Novel Anti-Obesity Effects of Beer Hops Compound Xanthohumol: Role of Ampk Signaling Pathway

Obesity, a chronic disease, is a global epidemic that affects millions of lives and increases the risk of several comorbidities such as Type 2 diabetes, musculoskeletal disorders, cardiovascular disease, and cancer. Obesity is the leading cause of death globally, and is associated with an excessive accumulation of white adipose tissue (WAT). Although obesity is a serious condition, safe, long-term drug therapies are limited. A second type of adipose tissue is known as brown adipose tissue (BAT), which functions as an energy dissipater in the form of heat, as opposed to energy storing WAT. Previous research has shown that the mitochondrial uncoupling protein 1 (UCP1), activates the thermogenic properties of BAT [1]. WAT lacks the expression of UCP1 and therefore has no protective mechanisms against obesity and stores energy in the form of triglycerides. Thermogenic BAT has been identified in adult humans [2], as such, this discovery has been an attractive target for anti-obesity therapy. Recently, studies have suggested that WAT can be transdifferentiated into brown-like beige adipose tissue (BeAT). This transdifferentiation process is referred to as “beiging” and is mediated by the activation of the sympathetic nervous system. Activation of BeAT, similar to BAT, generates heat at the expense of ATP. Additionally, immune cells like macrophages play an important role in the induction of thermogenesis in WAT and contribute to the beiging of WAT [3]. Samuels v Current treatments for obesity, as well as “browning” agents, propose their own risks to humans and are not ideal long-term solutions for anti-obesity therapy. Consequently, many phytochemicals have been explored for their safe anti-obesity affects and as browning agents. Recently, xanthohumol (XN), a prenylated flavonoid found in Hops flowers, has been reported to inhibit adipogenesis and stimulate the apoptosis of adipocytes [4]. However, there are no published studies demonstrating the effects of XN on thermogenesis. In this current study, we will explore novel anti-obesity effects of XN to propose a multi-faceted approach for prevention and treatment of obesity. We propose to investigate the direct and indirect effects of XN on the induction of beiging in white adipocytes. Furthermore, we will investigate the role of adenosine monophosphate activated kinase (AMPK) signaling pathway in the induction of beiging. The in vitro cell culture models utilized in this study are murine adipocyte (3T3-L1) and macrophage (RAW264.7) cell lines. Cell viability assay, Western blotting, ELISA, MitoTracker Green™, Oil Red O staining, AdipoRed™ assay, and a Transwell co-culturing system are employed to demonstrate the effects of XN on beiging and the role of AMPK pathway in XN-induced beiging. Our data suggests that XN has the ability to directly induce transdifferentiation of white to beige adipocytes and indirectly induce beiging by activating anti-inflammatory M2 macrophages. Furthermore, data also indicates a role of the AMPK pathway in XN-mediated anti-obesity effects

Issues Related to Text Comprehensibility: The Future of Readability

Cet article situe la lisibilité dans une perspective historique. Il présente un tour d’horizon des différentes mesures de la lisibilité qui existent ainsi que de leur impact, s’intéresse aux différentes composantes qui influencent la construction du sens et présente des préoccupations pédagogiques relatives à l’intelligibilité.This paper places readability in an historical context, reviews the development of present day formulas and their liabilities, explores other factors that influence meaning making, and considers comprehensibility from the point of view of the educator. The authors conclude that determining how easy or how difficult a particular book may be for a particular reader is a complex task. There may be a time when it is possible to develop a formula that includes all elements that impact upon readability, but at present, estimating text comprehensibility requires personal judment

Legal Crib Sheets: Promoting Deep Levels of Processing and Learning

The article demonstrates that legal crib sheets encourage deep levels of information processing, an activity that should enhance students\u27 learning and long-term memory. Levels of processing theory states that memory processes exist on a depth continuum; comprehension and synthesis are examples of deep cognitive processes that enhance memory, whereas simple repetition or examining surface characteristics of words are examples of shallow cognitive processes (Craik & Lockhart, 1972). The use of legal crib sheets allowed students to attain significantly higher overall mean test scores while not affecting their long-term retention of the material. Deeper levels of processing occurred because the students manipulated course infOrmation in preparing legal crib sheets

Evaporation of a packet of quantized vorticity

A recent experiment has confirmed the existence of quantized turbulence in superfluid He3-B and suggested that turbulence is inhomogenous and spreads away from the region around the vibrating wire where it is created. To interpret the experiment we study numerically the diffusion of a packet of quantized vortex lines which is initially confined inside a small region of space. We find that reconnections fragment the packet into a gas of small vortex loops which fly away. We determine the time scale of the process and find that it is in order of magnitude agreement with the experiment.Comment: figure 1a,b,c and d, figure2, figure

Novel Anti-Obesity Effects of Beer Hops Compound Xanthohumol: Role of AMPK Signaling Pathway

Background: Obesity alters adipose tissue metabolic and endocrine functioning, leading to an increased adiposity and release of pro-inflammatory cytokines. Various phytochemicals have been reported to contribute to the beiging of white adipose tissue in order to ameliorate obesity by increasing thermogenesis. Here, we show that the prenylated chalcone, xanthohumol (XN), induces beiging of white adipocytes, stimulates lipolysis, and inhibits adipogenesis of murine 3T3-L1 adipocytes and primary human subcutaneous preadipocytes and these effects are partly mediated by the activation of the AMP-activated protein kinase (AMPK) signaling pathway. Methods: 3T3-L1 adipocytes and primary human subcutaneous preadipocytes were differentiated using a standard protocol and were treated with various concentrations of XN, dorsomorphin, an AMPK inhibitor, or AICAR, an AMPK activator, to investigate the effects on adipogenesis, beiging and lipolysis. Results: XN induced beiging of white adipocytes as witnessed by the increased expression of beige markers CIDE-A and TBX-1. XN increased mitochondrial biogenesis, as evidenced by increased mitochondrial content, enhanced expression of PGC-1α, and the thermogenic protein UCP1. Following 24 h of treatment, XN also increased oxygen consumption rate. XN stimulated lipolysis of mature 3T3-L1 and primary human subcutaneous adipocytes and inhibited adipogenesis of maturing adipocytes. XN activated AMPK and in turn, XN-induced upregulation of UCP1, p-ACC, HSL, and ATGL was downregulated in the presence of dorsomorphin. Likewise, an XN-induced decrease in adipogenesis was reversed in the presence of dorsomorphin. Conclusions: Taken together, XN demonstrates anti-obesity effects by not only inducing beiging but also decreasing adipogenesis and inducing lipolysis. The anti-obesity effects of XN are partly mediated by AMPK signaling pathway suggesting that XN may have potential therapeutic implications for obesity