolers to eat breakfast daily (mean=4.51±0.81SD, on 5‐point scale), yet reported eating breakfast together as a household just 3.76±2.74SD days/week. The Breakfast the Right Start guide describes how daily breakfast is an important weight‐management behavior and provides tips for making breakfast a reality each day. Content analysis of counseling sessions found that, after reading the guide, many planned to begin offering children more options at breakfast and start planning breakfast meals. Parents also were better able to describe the importance of breakfast (e.g., improved mood, satiety, more quality family time). After reading the guide, many intended to eat breakfast together as a family more often, offer children a greater variety of healthful options at breakfast, and prepare for breakfast ahead of time. Some also set goals to communicate the importance of breakfast to their families and spouses. Parents were very confident in their ability to meet these goals (mean=8.63±1.46SD, on 10‐point scale) and at subsequent counseling sessions, most reported successfully meeting goals. The Breakfast the Right Start guide, along with a telephone counseling session, has the potential to successfully aid families in having breakfast daily and, thus, better manage body weights.

Support or Funding Information

USDA NIFA #2011‐68001‐30170
The Victoria Trial: A School‐Based Health Education Program to Reduce the Risk of Obesity Among a High‐Risk Population
Authors: Mejia Maximino Alfredo , Coria‐Navia Anneris , Uriegas‐Mejia Griselda , Brown‐Fraser Sherine C , Uriegas Sergio E , de Jesus Martinez Maria , Sanchez Albert , Acosta Maria Elena , Ramirez Armando E , Reyes Rembrandt E , Hernandez Yadyra C , Camacho Dacia Y , Morrow Gregg , Krivak Gretchen
Published: November 2023

Background

Childhood obesity is a major global public health problem which disproportionately affects Hispanic children in the United States and Mexico. Many school‐based interventions have been tested to address this issue. Amate, Activate, Cuidate, Comparte (AACC) [Love Yourself, Activate Yourself, Take Care of Yourself, and Share] is a new culturally sensitive health education model to prevent child obesity.

Methods

In an attempt to curve the obesity epidemic among school‐aged children in Mexico, the AACC model was pilot tested in two schools that have a high rate of overweight (30%) and obesity (26%) in Tamaulipas, Mexico. Those schools were randomly assigned to experimental and control groups. Third and fourth grade children were the focus of this intervention. Children in the experimental school received nutrition education, daily physical activity, and a modified school‐lunch while children in the control group had no intervention. The AACC curriculum is based on psycho‐pedagogical theory, including social cognitive theory and positive psychology. This model was developed and implemented through the collaborative work between Andrews University, and the Secretaría de Salud, and the Secretaría de Educación Pública of the State of Tamaulipas, México. The intervention targeted teachers, children and parents. Changes in anthropometric measurements (such as Body Mass Index (BMI) were assessed pre‐post intervention. We targeted 10 behaviors to reduce calorie density in the diet and one hour of daily physical activity to enhance energy expenditure.

Results

The upward trend of BMI was reversed among children with overweight/obese in the experimental group while the upward trend of the BMI in the control group continued to increase. These changes are not statistically significant after four months.

Conclusion

This preliminary data suggests that the AACC model could be effective in preventing obesity among school‐aged children in the Hispanic Population. This model needs further testing in more schools for longer time.

Support or Funding Information

Secretaria de Salud Tamaulipas, Secretaria de Educacion Tamaulipas, Office of Research and Creative Scholarship, Andrews University
Effects of a 12‐week Telenutrition Weight Loss Intervention on Diet Quality in Men
Authors: Kapostasy Alexis , Drazba Margaret , Shotwell Matthew , Marra Melissa Ventura
Published: November 2023

