ObjectiveFibroblast growth factor 21 (FGF21) is an endocrine hormone that regulates metabolic homeostasis. Previous work has suggested that impairment of FGF21 signaling in adipose tissue may occur through downregulation of the obligate FGF21 co-receptor, β-klotho, which leads to “FGF21 resistance” during the onset of diet-induced obesity. Here, we sought to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance and whether other mechanisms also contribute to FGF21 resistance in vivo.MethodsWe generated adipose-specific β-klotho transgenic mice to determine whether maintenance of β-klotho expression in adipose tissue prevents FGF21 resistance in vivo.Resultsβ-klotho protein levels are markedly decreased in white adipose tissue, but not liver or brown adipose tissue, during diet-induced obesity. Maintenance of β-klotho protein expression in adipose tissue does not alleviate impaired FGF21 signaling in white adipose or increase FGF21 sensitivity in vivo.ConclusionsIn white adipose tissue, downregulation of β-klotho expression is not the major mechanism contributing to impaired FGF21 signaling in white adipose tissue.

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Background Growing evidence indicates patients’ survivorship outcomes can be enhanced through active engagement in a  multi-modal cancer prehabilitation programme (MCPP), although this intervention is not uniformly embedded as a standard of care.  MCPP aims to optimise patients physiologically and psychologically for cancer treatments, shorten recovery time, reduce complications, promote healthier lifestyles and improve quality of life.  South Eastern Health and Social Care Trust (SET) developed and evaluated a  system-wide collaborative approach  to MMCP across three tumour groups (colorectal, lung, head and neck cancer).  Addressing the lack of qualitative evaluation of MCPPs, this paper explores mechanisms promoting feasibility and acceptability of MCPP from patients’ and interdisciplinary professionals’ perspectives. Methods Semi-structured virtual one-to-one interviews were conducted with 24 interdisciplinary professionals and nine patients.  Transcripts were recorded, transcribed verbatim and themes developed using Framework Analysis.   Results Analysis of findings identified four themes providing an in-depth understanding of key elements required to develop and deliver a MCPP:   1) Planning: Building the team, 2) Shared vision to develop and tailor the MCPP to meet patient needs, 3) Delivering the MCPP and 4) Moving forward - improving the MCPP. Conclusion The system-wide collaborative approach to developing a MCPP at SET was deemed both feasible and acceptable.  Success was attributed to visionary leadership, alongside a diverse group of interdisciplinary professionals being engaged, motivated and committed to improving patient outcomes.  Iterative, responsive troubleshooting during delivery facilitated successful implementation.  Greater adherence to provision of prescriptive high intensity exercise within the programme may further promote enhanced patient outcomes.