Yes / Obesity research priority setting, if conducted to a high standard, can help promote policy-relevant and efficient research. Therefore, there is a need to identify existing research priority setting studies conducted in the topic area of obesity and to determine the extent to which they followed good practice principles for research priority setting. Studies examining research priority setting in obesity were identified through searching the MEDLINE, PBSC, CINAHL, PsycINFO databases and the grey literature. The nine common themes of good practice in research priority setting were used as a methodological framework to evaluate the processes of the included studies. These were context, use of a comprehensive approach, inclusiveness, information gathering, planning for implementation, criteria, methods for deciding on priorities, evaluation and transparency. Thirteen articles reporting research prioritisation exercises conducted in different areas of obesity research were included. All studies reported engaging with various stakeholders such as policy makers, researchers and healthcare professionals. Public involvement was included in six studies. Methods of research prioritisation commonly included both Delphi and nominal group techniques and surveys. None of the 13 studies fulfilled all nine of the good practice criteria for research priority setting, with the most common limitations including not using a comprehensive approach and lack of inclusivity and evaluating on their processes. There is a need for research priority setting studies in obesity to involve the public and to evaluate their exercises to ensure they are of high quality. / National Institute for Health Research (NIHR) under its Applied Research Collaboration (ARC) Yorkshire and Humber in the form of Ph.D. funding to HI [NIHR200166], the UK Prevention Research Partnership (UKPRP) in the form of funding to JW and RM [MR/S037527/1], the NIHR Clinical Research Network in the form of funding to JW, and the NIHR ARC Yorkshire and Humber in the form of funding to RM

Die kumulative Habilitationsschrift untersucht das Harnblasengewebe, das Serumproteom sowie das Proteom der HDL-Partikel, humane Aorten-Endothelzellen und das Darm-Mikrobiom im Kontext der Adipositas und unter dem Einfluss bariatrisch-chirurgischer Interventionen. Im Fokus wissenschaftlichen Interesses standen die Identifikation von Biomarkern zur Abschätzung und zum Monitoring von Herz-Kreislauf-Erkrankungen, chronischer Entzündungsprozesse sowie die Aufklärung von Anpassungsmechanismen einer Harnblasendysfunktion und die Untersuchung des mikrobiellen Ökosystems unter dem Einfluss der Adipositas. Die wissenschaftlichen Beiträge basieren auf Zellkultur- und tierexperimentellen Studien sowie auf Humananalysen. Die Global- bzw. Target-Proteomik-Studien erfolgten im Sinne eines Bottom-up-Ansatzes unter Anwendung von Gel-basierenden und Gel-freien Proteintrennverfahren und nachfolgend massenspektrometrischer Analyse. Durch die Anwendung von variablen Proteomik-Plattformen konnten Adipositas-assoziierte Risikoparameter im Serum zur Identifikation von Komorbiditäten ermittelt und validiert werden. In der Konsequenz dieser Resultate wurde ein MRM-Assay erarbeitet. Die Untersuchungen von HDL-Partikeln zeigten eine hohe interindividuelle Varianz des HDL-Proteoms und eine Vielzahl bisher unbekannter Proteine wurden dem HDL-Proteom und der NO-assoziierten HDL-Funktion zugeordnet. Die Proteomik deckte im besonderen Maße die Adipositas-assoziierte Pathophysiologie der Harnblasendysfunktion auf. Weiterführende Studien des Harnblasen-Proteoms im Tiermodell belegen die positive Wirkung einer bariatrischen Intervention. Die Untersuchung des Proteoms der Darmbakterien belegt den Nutzen der Proteomik in der Aufklärung der mikrobiellen Diversität und des damit verbundenen spezifischen bakteriellen Stoffwechsels sowohl in Stuhlproben als auch in der Darmschleimhaut. Die Markierung von Stickstoffquellen in der Nahrung mittels 15N-Isotopen gibt in vivo entscheidende Hinweise auf den Stoffwechsel der Bakterien und des Wirtes bzw. deren Interaktionen.

