Preadipocytes are capable of differentiating into lipid lade
Preadipocytes are capable of differentiating into lipid-laden mature adipocytes. Lipid droplets are a prominent morphological feature of mature adipocytes, which is accumulated and maintained during adipocytes differentiation . In this study, rHhip treatment increased lipid accumulation, as well as PPARγ mRNA expression, whereas the protein level had no statistical change. As a member of the Nuclear Receptor (NR) superfamily of ligand-activated Transcription Factors (TFs), PPARγ have been shown to participate in the regulation of adipocyte survival and differentiation, insulin sensitivity, and lipogenesis [27,28]. Based on the previous finding, we speculated, with the exception of transcriptional regulation, the mRNA and protein expression of PPARγ were governed by post-transcriptional and post-translational modifications. Post-translational modifications including phosphorylation, ubiquitination, O-GlcNAcylation, and S-nitrosylation could influence the protein stability and transcriptional activity of PPARγ [, , , ]. Thus the differences between PPARγ mRNA and protein level may be due to post-translational modification. Our data revealed Hhip promoted differentiation of adipocytes via inhibiting Hh signaling. Targeting Hh signaling could suppress high-fat-diet-induced obesity and improve glucose tolerance and insulin sensitivity during postnatal life . Activation of Hh signaling pathway by PM resulted in decreased lipid accumulation, but did not alter mature adipocyte number. Whereas, after treatment with specific Hh inhibitor cyclopamine, the level of Gli1 decreased but the lipid accumulation of human multipotent adipose-derived stem (hMADS) Cyclic di-GMP mg were not changed . Up to now, most studies on Hh pathway inhibitors have been focused on Smo and its downstream, cyclopamine, jervine, GDC-0449, LDE-225, IPI-926 and CUR61414 are widely reported SMO agonist. GANTs and Arsenic Trioxide are known inhibitor of Gli transcription factors , however, the only inhibitor that have been reported to target the upstream of Hh is Robotnikinin, Robotnikinin inhibits the Shh pathway by directly targeting Shh . The regulation of Hhip on adipocyte adipogenesis can provide further insights into the function of the signaling pathway.
Conflicts of interest
Acknowledgments This work was supported by grants from the National Natural Science Foundation of China [Grant no. 31802047] and the National Science and Technology Major Project of China [2016ZX08006003].
Introduction It has been widely recognised that forensic reconstruction is complex. The interaction between many disciplines, institutions, corporate and individual actors, have produced a matrix that spans science and the law, encompassing policing, justice, research and policy. There can be a danger in oversimplifying when seeking to classify, but it is helpful to consider the observation that individuals can have different approaches when it comes to addressing and understanding complex systems. Berlin  outlined the contrast between the approaches of the ‘hedgehog’ (that knows one big thing) and the ‘fox’ (that knows many things) first articulated by the Greek poet Archilochus. The strength of ‘hedgehogs’ has been characterised as the ability to have a clear focus and a single unified view of the world that provides clarity and confidence in understanding the interacting factors at play. The ‘fox’ in contrast is characterised by seeing complexity and nuance and having a more broad, less defined view of the world that is flexible to change in the light of new information and experience. Considering this contrast between the ways of thinking and producing knowledge of multiple actors within a complex system such as forensic science, with its ultimate aim of forensic reconstruction, offers helpful insights. In the last 10 years forensic science has faced significant challenges to its validity , ,  and the concomitant calls for a scientific evidence base to underpin the discipline , , , , . The calls for these challenges to be addressed range from addressing specific issues such as developing empirical evidence bases to understand the dynamics of trace evidence (such as Morgan et al. , Meakin et al. ) and developing the best approaches to convey weight and significance within forensic interpretations (such as Cook et al. ), through to the call for a unified approach that addresses root causes of the issues that have been exposed within forensic science (such as Margot , Roux et al. , Morgan ). In addressing these challenges there have been broadly two genres of approach taken. One approach has been to identify clearly defined solutions to address specific challenges that have been identified (such as ensuring quality standards of a particular process or form of analysis). In contrast there have also been more broad, often more conceptual articulations of the complex system of forensic science and calls to address the challenges in a way that takes into account the different actors (individuals and institutions), different infrastructures within which knowledge is being created, different drivers of the multiple actors, and critically, the interconnections and feedbacks within that system. To address the challenges facing forensic science it is important to consider the strengths of each approach and resist the tendency to create a dichotomy between the perceived chasm that exists between the ‘hedgehog’ approach (that tends towards finding a single organising principle to explain complexity and offer a solution to a challenge), and the ‘fox’ approach (that holds a range of different views that at times can appear contradictory but seeks to identify the diverse factors that contribute to that complexity).