Poor diet and obesity are independent risk factors for type 2 diabetes, hypertension and cardiovascular disease. This study used a randomized controlled trial design to pilot test the effect of a 12‐week home‐delivered telenutrition weight loss program on diet quality in 40–70 year old men with obesity, waist circumference >40 inches and at least one chronic health condition. Both the control (n=29) and the intervention group (n=27) received diet‐related educational materials. Only the intervention group received individualized, weekly support by a Registered Dietitian Nutritionist (RDN) via telephone and videoconferencing. Diet was assessed using 4‐day food records and Nutrition Data Systems for Research (NDSR) software at weeks 0, 6, and 12. Diet quality was determined using the Healthy Eating Index (HEI‐2010). Diet quality significantly increased 9.5 points in both groups (95% CI: 3.7, 15.2) at week 6. The telenutrition group scores further increased by 9.3 points (95% CI 1.0, 17.6). No additional increase occurred at week 12 (control p‐value: 0.22; telenutrition p‐value: 0.55). A 10‐point improvement in diet quality was, on average, associated with a 0.7% reduction in body weight (95% CI: 0.4, 1.0; p‐value < 0.001). Weight loss programs delivered via videoconferencing can be effective for improving diet quality in men in health disparate areas like Appalachia.

Support or Funding Information

West Virginia Clinical and Translational Science Institute's Health Outcomes and Policy Evaluation (HOPE) Funding Opportunity with funds made available from the Claude Worthington Benedum Foundation.
The Cross‐Sectional Association between Eating Frequency and Body Composition among Adults in South China
Authors: Chen Yuan‐yuan , Xue Hong‐mei , Yin Jun , Cheng Guo
Published: November 2023

Objective

To explore whether eating frequency (EF) was associated with body composition in Chinese adults.

Methods

A total of 1017 adults (53.8% men) aged 25–65 years were included from an on‐going prospective cohort study carried out in Southwest China since 2013. Dietary data were collected by validated 24‐h dietary recalls. EF was calculated with two different methods based on the energy intake (EI) and the eating time interval: all eating occasions providing at least 50 kcal (or 210 kJ) with a minimum time interval between occasion at least 15 min or 30 min. Each EF was divided into meal frequency (MF) and snack frequency (SF). Body height and weight were measured to calculate percentage of body fat (%BF), fat mass index (FMI) and fat‐free mass index (FFMI). Multiple linear regression models were used to examine the association between EF and body composition parameters.

Results

EF and SF were positively associated with %BF, FMI (p<0.01) and negatively related to FFMI (p<0.01) after adjustment for age, occupation, personal monthly income, smoking status, alcohol, physical activity, energy intake, protein intake, fat intake and carbohydrate intake. However, MF was not associated with %BF, FMI or FFMI.

Conclusion

Our results indicate that higher EF and SF were associated with higher body fatness and lower fat‐free body mass in Chinese adults.

Support or Funding Information

Funding source: All phases of this study were supported by research grant from the National Nature Science Foundation of China (No.81472976).
Dietary effects on A2AR expression in liver and adipose tissues: A role for A2AR in protecting against inflammation and insulin resistance in obesity
Authors: Pei Ya , Cai Yuli , Li Honggui , Woo Shih‐Lung , Liu Mengyang , Huo Yuqing , Wu Chaodong
Published: November 2023

Obesity causes a wide variety of metabolic diseases including fatty liver disease and diabetes. Mechanistically, obesity‐associated inflammation has been implicated as a key factor in the development of fat deposition, insulin resistance, and metabolic dysregulation. However, the regulation of inflammation in obesity remains to be explored. As a member of the G‐protein coupled receptor families, adenosine 2A receptor (A2AR) is ant‐inflammatory. However, little is known about nutritional regulation of A2AR as it relates to insulin resistance. In the present study, the expression of A2AR in liver and adipose tissue was examined in wild type (WT) C57BL/6J mice upon feeding a high‐fat diet (HFD) or a control low‐fat diet (LFD). Also, both A2AR ‐deficient mice and WT C57BL/6J mice were fed an HFD or LFD for 12 weeks to examine the involvement of A2AR in diet‐induced inflammation and insulin resistance. Lastly, the effects of major macronutrients, i.e., glucose and palmitate, on the inflammatory responses were examined in both WT and A2AR‐deficient macrophages. Compared with LFD‐fed WT mice, HFD‐fed WT mice displayed obesity and obesity‐related inflammation in liver and adipose tissue and systemic insulin resistance. Interestingly, the levels of A2AR in both the liver and adipose tissue of HFD‐fed WT mice were increased significantly compared with LFD‐fed mice. When comparing with HFD‐fed WT mice, HFD‐fed A2AR‐deficient mice displayed an significant increase in the severity of inflammation and insulin resistance. In cultured cells, the proinflammatory responses were much enhanced in A2AR‐deficient macrophage in relative to WT cells regardless of palmitate treatment. Taken together, these results suggest that HFD feeding induces the expression of A2AR, which in turn exerts a defensive role in protecting against inflammation and insulin resistance.

