• Adipocyte NR1D1 dictates adipose tissue expansion during obesity

      editor: Tontonoz, Peter; senior_editor: James, David E; Hunter, Ann Louise; orcid: 0000-0002-3874-4852; Pelekanou, Charlotte E; Barron, Nichola J; Northeast, Rebecca C; orcid: 0000-0002-3121-2802; Grudzien, Magdalena; Adamson, Antony D; Downton, Polly; orcid: 0000-0002-1617-6153; Cornfield, Thomas; et al. (eLife Sciences Publications, Ltd, 2021-08-05)
      The circadian clock component NR1D1 (REVERBα) is considered a dominant regulator of lipid metabolism, with global Nr1d1 deletion driving dysregulation of white adipose tissue (WAT) lipogenesis and obesity. However, a similar phenotype is not observed under adipocyte-selective deletion (Nr1d1Flox2-6:AdipoqCre), and transcriptional profiling demonstrates that, under basal conditions, direct targets of NR1D1 regulation are limited, and include the circadian clock and collagen dynamics. Under high-fat diet (HFD) feeding, Nr1d1Flox2-6:AdipoqCre mice do manifest profound obesity, yet without the accompanying WAT inflammation and fibrosis exhibited by controls. Integration of the WAT NR1D1 cistrome with differential gene expression reveals broad control of metabolic processes by NR1D1 which is unmasked in the obese state. Adipocyte NR1D1 does not drive an anticipatory daily rhythm in WAT lipogenesis, but rather modulates WAT activity in response to alterations in metabolic state. Importantly, NR1D1 action in adipocytes is critical to the development of obesity-related WAT pathology and insulin resistance.
    • Effect of breakfast cereal type on portion size and nutritional implications.

      Lewis, Isabelle M; Boote, Lucy; Butler, Tom; orcid: 0000-0003-0818-1566 (2021-02-17)
      The present study aimed to assess the effect of different types of breakfast cereal on portion size and the nutritional implications of potential under or overserving. A cross-sectional analysis was performed using one BC from the 7 established BC manufacturing methods (flaking [F], gun puffed [GP], oven puffed [OP], extruded gun puffed [EGP], shredded wholegrain [SW], biscuit formed [BF], and granola). Participants were asked to pour cereal as if they were serving themselves (freepour). Difference between the freepour and recommended serving size (RSS) were calculated (DFR). The Friedman test followed by Dunn's multiple comparison test was used to test for a significant differences between cereal categories. City of Chester, North West of the UK. Adults (n=169; n=110 female, 32±18 years). Freepour values were greater than RSS for all categories of BC. Median values for denser cereals such as SW, granola and oats were significantly (P<0.001) greater than all other categories with granola having the highest median freepour value of 95 g. Median (and range of) DFR weight values for granola were significantly higher than other BCs (50.0 g [-24.0-267.0g], P<0.001). BCs with the lowest median DFRs were F1 (7.0 g [-20-63.0g]), GP (6.0 g [-26.0-69.0g]), EGP (6.0 g [-26.0-56.0g]), OP (5.0 g [-27.0-53.0g]), and BF (0.0 g [-28.2-56.4g]). The degree of overserving may be related to the type of BC with denser cereals more readily overserved. Encouraging manufacturers to reformulate cereals and improving their nutritional properties may have benefit in reducing excess energy intake.
    • eNAMPT Is Localised to Areas of Cartilage Damage in Patients with Hip Osteoarthritis and Promotes Cartilage Catabolism and Inflammation

      Philp, Ashleigh M.; email: as.philp@garvan.org.au; Butterworth, Sam; email: sam.butterworth@manchester.ac.uk; Davis, Edward T.; email: Edward.davis@nhs.net; Jones, Simon W.; email: s.w.jones@bham.ac.uk (MDPI, 2021-06-23)
      Obesity increases the risk of hip osteoarthritis (OA). Recent studies have shown that adipokine extracellular nicotinamide phosphoribosyltransferase (eNAMPT or visfatin) induces the production of IL-6 and matrix metalloproteases (MMPs) in chondrocytes, suggesting it may promote articular cartilage degradation. However, neither the functional effects of extracellular visfatin on human articular cartilage tissue, nor its expression in the joint of hip OA patients of varying BMI, have been reported. Hip OA joint tissues were collected from patients undergoing joint replacement surgery. Cartilage explants were stimulated with recombinant human visfatin. Pro-inflammatory cytokines and MMPs were measured by ELISA and Luminex. Localisation of visfatin expression in cartilage tissue was determined by immunohistochemistry. Cartilage matrix degradation was determined by quantifying proteoglycan release. Expression of visfatin was elevated in the synovial tissue of hip OA patients who were obese, and was co-localised with MMP-13 in areas of cartilage damage. Visfatin promoted the degradation of hip OA cartilage proteoglycan and induced the production of pro-inflammatory cytokines (IL-6, MCP-1, CCL20, and CCL4) and MMPs. The elevated expression of visfatin in the obese hip OA joint, and its functional effects on hip cartilage tissue, suggests it plays a central role in the loss of cartilage integrity in obese patients with hip OA.
    • Enhancing community weight loss groups in a low socioeconomic status area: Application of the COM‐B model and Behaviour Change Wheel