Die kumulative Habilitationsschrift untersucht das Harnblasengewebe, das Serumproteom sowie das Proteom der HDL-Partikel, humane Aorten-Endothelzellen und das Darm-Mikrobiom im Kontext der Adipositas und unter dem Einfluss bariatrisch-chirurgischer Interventionen. Im Fokus wissenschaftlichen Interesses standen die Identifikation von Biomarkern zur Abschätzung und zum Monitoring von Herz-Kreislauf-Erkrankungen, chronischer Entzündungsprozesse sowie die Aufklärung von Anpassungsmechanismen einer Harnblasendysfunktion und die Untersuchung des mikrobiellen Ökosystems unter dem Einfluss der Adipositas. Die wissenschaftlichen Beiträge basieren auf Zellkultur- und tierexperimentellen Studien sowie auf Humananalysen. Die Global- bzw. Target-Proteomik-Studien erfolgten im Sinne eines Bottom-up-Ansatzes unter Anwendung von Gel-basierenden und Gel-freien Proteintrennverfahren und nachfolgend massenspektrometrischer Analyse. Durch die Anwendung von variablen Proteomik-Plattformen konnten Adipositas-assoziierte Risikoparameter im Serum zur Identifikation von Komorbiditäten ermittelt und validiert werden. In der Konsequenz dieser Resultate wurde ein MRM-Assay erarbeitet. Die Untersuchungen von HDL-Partikeln zeigten eine hohe interindividuelle Varianz des HDL-Proteoms und eine Vielzahl bisher unbekannter Proteine wurden dem HDL-Proteom und der NO-assoziierten HDL-Funktion zugeordnet. Die Proteomik deckte im besonderen Maße die Adipositas-assoziierte Pathophysiologie der Harnblasendysfunktion auf. Weiterführende Studien des Harnblasen-Proteoms im Tiermodell belegen die positive Wirkung einer bariatrischen Intervention. Die Untersuchung des Proteoms der Darmbakterien belegt den Nutzen der Proteomik in der Aufklärung der mikrobiellen Diversität und des damit verbundenen spezifischen bakteriellen Stoffwechsels sowohl in Stuhlproben als auch in der Darmschleimhaut. Die Markierung von Stickstoffquellen in der Nahrung mittels 15N-Isotopen gibt in vivo entscheidende Hinweise auf den Stoffwechsel der Bakterien und des Wirtes bzw. deren Interaktionen.

Yes / British South Asians have a higher prevalence of overweight and obesity than the wider population. Bradford (UK), with its high Pakistani presence and levels of economic deprivation, has exceptionally high instances, especially in deprived areas where many Pakistanis reside. British Pakistani women in Bradford are more likely to be overweight and obese. There is uncertainty on how these women can be aided to manage their weight. Therefore, the objective of this study was to explore the obesity concerns of Pakistani women living in deprived inner-city areas of Bradford. Three focus groups interviews were carried out with 23 Pakistani women living in deprived areas of Bradford. Data were analysed thematically. This exploratory study identified a wide range of concerns that women had around managing their weight. Participants disclosed distrust in information given around medication, conflicting dietary information and reported low levels of trust in women-only organized physical activities. Cultural barriers were identified, which included the gender role of the woman, the lack of culturally appropriate dietary advice, cultural misunderstandings of what constitutes a healthy diet and healthy weight, the lack of culturally suitable exercise facilities and conforming to family and community expectations. Other concerns were language barriers around a lack of understanding, the inability to read Urdu and reliance on others to translate information. These findings have implications for researchers, local authorities, policy makers and others with an interest in reducing the rates of obesity in this population. Recommendations include training health practitioners to be culturally aware of the diet and eating practices of this community, exploring different ways to support socially isolated women to be more physically active at home, addressing physical activity and diet misconceptions and designing obesity management information materials appropriate for a range of literacy levels. Public contributors were involved in the development of the interview guide and design of the research. A pilot focus group with participants not included in the present paper was used to help test and refine the focus group questions. Interview transcripts were member checked by participants, and participants assisted with data analysis. / UKPRP. Grant Number: MR/S037527/1 NIHR. Grant Number: NIHR200166

Introduction: British Pakistani women have exceptionally high rates of obesity and yet are seldom heard in a research priority setting concerning weight management. The objectives of this study were (i) to ascertain what multisectoral professionals perceive to be the most pressing unmet obesity needs or topic areas that need more research in relation to Pakistani women living in deprived areas of Bradford and (ii) to determine the top 10 obesity health priorities for this group to develop an obesity research agenda. Methods: A two‐step process was adopted using the following: (i) a survey of a wide range of multisectoral professional stakeholders (n= 159) and (ii) a ranking exercise involving Pakistani women living in deprived areas of Bradford (n= 32) to select and prioritize their top 10 obesity health concerns and unmet needs from a list of 31statements identified in the survey and previous research. Survey data were analysed using inductive content analysis and themes were identified. Themes were translated into statements to be ranked by Pakistani women. The ranking exercise was conducted by telephone either via voice or video call. Data were analysed using a reverse scoring system. Results: Survey responses were grouped into statements reflecting the following three categories: education needs; healthy behaviour barriers and mental well‐being. The highest rankings were given by Pakistani women to statements on mental health and the need for education. The top 10 prioritized statements were developed with members of the public into an obesity research agenda that reflected the target population. Conclusion: Actively engaging British Pakistani women in setting research priorities provided a unique opportunity to understand the key areas they think are important for future research. The culminating research agenda can be used by researchers to advance the field of obesity research in Pakistani communities, thus producing research outputs that are relevant to and have impact in this population. Patient or Public Contribution: Participants in the ranking exercise collected data. Public contributors were involved in developing the prioritized statements into are search agenda. / NIHR, Grant/Award Number: NIHR200166;UKPRP, Grant/Award Number:MR/S037527/1