Support or Funding Information

This study was support in part by NIH grants. Also, Dr. Wu is supported by an NIFA program.
Diet and MicroRNA Expression: A Systematic Review
Authors: McNaughton Sarah A , Danaher Jessica , Russell Aaron P
Published: November 2023

Background

MicroRNAs are small, non‐coding RNAs that regulate gene expression at the post‐transcriptional level. Epidemiological studies have identified association between circulating miRNAs and specific health outcomes such as cognitive function, muscle development, and cardiovascular disease. While some evidence exists to suggest that diet may modulate circulating miRNA profiles, few human studies have investigated the relationship between diet and circulating miRNA expression.

Methods

A systematic literature search was conducted to identify studies that investigated the influence of diet on miRNA expression levels in various human tissues and body fluids. MEDLINE complete, Academic Search Complete, Health Source (Academia Edition), EMBASE, Web of Science and Cochrane Central Register of Controlled Trials (CENTRAL) databases were searched for eligible articles published in English from January 1993 to October 2016.

Results

Of 3375 articles identified through database searching, 50 full‐text articles assessed for eligibility, resulting in 19 studies for inclusion. There were numerous differences in the type and duration of dietary exposures studied, the biologic source of miRNAs, and the methodologies used to quantitate miRNAs. Fourteen articles reported on miRNA responses to chronic dietary exposure (one of which was in conjunction with exercise), and five articles reported on miRNA responses to acute dietary exposures (one of which was in conjunction with exercise). Studies examined circulating miRNAs in plasma (n=5), serum (n=1), whole blood (n=2), PBMCs (n=4) and HDL (n=2). A total of 90 different circulating miRNAs were assessed with only 15 circulating miRNAs examined in two or more studies. In addition, miRNAs were examined in skeletal muscle (n=2), gastrointestinal tissues (n=2) and faeces (n=1).

Conclusions

This review is the first to examine dietary exposures and miRNA expression focusing on human studies. Data from several studies support an association between miRNAs and dietary exposure, however currently there is significant heterogeneity in the dietary exposures and miRNAs examined, and in the methodological approaches used. While the detection and stability of circulating miRNAs circulation has highlighted their potential role as biomarkers for health and disease, their nutritional regulation and consequent effect on nutrition‐related health outcomes is still in its infancy.

Support or Funding Information

SAM is supported by an National Health and Medical Research Council Career Development Fellowship, ID1104636.
The Effects of Ipriflavone, Isoflavone, and 17b‐Estradiol on Body Composition in Hamster Models of Ovariectomy
Authors: Foley Elizabeth M , Pourafshar Shirin , Navaei Negin , Akhavan Neda S , George Kelli S , Arjmandi Bahram H
Published: November 2023

