• Acylated apelin-13 amide analogues exhibit enzyme resistance and prolonged insulin releasing, glucose lowering and anorexic properties

      O'Harte, Finbarr P M; Parthsarathy, Vadivel; Hogg, Christopher; Flatt, Peter R; University of Ulster (Elsevier, 2017-10-04)
      The adipokine, apelin has many biological functions but its activity is curtailed by rapid plasma degradation. Fatty acid derived apelin analogues represent a new and exciting avenue for the treatment of obesity-diabetes. This study explores four novel fatty acid modified apelin-13 analogues, namely, Lys8GluPAL)apelin-13 amide, pGlu(Lys8GluPAL)apelin-13 amide, Lys8GluPAL(Tyr13)apelin-13 and Lys8GluPAL(Val13)apelin-13. Fatty acid modification extended the half-life of native apelin-13 to >24 h in vitro. pGlu(Lys8GluPAL)apelin-13 amide was the most potent insulinotropic analogue in BRIN-BD11 cells and isolated islets with maximal stimulatory effects of up to 2.7-fold (p < .001). (Lys8GluPAL)apelin-13 amide (1.9-fold) and Lys8GluPAL(Tyr13)apelin-13 (1.7-fold) were less effective, whereas Lys8GluPAL(Val13)apelin-13 had an inhibitory effect on insulin secretion. Similarly, pGlu(Lys8GluPAL)apelin-13 amide was most potent in increasing beta-cell intracellular Ca2+ concentrations (1.8-fold, p < .001) and increasing glucose uptake in 3T3-L1 adipocytes (2.3-fold, p < .01). Persistent biological action was observed with both pGlu(Lys8GluPAL)apelin-13 amide and (Lys8GluPAL)apelin-13 amide significantly reducing blood glucose (39-43%, p < .01) and enhancing insulin secretion (43-56%, p < .001) during glucose tolerance tests in diet-induced obese mice. pGlu(Lys8GluPAL)apelin-13 amide and (Lys8GluPAL)apelin-13 amide also inhibited feeding (28-40%, p < .001), whereas Lys8GluPAL(Val13)apelin-13 increased food intake (8%, p < .05) in mice. These data indicate that novel enzymatically stable analogues of apelin-13 may be suitable for future development as therapeutic agents for obesity-diabetes.
    • Beneficial long-term antidiabetic actions of N- and C-terminally modified analogues of apelin-13 in diet-induced obese diabetic mice

      Parthsarathy, Vadivel; Hogg, Christopher; Flatt, Peter R.; O'Harte, Finbarr P. M.; University of Ulster; School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK; School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK; School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK; School of Biomedical Sciences, SAAD Centre for Pharmacy and Diabetes; University of Ulster; Coleraine Northern Ireland, UK (Wiley, 2017-07-20)
      To investigate the chronic effects of twice-daily administration of stable apelin analogues, apelin-13 amide and pyroglutamyl (pGlu) apelin-13 amide, on metabolic variables in glucose-intolerant and insulin-resistant diet-induced obese mice fed a high-fat diet for 150 days. Groups of mice received twice-daily (9 am and 5 pm) injections of saline vehicle, apelin-13 amide, (pGlu)apelin-13 amide or exendin-4(1-39) for 28 days (all at 25 nmol/kg). Energy intake, body weight, non-fasting blood glucose, plasma insulin, glucose tolerance, metabolic response to feeding and insulin sensitivity, together with pancreatic hormone content and biochemical variables such as lipids and total GLP-1 were monitored. Dual-energy X-ray absorptiometry analysis and indirect calorimetry were also performed. Administration of apelin-13 amide, (pGlu)apelin-13 amide or exendin-4 significantly decreased body weight, food intake and blood glucose and increased plasma insulin compared with high-fat-fed saline-treated controls (P < .05 and P < .001), Additionally, all peptide-treated groups exhibited improved glucose tolerance (oral and intraperitoneal), metabolic responses to feeding and associated insulin secretion. (pGlu)apelin-13 amide also significantly improved glycated haemoglobin and insulin sensitivity after 28 days. Both (pGlu)apelin-13 amide and exendin-4 increased bone mineral content and decreased respiratory exchange ratio, whereas only (pGlu)apelin-13 amide increased energy expenditure. All treatment groups displayed reduced circulating triglycerides and increased glucagon-like peptide-1 concentrations, although only (pGlu)apelin-13 amide significantly reduced LDL cholesterol and total body fat, and increased pancreatic insulin content. These data indicate the therapeutic potential of stable apelin-13 analogues, with effects equivalent to or better than those of exendin-4.
    • Examining factors of engagement wth digital interventions for weight management: Rapid review

      Sharpe, Emma; Karasouli, Eleni; Meyer, Caroline; University of Derby; University of Warwick (JMIR Publications, 2017-10-23)
      Background: Digital interventions for weight management provide a unique opportunity to target daily lifestyle choices and eating behaviors over a sustained period of time. However, recent evidence has demonstrated a lack of user engagement with digital health interventions, impacting on the levels of intervention effectiveness. Thus, it is critical to identify the factors that may facilitate user engagement with digital health interventions to encourage behavior change and weight management. Objective: The aim of this study was to identify and synthesize the available evidence to gain insights about users’ perspectives on factors that affect engagement with digital interventions for weight management. Methods: A rapid review methodology was adopted. The search strategy was executed in the following databases: Web of Science, PsycINFO, and PubMed. Studies were eligible for inclusion if they investigated users’ engagement with a digital weight management intervention and were published from 2000 onwards. A narrative synthesis of data was performed on all included studies. Results: A total of 11 studies were included in the review. The studies were qualitative, mixed-methods, or randomized controlled trials. Some of the studies explored features influencing engagement when using a Web-based digital intervention, others specifically explored engagement when accessing a mobile phone app, and some looked at engagement after text message (short message service, SMS) reminders. Factors influencing engagement with digital weight management interventions were found to be both user-related (eg, perceived health benefits) and digital intervention–related (eg, ease of use and the provision of personalized information). Conclusions: The findings highlight the importance of incorporating user perspectives during the digital intervention development process to encourage engagement. The review contributes to our understanding of what facilitates user engagement and points toward a coproduction approach for developing digital interventions for weight management. Particularly, it highlights the importance of thinking about user-related and digital tool–related factors from the very early stages of the intervention development process.
    • The impact of self-criticism and self-reassurance on weight-related affect and well-being in participants of a commercial weight management programme.

