Lipase Inhibitors for Obesity: A Review Liu, Tian-Tian; Liu, Xiao-Tian; Chen, Qing-Xi ...
Biomedicine & pharmacotherapy,
August 2020, 2020-Aug, 2020-08-00, 2020-08-01, Letnik:
128
Journal Article
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Odprti dostop
•The role of pancreatic lipase inhibitor in lipid metabolism is elaborated.•The existing microbial sources of high activity and high yield lipase was summarized, to provide reference for ...researchers.•Lipase inhibitors from natural products was summarize for readers’ reference.•The manuscript has summarized the research status of pancreatic lipase inhibitor on anti-obesity and provided new ideas to solve the bottleneck problem.
With the rapid increase in the population of obese individuals, obesity has become a global problem. Many kinds of chronic metabolic diseases easily caused by obesity have received increasing attention from researchers. People are also striving to find various safe and effective treatment methods as well as anti-obesity medicines. Pancreatic lipase (PL) inhibitors have received substantial attention from researchers in recent years, and PL inhibitors from natural products have attracted much attention due to their structural diversity, low toxicity and wide range of sources. They have been used in the intestinal tract, blood, and the central nervous system with no side effects, and these advantages could lead to a new generation of diet pills or health care products with great development potential. This article is mainly aimed at discussing the research of obesity drug treatment with PL inhibitors and offers a brief review of related properties and the use of PL inhibitors in the field of weight loss.
The dramatic increase in obesity is putting people under increasing pressure. Lipase inhibitors, as a kind of effective anti-obesity drug, have attracted more and more researchers' attention in ...recent years because of their advantages of acting on the intestinal tract and having no side effects on the central nervous system. In this study, lipase inhibitor Fu Brick Theophylline (FBT) was screened based on enzyme molecular dynamics, and the inhibition mechanism of lipase inhibitors on obesity was analyzed and discussed at the cellular level and animal model level. We found that FBT had high inhibition effects of lipase with an
of 1.02~0.03 μg/mL. Firstly, the laboratory used 3T3-L1 proadipocytes as models, flow cytometry was used to detect the effects of FBT on the cycle, apoptosis and intracellular ROS activity of proadipocytes. To study the contents of triglyceride, total cholesterol, related metabolites and related gene and protein expression in adipocytes. The results showed that FBT could reduce ROS production and inflammatory factor mRNA expression during cell differentiation. Secondly, by establishing the animal model of high-fat feed ob nutritional obese mice, the morphological observation and gene expression analysis of body weight, fat rate, adipocyte and hepatocyte metabolism of FBT obese mice were further discussed. It was proven that FBT can effectively reduce the degree of fatty liver, prevent liver fibrosis and fat accumulation, and improve the damage of mitochondrial membrane structure. This study provides a theoretical basis for the screening and clinical treatment of lipase inhibitors.
Induction of the transcription factor Irf8 in the common dendritic cell progenitor (CDP) is required for classical type 1 dendritic cell (cDC1) fate specification, but the mechanisms controlling this ...induction are unclear. In the present study Irf8 enhancers were identified via chromatin profiling of dendritic cells and CRISPR/Cas9 genome editing was used to assess their roles in Irf8 regulation. An enhancer 32 kilobases (kb) downstream of the Irf8 transcriptional start site (+32-kb Irf8) that was active in mature cDC1s was required for the development of this lineage, but not for its specification. Instead, a +41-kb Irf8 enhancer, previously thought to be active only in plasmacytoid dendritic cells, was found to also be transiently accessible in cDC1 progenitors, and deleting this enhancer prevented the induction of Irf8 in CDPs and abolished cDC1 specification. Thus, cryptic activation of the +41-kb Irf8 enhancer in dendritic cell progenitors is responsible for cDC1 fate specification.
Classical type 1 dendritic cells (cDC1s) are required for antiviral and antitumor immunity, which necessitates an understanding of their development. Development of the cDC1 progenitor requires an ...E-protein-dependent enhancer located 41 kilobases downstream of the transcription start site of the transcription factor Irf8 (+41-kb Irf8 enhancer), but its maturation instead requires the Batf3-dependent +32-kb Irf8 enhancer. To understand this switch, we performed single-cell RNA sequencing of the common dendritic cell progenitor (CDP) and identified a cluster of cells that expressed transcription factors that influence cDC1 development, such as Nfil3, Id2 and Zeb2. Genetic epistasis among these factors revealed that Nfil3 expression is required for the transition from Zeb2
and Id2
CDPs to Zeb2
and Id2
CDPs, which represent the earliest committed cDC1 progenitors. This genetic circuit blocks E-protein activity to exclude plasmacytoid dendritic cell potential and explains the switch in Irf8 enhancer usage during cDC1 development.