Soy isoflavones have been found to have favorable effects on body composition in postmenopausal women. Ipriflavone is a synthetic isoflavone theorized to behave similarly to natural isoflavones. The purpose of this study was to compare and contrast the effects of three different treatments: isoflavone (ISO), ipriflavone (IP), and 17β‐estradiol (E2) on body composition in ovariectomized (Ovx) hamsters, and to evaluate the hamster's response to ovarian hormone deficiency. For this purpose, we used sixty‐five female Golden Syrian Hamsters, which were divided into five groups of twelve hamsters per group. All groups were Ovx except the sham‐operated (Sham) group. Thus, the groups included Sham, Ovx, Ovx+IP, Ovx+E2, and Ovx+ISO. All groups received an isoflavone‐depleted soy‐based diet, a reduced isoflavone diet (containing less than 10% of the amount usually found in soy protein isolate) except for the ISO group, which received a soy diet containing normal levels of isoflavone (2.3mg/g protein). Ipriflavone was given by gavaging (200mg/kg body weight/day) and subcutaneous injections of E2 (10mg/kg body weight) were administered on a daily basis. After 65 days of treatment, animals were exsanguinated and the bones and organs were collected for analyses. Ovariectomy was confirmed by uterine weight (0.129 ± 0.014, P< 0.0001). Hamsters behaved similarly to rats in that Ovx hamsters gained excess body fat irrespective of pair feeding. As expected, abdominal fat in Ovx hamsters in E2 and ISO was reduced significantly by 1.93 ± 0.24, and 1.44 ± 0.19, P<0.0001, respectively. Additionally, relative abdominal fat was increased in Ovx (2.47 ± 0.24, P<0.0001), but it was decreased in both E2 (1.54 ± 0.18, P<0.0001) and ISO (1.19 ± 0.15, P<0.0001) groups. The findings of this study indicate that isoflavones act similarly to estrogen in a hamster model of postmenopausal hormone deficiency, and can improve body composition thus decreasing the risk of other chronic diseases.
The synergistic anti‐obesity effect of Gelidium elegans extract and orlistat in vivo and in vitro
Authors: Choi Seo‐Yun , Park Min‐Ki , Choi Jia , Koh Eun‐Jeong , Seo Young‐Jin , Song Ji‐Hyeon , Chei Sungwoo , Hwang Ji‐Hyun , Lee Yeon‐Joo , Lee Boo‐Yong
Published: November 2023

Obesity is caused by imbalanced food intake and physical activity. A plethora of pharmaceutical agents exist to reduce body weight and associated symptoms in obese patients. However, these medications are not without adverse effects. Therefore, a natural, non‐toxic and cost‐effective food ingredient, such as Gelidium elegans, warrants further consideration in the anti‐obesity arena. Gelidium elegans is a species of red algae that mostly grows in the northeastern Sea of Asia. In this study, we investigated the molecular mechanism of adipogenesis inhibition induced by the ethanol extract of Gelidium elegans on 3T3‐L1 adipocytes and high fat diet mice. We found that exposure to 12.5 and 25 μg/mL concentrations of the Gelidium elegans ethanol extract inhibited adipocyte differentiation through the regulation of PPARγ, C/EBPα, and FABP4 expression. Moreover, we found that exposure to the 25 mg/mL concentration of the Gelidium elegans ethanol extract caused a three‐fold increase in the expression of genes related to brown adipocyte differentiation (such as UCP‐1 and PRDM16) compared with the control group. To elucidate the synergistic anti‐obesity effects of Gelidium elegans, male ICR mice were fed on high fat diets and with or without Gelidium elegans extract (50mg/kg and 200mg/kg) and orlistat (20mg/kg) intervention for 8 weeks. The body weight increase and weight significantly reduced by the diets containing Gelidium elegans extract (200mg/kg) and orlistat + Gelidium elegans extract (50mg/kg). Serum concentration of triglycerides (TG) and glucose were decreased by Gelidium elegans extract and orlistat. Also, we found that Gelidium elegans (200mg/kg/day) prevented hyperglycemia. Our findings suggest that Gelidium elegans ethanol extract enhances energy expenditure and suppresses adipocyte differentiation. Gelidium elegans ethanol extract may be a safe, effective and economical food grade ingredient for obese patients.
Synthetic Lethality of K‐Ras Mutant Human Colorectal Cancer Cells by Phytochemical Curcumin and FDA‐Approved Targeted Drug Regorafenib
Authors: Su Chun‐Li , Wu Chi‐Shiuan
Published: November 2023

