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Non-alcoholic steatosis (NAFLD) and steatohepatitis (NASH) are two highly prevalent human disorders for which therapy remains suboptimal. Bile acids are signaling molecules acting on two main receptors the Farnesoid-x-receptor (FXR) and G protein coupled receptor GPB AR1. Clinical trials have shown that FXR agonism might result in side effects along with lack of efficacy in restoring liver histopathology. For these reasons a multi-targets therapy combined FXR agonists with agent targeting additional molecular mechanisms might have improved efficacy over selective FXR agonists. In the present study we have compared the effects of BAR502, a dual FXR/GPBAR1 ligand) alone or in combination with ursodeoxycholic acid (UDCA) in a model of NAFLD/NASH induced by feeding mice with a Western diet for 10 weeks. The results demonstrated that while BAR502 and UDCA partially protected against liver damage caused by Western diet, the combination of the two, reversed the pro-atherogenic lipid profile and completely reversed the histopathology damage, attenuating liver steatosis, ballooning, inflammation and fibrosis. Additionally, while both agents increased insulin sensitivity and bile acid signaling, the combination of the two, modulated up top 85 genes in comparison of mice feed a Western diet, strongly reducing expression of inflammatory markers such as chemokines and cytokines. Additionally, the combination of the two agents redirected the bile acid metabolism toward bile acid species that are GPBAR1 agonist while reduced liver bile acid content and increased fecal excretion. Together, these data, highlight the potential role for a combinatorial therapy based on BAR502 and UDCA in treating of NAFLD.

This paper presents a format from the creative arts, refocused for application in management studies, as a method to enhance and support the development of strategic thinking. It involves the application of multi-page paper constructions (zines) within facilitated sessions to enhance imaginative strategic thinking by both management learners and practitioners. It draws on a longitudinal case study of the six-phase evolution of affordances of a zine as a method for reflective, creative and connected thinking. The focus moves from purely personal private reflections to the possibility of deploying zines for collective reflection and action. Specific examples are provided of zine workshops and events. Strategic thinking relates to volatility, uncertainty, complexity and ambiguity (VUCA). The affordances of zines relating to tangibility, efficiency and mental processes appear well-suited to a VUCA context. The paper concludes with reflections on the nature of multi-disciplinary and trans-disciplinary collaborations such as this one.