      Coupe, Nia; orcid: 0000-0003-4974-5794; email: n.coupe@chester.ac.uk; email: n.coupe@lancaster.ac.uk; Cotterill, Sarah; orcid: 0000-0001-5136-390X; Peters, Sarah; orcid: 0000-0003-1949-3995 (2021-08-04)
      Abstract: Background: Obesity rates are higher among people of lower socioeconomic status. While numerous health behaviour interventions targeting obesity exist, they are more successful at engaging higher socioeconomic status populations, leaving those in less affluent circumstances with poorer outcomes. This highlights a need for more tailored interventions. The aim of this study was to enhance an existing weight loss course for adults living in low socioeconomic communities. Methods: The Behaviour Change Wheel approach was followed to design an add‐on intervention to an existing local authority‐run weight loss group, informed by mixed‐methods research and stakeholder engagement. Results: The COM‐B analysis of qualitative data revealed that changes were required to psychological capability, physical and social opportunity and reflective motivation to enable dietary goal‐setting behaviours. The resulting SMART‐C booklet included 6 weeks of dietary goal setting, with weekly behavioural contract and review. Conclusion: This paper details the development of the theory‐ and evidence‐informed SMART‐C intervention. This is the first report of the Behaviour Change Wheel being used to design an add‐on tool to enhance existing weight loss services. The process benefitted from a further checking stage with stakeholders.
    • Metabolomics: A Scoping Review of Its Role as a Tool for Disease Biomarker Discovery in Selected Non-Communicable Diseases

      Aderemi, Adewale Victor; email: adewale.aderemi@postgrad.manchester.ac.uk; Ayeleso, Ademola Olabode; email: ademola.ayeleso@adelekeuniversity.edu.ng; Oyedapo, Oluboade Oluokun; email: ooyedapo@yahoo.co.uk; Mukwevho, Emmanuel; orcid: 0000-0001-8800-955X; email: emmanuel.mukwevho@nwu.ac.za (MDPI, 2021-06-25)
      Metabolomics is a branch of ‘omics’ sciences that utilises a couple of analytical tools for the identification of small molecules (metabolites) in a given sample. The overarching goal of metabolomics is to assess these metabolites quantitatively and qualitatively for their diagnostic, therapeutic, and prognostic potentials. Its use in various aspects of life has been documented. We have also published, howbeit in animal models, a few papers where metabolomic approaches were used in the study of metabolic disorders, such as metabolic syndrome, diabetes, and obesity. As the goal of every research is to benefit humankind, the purpose of this review is to provide insights into the applicability of metabolomics in medicine vis-à-vis its role in biomarker discovery for disease diagnosis and management. Here, important biomarkers with proven diagnostic and therapeutic relevance in the management of disease conditions, such as Alzheimer’s disease, dementia, Parkinson’s disease, inborn errors of metabolism (IEM), diabetic retinopathy, and cardiovascular disease, are noted. The paper also discusses a few reasons why most metabolomics-based laboratory discoveries are not readily translated to the clinic and how these could be addressed going forward.
    • Non-Alcoholic Fatty Liver Disease (NAFLD) and Potential Links to Depression, Anxiety, and Chronic Stress

      Shea, Sue; email: sue.shea@warwick.ac.uk; Lionis, Christos; orcid: 0000-0002-9324-2839; email: lionis@galinos.med.uoc.gr; Kite, Chris; orcid: 0000-0003-1342-274X; email: c.kite@chester.ac.uk; Atkinson, Lou; orcid: 0000-0003-1613-3791; email: l.atkinson1@aston.ac.uk; Chaggar, Surinderjeet S.; email: surinder.chaggar@nhs.net; Randeva, Harpal S.; email: harpal.randeva@uhcw.nhs.uk; Kyrou, Ioannis; email: ad6702@coventry.ac.uk (MDPI, 2021-11-16)
      Non-alcoholic fatty liver disease (NAFLD) constitutes the most common liver disease worldwide, and is frequently linked to the metabolic syndrome. The latter represents a clustering of related cardio-metabolic components, which are often observed in patients with NAFLD and increase the risk of cardiovascular disease. Furthermore, growing evidence suggests a positive association between metabolic syndrome and certain mental health problems (e.g., depression, anxiety, and chronic stress). Given the strong overlap between metabolic syndrome and NAFLD, and the common underlying mechanisms that link the two conditions, it is probable that potentially bidirectional associations are also present between NAFLD and mental health comorbidity. The identification of such links is worthy of further investigation, as this can inform more targeted interventions for patients with NAFLD. Therefore, the present review discusses published evidence in relation to associations of depression, anxiety, stress, and impaired health-related quality of life with NAFLD and metabolic syndrome. Attention is also drawn to the complex nature of affective disorders and potential overlapping symptoms between such conditions and NAFLD, while a focus is also placed on the postulated mechanisms mediating associations between mental health and both NAFLD and metabolic syndrome. Relevant gaps/weaknesses of the available literature are also highlighted, together with future research directions that need to be further explored.