      Duarte, Cristiana; Stubbs, James; Pinto-Gouveia, José; Matos, Marcela; Gale, Corinne; Morris, Liam; Gilbert, Paul; University of Coimbra; University of Leeds; Slimming World; et al. (Karger, 2017-04-04)
      Objective: Certain psychological and emotional factors can undermine attempts at weight management. Previously we have found that shame and self-criticism were significantly associated with disinhibition and perceived hunger in 2,236 participants of a weight management programme. This effect was fully mediated through weight-related negative affect. The present study examined the impact of self-criticism and self-reassurance on well-being and whether it was mediated by weight-related affect in the same population. Methods: Participants completed an online survey of measures of self-criticism and self-reassurance, and negative and positive affect associated with weight and well-being. Results: Path analysis suggested that self-criticism was significantly associated with decreased well-being, both directly and indirectly, mediated by increased negative and decreased positive weight-related affect. Self-reassurance had a stronger association with increased well-being by predicting lower negative and increased positive weight-related affect. All effects were significant at p < 0.001. Conclusion: Self-criticism and self-reassurance were related to well-being in participants attempting to manage their weight, both directly and through their impact on weight-related affect. The positive association between self-reassurance and well-being was stronger than the negative association between self-criticism and well-being. Supporting the development of self-reassuring competencies in weight management programmes may improve weight-related affect and well-being.
    • The impact of shame, self-criticism and social rank on eating behaviours in overweight and obese women participating in a weight management programme

      Duarte, Cristiana; Matos, Marcela; Stubbs, James; Gale, Corinne; Morris, Liam; Gouveia, Jose Pinto; Gilbert, Paul; University of Coimbra; University of Derby; Slimming World; et al. (Public Library of Science (PLOS), 2017-01-20)
      Recent research has suggested that obesity is a stigmatised condition. Concerns with personal inferiority (social rank), shame and self-criticism may impact on weight management behaviours. The current study examined associations between social comparison (shame, self-criticism), negative affect and eating behaviours in women attending a community based weight management programme focused on behaviour change. 2,236 participants of the programme completed an online survey using measures of shame, self-criticism, social comparison, and weight-related affect, which were adapted to specifically address eating behaviour, weight and body shape perceptions. Correlation analyses showed that shame, self-criticism and social comparison were associated with negative affect. All of these variables were related to eating regulation and weight control (p < 0.001). Path analysis revealed that the association of shame, hated-self, and low self-reassurance on disinhibition and susceptibility to hunger was fully mediated by weight-related negative affect, even when controlling for the effect of depressive symptoms (p < 0.050 to p < 0.010). In addition, feelings of inadequacy and unfavourable social comparisons were associated with higher disinhibition and susceptibility to hunger, partially mediated through weight-related negative affect (p = 0.001). These variables were negatively associated with extent of weight loss during programme attendance prior to the survey, while self-reassurance and positive social comparisons were positively associated with the extent of weight loss prior to the survey (p < .050). Shame, self-criticism, and perceptions of inferiority may play a significant role in self-regulation of eating behaviour in overweight people trying to manage their weight.
    • A qualitative study of the understanding and use of ‘compassion focused coping strategies’ in people who suffer from serious weight difficulties.

      Gilbert, Jean; Stubbs, James; Gale, Corinne; Gilbert, Paul; Dunk, Laura; Thomson, Louise; Derbyshire Healthcare NHS Trust; Slimming World; University of Derby; University of Nottingham (Biomed Central, 2014-11-11)
      Abstract Background The physical and psychological health problems associated with obesity are now well documented, as is the urgency for addressing them. In addition, associations between quality of life, depression, self-esteem, self-criticism, and obesity are now established indicating a need for a better understanding of the links between self-evaluation, affect-regulation and eating behaviours. Methods Compassion has now been identified as a major source of resilience, helpful self-relating and affect regulation. Thus this study used semi-structured interviews to explore the understanding and experiences of compassion in 2 overweight men and 10 women seeking help for weight problems. The interviews examined people's understandings of compassion, their recall of experiences of compassion in childhood, their current experiences of receiving compassion from others, being compassionate to others, being self-compassionate, and whether they would be compassionate or self-critical for relapses in overeating. Interviews were transcribed and analysed using thematic analysis (Qual Res Psychol, 3: 77-101, 2006). Results Participants saw compassion as related to ‘caring’ and being ‘listened to’. However, their recall of earlier experiences of compassion was of primarily practical help rather than emotional engagement. Typically their response to their own relapse and setbacks were self-criticism, self-disgust and even self-hatred rather than self-caring or understanding. Self-critical/hating responses tend to be associated with poor weight regulation. Conclusions When people with weight problems relapse, or struggle to control their eating, they can become quite self-critical, even self-hating, which may increase difficulties with emotionally coping and maintaining healthy lifestyles and eating habits. Although turning to others for support and compassion, and becoming self-compassionate are antidotes to self-criticism, and are associated with better coping and mental health, many participants did not utilise compassionate strategies – often the opposite. It is possible that interventions that include mindfulness and compassion training could be helpful for these difficulties.