Yes / Participation of community stakeholders in health research priority setting is an emerging trend. Despite this, the involvement of marginalised groups in research prioritisation is limited and where they are involved, sample sizes are small, where individuals are merely consulted with, rather than coproducing the research agenda. Without addressing power dynamics inherent in research prioritisation with marginalised groups, their engagement in the research process can be tokenistic and the resulting research agenda unreflective of their needs. This article, therefore, aims to generate knowledge on how feminist participatory action research was used to co-produce an obesity research agenda with British Pakistani women, a seldom heard population, living in deprived areas. The methodology enabled Pakistani women to be involved in all stages of the project, culminating in the co-production of an obesity research agenda that accurately reflects their unmet needs. Women’s engagement in the project led to their increased confidence, the formation of relationships that lasted beyond the research project, improvements to their lifestyles, and engagement in further research. Feminist participatory action research may be used by researchers as a guiding methodology due to its ability to improve women’s lives and develop research agendas for women’s health. / National Institute for Health Research (NIHR) under its Applied Research Collaboration (ARC) Yorkshire and Humber [NIHR200166], the UK Prevention Research Partnership (UKPRP) - [MR/S037527/1], the NIHR Clinical Research Network, NIHR ARC Yorkshire and Humber / Research Development Fund Publication Prize Award winner, Jul 2023.

Indiana University-Purdue University Indianapolis (IUPUI) / Obesity is a substantial threat to the health of over a third of adults in the United States. Some evidence suggests that food attentional bias, or the tendency to automatically direct attention toward food-related stimuli in the environment, may contribute to the development of obesity in susceptible individuals. This study hypothesized that (1) food attentional bias would be positively associated with adiposity, (2) food attentional bias would be positively associated with energy intake and external eating, and (3) energy intake and external eating would partially mediate the association between food attentional bias and adiposity. Data were collected from a sample of 120 undergraduate students. Three measures of food attentional bias were obtained: reaction time bias obtained from a visual dot-probe task and direction bias and duration bias obtained from eye tracking. Adiposity indices of body mass index (kg/m2) and body fat percent were measured using standard medical devices. Data were obtained for two mediators: 1) energy intake was assessed by web-based automated 24-hour dietary recall and 2) external eating was assessed using the External Eating Subscale of the Dutch Eating Behavior Questionnaire. Separate linear regression models examining the association between each measure of food attentional bias with each measure of adiposity (adjusted for age, sex, race/ethnicity, and subjective hunger) indicated no associations. Similarly, linear regression analyses revealed no associations between measures of food attentional bias and energy intake or external eating. Models testing for statistical mediation demonstrated that energy intake and external eating were not significant mediators. However, mediation analyses demonstrated a significant overall effect and direct effect between direction bias and BMI in a reduced sample used to test for energy intake as a mediator, suggesting the presence of an association which may not have been detected in the larger sample due to methodological issues, measurement error, or type I error. Despite the overall null results, these findings, in conjunction with previous studies on food attentional biases and adiposity, highlight the need for future investigations examining prospective associations between food attentional bias and adiposity.

Indiana University-Purdue University Indianapolis (IUPUI) / Type 2 diabetes manifests from peripheral insulin resistance and a loss of functional beta cell mass due to decreased beta cell function, survival, and/or proliferation. Beta cell stressors impair each of these factors by activating stress response mechanisms, including endoplasmic reticulum (ER) stress. The glucolipotoxic environment of the diabetic milieu also activates a stress response in beta cells, resulting in death and decreased survival. Whereas the cell cycle machinery (comprised of cyclins, kinases, and inhibitors) regulates proliferation, its involvement during beta cell stress in the development of diabetes is not well understood. Interestingly, in a screen of multiple cell cycle inhibitors, p21 was dramatically upregulated in INS-1-derived 832/13 cells and rodent islets by two independent pharmacologic inducers of beta cell stress - dexamethasone and thapsigargin. In addition, glucolipotoxic stress mimicking the diabetic milieu also induced p21. To further investigate p21’s role in the beta cell, p21 was adenovirally overexpressed in 832/13 cells and rat islets. As expected given p21’s role as a cell cycle inhibitor, p21 overexpression decreased [3H]-thymidine incorporation and blocked the G1/S and G2/M transitions as quantified by flow cytometry. Interestingly, p21 overexpression activated apoptosis, demonstrated by increased annexin- and propidium iodide-double-positive cells and cleaved caspase-3 protein. p21-mediated caspase-3 cleavage was inhibited by either overexpression of the anti-apoptotic mitochondrial protein Bcl-2 or siRNA-mediated suppression of the pro-apoptotic proteins Bax and Bak. Therefore, the intrinsic apoptotic pathway is central for p21-mediated cell death. Like glucolipotoxicity, p21 overexpression inhibited the insulin cell survival signaling pathway while also impairing glucose-stimulated insulin secretion, an index of beta cell function. Under both conditions, phosphorylation of insulin receptor substrate-1, Akt, and Forkhead box protein-O1 was reduced. p21 overexpression increased Bim and c-Jun N-terminal Kinase, however, siRNA-mediated reduction or inhibition of either protein, respectively, did not alter p21-mediated cell death. Importantly, islets of p21-knockout mice treated with the ER stress inducer thapsigargin displayed a blunted apoptotic response. In summary, our findings indicate that p21 decreases proliferation, activates apoptosis, and impairs beta cell function, thus being a potential target to inhibit for the protection of functional beta cell mass.