Development and function of conventional dendritic cell (cDC) subsets, cDC1 and cDC2, depend on transcription factors (TFs) IRF8 and IRF4, respectively. Since IRF8 and IRF4 can each interact with TF ...BATF3 at AP1-IRF composite elements (AICEs) and with TF PU.1 at Ets-IRF composite elements (EICEs), it is unclear how these factors exert divergent actions. Here, we determined the basis for distinct effects of IRF8 and IRF4 in cDC development. Genes expressed commonly by cDC1 and cDC2 used EICE-dependent enhancers that were redundantly activated by low amounts of either IRF4 or IRF8. By contrast, cDC1-specific genes relied on AICE-dependent enhancers, which required high IRF concentrations, but were activated by either IRF4 or IRF8. IRF8 was specifically required only by a minority of cDC1-specific genes, such as Xcr1, which could distinguish between IRF8 and IRF4 DNA-binding domains. Thus, these results explain how BATF3-dependent Irf8 autoactivation underlies emergence of the cDC1-specific transcriptional program.
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•cDC identity relies on cis-regulatory elements redundantly controlled by IRF4 and IRF8•cDC1 is distinguished from cDC2 by the use of an AICE-dependent gene program•An AICE-dependent gene program requires high levels of either IRF4 or IRF8•Specific cis-regulatory elements distinguish between IRF4 and IRF8 DNA-binding domains
Development and function of conventional dendritic cell (cDC) subsets, cDC1 and cDC2, depend on IRF8 and IRF4. Kim et al. demonstrate that the basis for their distinct effects results from the higher level of IRF expressed in cDC1, which is required to selectively engage AICEs that determine cDC1 identity.
China is one of the countries with the highest incidence of gastric cancer. There are differences in epidemiological characteristics, clinicopathological features, tumor biological characteristics, ...treatment patterns, and drug selection between gastric cancer patients from the Eastern and Western countries. Non‐Chinese guidelines cannot specifically reflect the diagnosis and treatment characteristics for the Chinese gastric cancer patients. The Chinese Society of Clinical Oncology (CSCO) arranged for a panel of senior experts specializing in all sub‐specialties of gastric cancer to compile, discuss, and revise the guidelines on the diagnosis and treatment of gastric cancer based on the findings of evidence‐based medicine in China and abroad. By referring to the opinions of industry experts, taking into account of regional differences, giving full consideration to the accessibility of diagnosis and treatment resources, these experts have conducted experts’ consensus judgement on relevant evidence and made various grades of recommendations for the clinical diagnosis and treatment of gastric cancer to reflect the value of cancer treatment and meeting health economic indexes. This guideline uses tables and is complemented by explanatory and descriptive notes covering the diagnosis, comprehensive treatment, and follow‐up visits for gastric cancer.
Hydrogen‐bonded organic frameworks (HOFs) possess various merits, such as high porosity, tunable structure, facile modification, and ready regeneration. These properties have yet to be explored in ...the context of new functional HOF materials. The facile and inexpensive electrophoretic deposition (EPD) method applied in this study generated a transparent HOF film at room temperature in just 2 min and is applicable to other HOFs. The resulting film exhibited reversible electrochromism with the advantage of long cycle life (>500 cycles). More strikingly, this all‐organic film could be readily regenerated (through rinsing with DMF and redeposition) and showed tunable electrochromic behavior (through low‐cost postsynthetic modification) with the ability to undergo successive color changes, which is difficult to achieve with conventional electrochromic materials. An electrochromic device was manufactured to further demonstrate the application potential of the film.
Facile and efficient electrophoretic deposition was used to prepare an electrochromic hydrogen‐bonded organic framework film (see picture), which exhibited reversible electrochromism with the advantages of long cycle life, ready regeneration, and tunable electrochromic behavior. An electrochromic device was manufactured with the film to further demonstrate its application potential.
During viral infection, sensing of cytosolic DNA by the cyclic GMP-AMP synthase (cGAS) activates the adaptor protein STING and triggers an antiviral response. Little is known about the mechanisms ...that determine the kinetics of activation and deactivation of the cGAS-STING pathway, ensuring effective but controlled innate antiviral responses. Here we found that the ubiquitin ligase Trim38 targets cGas for sumoylation in uninfected cells and during the early phase of viral infection. Sumoylation of cGas prevented its polyubiquitination and degradation. Trim38 also sumoylated Sting during the early phase of viral infection, promoting both Sting activation and protein stability. In the late phase of infection, cGas and Sting were desumoylated by Senp2 and subsequently degraded via proteasomal and chaperone-mediated autophagy pathways, respectively. Our findings reveal an essential role for Trim38 in the innate immune response to DNA virus and provide insight into the mechanisms that ensure optimal activation and deactivation of the cGAS-STING pathway.
•Trim38 deficiency enhances susceptibility to DNA virus infection•Sumoylation of cGas and Sting promotes their stability during early infection•In the late phase of infection, cGas and Sting are desumoylated by Senp2•Desumoylation of cGas and Sting leads to their degradation by different mechanisms
Hu et al. show that sumoylation of the DNA sensor cGas and the adaptor Sting by Trim38 and their subsequent desumoylation by Senp2 ensure an efficient triggering of the cGAS-STING pathway in the early phase of DNA virus infection, as well as its timely termination upon resolution of infection.
With a dinuclear zinc-ProPhenol complex as a catalyst, an efficient and novel 3 + 3 annulation of indoline-2-thiones and isatylidene malononitriles has been successfully developed via the Brønsted ...base and Lewis acid cooperative activation model. This practical methodology gives access to a broad range of chiral spiroindoline-3,4'-thiopyrano2,3-
indole derivatives in good yields with excellent levels of enantioselectivities (up to 88% yield and 99% ee).
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