Synthetic lethality refers to the interaction between two co‐essential genes such that inhibiting the function of either gene separately results in cell survival, but inhibiting the function of both genes results in cell death. Targeting synthetic lethal interactions may spare normal cells while selectively killing cancer cells. Curcumin, a major yellow pigment and spice in turmeric and curry, has been demonstrated to have anticarcinogenic effect in vitro, in vivo, and in human clinical trials. Colorectal cancer (CRC) is the third most commonly diagnosed cancer and the forth cause of cancer death worldwide. Mutation of K‐Ras, a Ras superfamily of protein which regulates cell proliferation and survival, has been shown in 35–45% of CRC. Regorafenib is an oral inhibitor that targets multi‐kinase activity (eg. Raf) which involves in tumor angiogenesis, oncogenesis, and tumor microenvironment. Recently, Regorafenib has been approved by the US FDA to treat patients with CRC despite the genotype of K‐Ras after failure of using standard therapies. However, administration of Regorafenib only improved overall survival by nearly 1.4 months in patients with treatment‐refractory metastatic CRC. Here we reveal that curcumin significantly enhanced the cytotoxicity of human CRC HCT 116 cells (K‐Ras mutant) to Regorafenib to a greater extent than that of human CRC HT‐29 cells (K‐Ras wild‐type), producing an additivity or synergy effect on HCT 116 cells and causing an antagonism effect on HT‐29 cells. Flow cytometric analysis displayed that the addition of curcumin elevated the percentages of HCT 116 cells at the sub‐G1 phase, representing induction of apoptosis, as well as greatly increased the cells with acidic vesicular organelles, representing the formation of autolysosomes at the later stage of autophagic flux. Expression of cleaved caspase 3 (at the later stage of apoptosis) and LC3‐II (at the early stage of autophagic process) using Western blot analysis confirmed the induction of apoptosis and autophagy of the HCT 116 cells. No induction of apoptosis or autophagy was observed on HT‐29 cells in response to curcumin, Regorafenib, or combination of these two compounds. It is noteworthy that addition of MEK specific inhibitor (U0126) not only induced apoptosis on Regorafenib‐treated HT‐29 cells, but also behaved like curcumin to enhance Regorafenib‐induced cytotoxicity, apoptosis, and autophagy on HCT 116 cells. Our data suggest that the addition of curcumin may target one more gene other than mutant K‐Ras and enhanced Regorafenib‐induced cytotoxicity (synthetic lethality) on CRC HCT 116 cells, indicating a possible role of curcumin on Regorafenib‐treated K‐Ras mutant CRC.

Support or Funding Information

(Supported in part by the Ministry of Science and Technology, Taiwan, No. MOST 104‐2320‐B‐003‐007 and National Taiwan Normal University, Taiwan, No. 105T0700).
Dietary delta‐tocotrienol favors abundance and diversity of beneficial microbiomes in obese male mice
Authors: Shen ChwanLi , Kottapalli Rao , Tomison Michael D , Koboziev Iurii , Web Cynthia Reinoso , Ramalingam Latha , Moustaid‐Moussa Naima , Kaur Gurvinder , Dufour Jannette , Chung Eunhee , Mo Huanbiao , Grisham Matthew Reinoso
Published: November 2023

Obesity and its associated metabolic disorders are a world‐wide health problem. Recent reports postulated that distinct gut microbiota alterations were observed in obese/diabetic subjects. Modulating gut microbiota through bioactive compounds could be a potential therapeutic option. Our previous study has demonstrated that tocotrienols (TT) exert beneficial effects on glucose homeostasis. Therefore, the goal of this study was to further characterize TT‐driven shifts in the cecal microbiome in obese mice with insulin resistance. Twenty male C57BL/6J mice (6‐week‐old) were divided into 2 groups: high‐fat diet (HFD, 60% energy from fat) and HFD+800 mg TT/kg diet (TT800) for 14 weeks. TT is a mixture of 90% delta‐TT and 10% gamma‐TT. To determine the effects of TT on glucose homeostasis and insulin resistance, glucose tolerance and insulin tolerance tests were performed. For microbiome determination, cecal content was collected, DNA was extracted, and 16S rRNA gene metagenome was sequenced. Compared to the HFD group, TT supplementation improved glucose homeostasis as measured by both glucose tolerance test (369.3±22.6 and 243.6±38.9 mg/dL for HFD and TT800, respectively) and insulin tolerance test (relative to time zero: 53.1% and 44.4% for HFD and TT800, respectively). Relative to the HFD diet, dietary TT supplementation increased the Bacteroidetes/Firmicutes ratio in mouse cecum. The number of bacteria which belong to Clostridiales order, especially the Oscillospira genus (Firmicutes phylum) was decreased by 2 fold, whereas the number of S24–7 family members (Bacteroidetes phylum) was significantly increased. Representation of the Akkermansia genus (mucolytic bacteria of Verrucomicrobia phylum) was also increased significantly in the cecal feces of animals supplemented with TT. This study demonstrates that the beneficial effect of TT on glucose homeostasis may be mediated in part through increasing the abundance of beneficial gut microbiome in obese male mice with insulin resistance.

