• 2018-07
  • 2018-10
  • 2018-11
  • 2019-04
  • 2019-05
  • 2019-06
  • 2019-07
  • To the best of our knowledge


    To the best of our knowledge, this study was the first to demonstrate in vitro and in vivo that the lipolytic effect of kinsenoside results from coordination between PKA and AMPK pathways. We validated the lipolytic effect of kinsenoside in vivo and the effect of PKA activation on the modulating AMPK function for FA hydrolysis through HSL and perilipin activation.
    Conclusion This study indicated that in addition to activating AMPK, kinsenoside activated HSL and perilipin through a PKA-dependent mechanism to facilitate lipolysis and to reduce fat accumulation both in vitro and in vivo. Thus, kinsenoside could be a promising adjuvant for the prophylaxis of obesity-associated complications.
    Introduction Throughout evolution, animals have developed such that excess fats ML 154 and sugars not immediately required for energy are stored. This biological function, invaluable for survival during times of scarce food and famine, has become less practical in the developed world, where sustenance abounds. The excess triglyceride storage resulting from the modern influx of nutrient-rich foods has become the foundation for metabolic diseases such as obesity. A better understanding of the mechanisms by which fat storage is regulated may prove to be medically indispensable for such diseases. In mammals, triglycerides are stored within structures known as lipid droplets [1]; however, much is still unknown about how lipid droplet formation and morphology is regulated. In an attempt to identify genes involved in this process, genome-wide RNAi screens have been performed in Drosophila cell culture since lipid droplet structure is well conserved from flies to humans [2], [3]. These screens identified several ML 154 of genes that when knocked down generated visible and quantifiable lipid droplet morphology phenotypes. One subset of these genes included various components of the spliceosome. Alternative splicing is a critical part of regulating gene expression; over 90% of the human transcriptome is alternatively spliced [4]. Identifying the role of alternative splicing in the function of multiple biological and disease processes has driven many research initiatives in recent years [5]. Specifically, links have been made between mRNA processing and the control of carbohydrate and lipid metabolism. For example, alternative splicing of glucose 6-phosphate dehydrogenase, the rate-limiting enzyme of the pentose phosphate pathway, is regulated in response to altered dietary input [6]. Additionally, down-regulation of the splicing factor SFRS10 in humans has been linked to enhanced lipogenesis and lipid accumulation in obese patients [7]. However, the mechanisms whereby the splicing machinery controls triglyceride storage and lipid droplet morphology are not fully understood. In Drosophila, around 61% of multi-exon genes are alternatively spliced [8]. The regulation of nutrient storage and metabolism is also highly conserved in Drosophila[9], [10]. Therefore, the fly can serve as an excellent system for understanding the role of the splicing machinery in the control of lipid metabolism. In this study, we used the Drosophila fat body (the mammalian liver and adipose equivalent) to assess the role of the proteins involved in the earliest stages of the splicing reaction (including parts of the U1 snRNP, U2AF, and SR proteins) in the regulation of lipid storage. The expression of these representative splicing factors involved in the splicing commitment complex were decreased using RNAi in larval and adult fat bodies and assayed for total triglyceride content. Not surprisingly, we found that decreasing the expression of a number of general splicing factors produced animals with decreased triglyceride levels. Interestingly, knockdown of the SR protein 9G8 results in distinctive triglyceride storage defects, depending on the stage of development. These changes in triglyceride levels were not, however, accompanied by a similar change in glycogen storage, suggesting that triglyceride metabolism is being specifically affected by 9G8-induced splicing of target genes. Decreasing 9G8 also affects the splicing of the β-oxidation enzyme CPT1, potentially contributing to the observed lipid storage phenotype. This study provides in vivo evidence for a complex connection between mRNA splicing and fat metabolism.