Support or Funding Information

American River Nutrition, Inc., Hadley, MA
Protective effect of anthocyanin on alcohol‐induced liver fibrosis is due to the regulation on AMPK/mTOR/autophagy pathway and energy status
Authors: Yang Lili , Wan Ting , Wang Sufan , Ye Mingtong , Pei Lei , Jiang Rui , Qiu Yun
Published: November 2023

Liver fibrosis is an advanced stage of liver damage by alcohol. We hypothesize that anthocyanin can protect alcohol induced liver fibrosis. We fed mice with high fat diet with ehanol in dringking water to induce liver fibrosis. Anthocyanin was supplied by gavage every day. We found that 12 wks feeding of high fat diet and alcohol induced lipid accumulation and increased expression of collagen α, α‐SMA, TGF‐β, and TIMP‐1 and −2, while anthocyanin supplement inhibited the increase of these parameters. In addition, we found that high fat and ethanol feeding induced increase of liver oxidative stress, increased activation of AMPK pathway, and increased autophagy, while anthocyanin supplement inhibited these effects in liver. Moreover, we found that supplement of anthocyanin reversed energy deficiency induced by high fat and ethanol feeding, including the levels of ATP, ADP, AMP, NAD+, and NMN in the liver. In conclusion, the protective effect of anthocyanin on ethanol induced liver fibrosis is due to the regulation on AMPK/mTOR/autophagy pathway, which finally regulates the energy supply in the liver.

Support or Funding Information

National Natural Science Funding (81370528, 81573142)(Yang, L), Provincial Natural Science Funding of Guangdong (2015A030313078) (Yang, L.)
Pterostilbene inhibits adipocyte differentiation by targeting CHOP10 in 3T3‐L1
Authors: Kim Kui‐Jin , Seo Young‐Jin , Koh Eun‐Jeong , Choi Jia , Hwang Ji‐Hyun , Lee Yeon‐Joo , Song Ji‐Hyeon , Chei Sungwoo , Choi Seo‐Yun , Park Min‐Ki , Lee Boo‐Yong
Published: November 2023

Pterostilbene has been shown that attenuates adipogenesis through the regulation of adipogenesis markers. However, it has not been shown whether pterostilbene affects the mitotic clonal expansion (MCE) during adipogenesis. We therefore aimed to demonstrate the detail mechanism of pterostilbene on adipogenesis of 3T3‐L1. Consistent with previous report, our result showed pterostilbene suppressed the expression of C/EBPα, PPARγ and aP2. In addition, we observed that pterostilbene increased the MCE‐associated proteins CHOP10 and subsequently inhibit the progression of next stage of adipognesis. These results indicated that pterostilbene may repress adipocyte differentiation through the activation of CHOP10 expression prior to entering into the MCE. Together, we demonstrated that pterostilbene suppresses the initiation of MCE via retaining of CHOP10 expression during adipocyte differentiation of 3T3‐L1.
Flavonol Kaempferol Improves Glucose Homeostasis via Suppressing Hepatic Glucose Production and Enhancing Insulin sensitivity in Diabetic Mice
Authors: Moore William , Alkhalidy Hana , Zhou Kequan , Liu Dongmin
Published: November 2023

In type 2 diabetes, the increase in the activity of the key enzymes that control glycogenolysis and gluconeogenesis in the liver causes an increase in hepatic glucose production, which is the main contributor to the development of fasting hyperglycemia. Here, we investigated the anti‐diabetic potential of flavonol kaempferol. Oral administration of kaempferol (50 mg/kg) significantly improved fasting blood glucose levels, glucose intolerance, and insulin sensitivity in high‐fat diet‐induced obese insulin resistant mice. These beneficial effects were associated with improved pyruvate tolerance and reduced hepatic glucose production. Consistently, kaempferol treatment increased Akt and hexokinase activity but decreased pyruvate carboxylase activity in the liver of obese mice. Kaempferol also enhanced whole body insulin sensitivity without altering body weight gain, food consumption, or adiposity of obese mice. These kaempferol actions were also demonstrated in STZ‐induced insulin‐deficient diabetic mice. In vitro, kaempferol increases glucose uptake of primary human skeletal muscle cells while reducing gluconeogenesis in HepG2 cells. These findings suggest that kaempferol may be a naturally occurring anti‐diabetic compound by improving insulin sensitivity and suppressing glucose production.

Support or Funding Information

The work was supported by grants from NCCIH of NIH (1R01AT007077, 1R01AT007566).
Use of Spot Urine Caffeine and Caffeine Metabolite Concentrations for Distinguishing a Recommended Upper Limit of Caffeine Intake
Authors: Rybak Michael E. , Sternberg Maya R. , Pao Ching‐I
Published: November 2023

Urine excretion of caffeine and select caffeine metabolites is common in the US population and associated with caffeine intake. In particular, caffeine metabolites resulting from metabolism via paraxanthine and/or theophylline show promise as potential caffeine intake biomarkers. The 2015–2020 Dietary Guidelines for Americans state that up to 400 mg/day of caffeine can be incorporated into a healthy eating style. In this study we performed receiver operating characteristic (ROC) analysis of unweighted data from the NHANES 2009–2010 to determine optimal cutoffs for spot urine caffeine and 14 caffeine metabolites that would maximize the correct classification of individuals with 24‐h caffeine intake >400 mg/d vs. ≤400 mg/d (from diet and supplements). We limited our study sample to subjects ≥12 y of age and excluded individuals taking prescription medications known to interfere with caffeine metabolism. For each analyte we calculated an unweighted ROC estimate for the optimal cutoff concentration, as well as estimates of sensitivity, specificity, area under the ROC curve (AUC), and an overall rate of correct classification. We calculated these estimates for the total study population, as well as stratified by age, sex and race‐ethnicity. Using our ROC estimates for optimal cutoff concentrations, we observed the highest overall rate of correct classification (72.2%) with 1,3‐dimethyluric acid (13U) (cutoff: 12.4 μmol/L; sensitivity: 69.7%; specificity: 72.2%). In addition to 13U, we also saw correct classification rates >70% for 5‐acetylamino‐6‐amino‐3‐methyluracil (AAMU) (cutoff: 98.4 μmol/L; sensitivity: 69.0%; specificity: 71.4%) and 1‐methyluric acid (1U) (cutoff: 98.1 μmol/L; sensitivity: 71.7%; specificity: 70.8%). The greatest AUC was observed for 1U (0.776; 95% CI: 0.740–0.811), with similarly high AUCs observed for AAMU (0.763; 95% CI: 0.726–0.800), 13U (0.776; 95% CI: 0.726–0.799), and 1‐methylxanthine (1X) (0.768; 95% CI: 0.733–0.804) which had correct classification rate of 68.5% (cutoff: 45.3 μmol/L; sensitivity: 0.724; specificity: 0.682). Theobromine (cutoff: 16.3 μmol/L; sensitivity: 69.7%; specificity: 49.4%) had the lowest overall rate of correct classification (50.9%), as well as the lowest AUC (0.603; 95% CI: 0.563–0.642). Depending on the analyte, we noted that the ROC estimate for optimal cutoff concentration could vary by age, sex, or race‐ethnicity. We believe that our study is the first report of using ROC analysis to determine cutoff values for spot urine caffeine and caffeine metabolite concentrations to classify individuals based on their caffeine intake, and that this approach holds promise as a means of identifying individuals whose recent caffeine intake may have exceeded a recommended upper limit of 400 mg/day.