更新于：2024-05-01

LIPE

激素敏感性脂肪酶

更新于：2024-05-01

基本信息

别名

Hormone-sensitive lipase、HSL、lipase E, hormone sensitive type

+ [5]

简介

Lipase with broad substrate specificity, catalyzing the hydrolysis of triacylglycerols (TAGs), diacylglycerols (DAGs), monoacylglycerols (MAGs), cholesteryl esters and retinyl esters (PubMed:8812477, PubMed:15955102, PubMed:15716583, PubMed:19800417). Shows a preferential hydrolysis of DAGs over TAGs and MAGs and preferentially hydrolyzes the fatty acid (FA) esters at the sn-3 position of the glycerol backbone in DAGs (PubMed:19800417). Preferentially hydrolyzes FA esters at the sn-1 and sn-2 positions of the glycerol backbone in TAGs (By similarity). Catalyzes the hydrolysis of 2-arachidonoylglycerol, an endocannabinoid and of 2-acetyl monoalkylglycerol ether, the penultimate precursor of the pathway for de novo synthesis of platelet-activating factor (By similarity). In adipose tissue and heart, it primarily hydrolyzes stored triglycerides to free fatty acids, while in steroidogenic tissues, it principally converts cholesteryl esters to free cholesterol for steroid hormone production (By similarity).

关联

项与 LIPE 相关的药物

Crocin

藏红花素

靶点

LIPE

作用机制

激素敏感性脂肪酶抑制剂 [+1]

在研机构-

原研机构

Kyushu University

在研适应症-

非在研适应症

脂质代谢紊乱 [+3]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

B-105

靶点

LIPE

作用机制

激素敏感性脂肪酶抑制剂

在研机构-

原研机构

BalOnco GmbH

在研适应症-

非在研适应症

代谢性疾病 [+1]

最高研发阶段无进展

首次获批国家/地区-

首次获批日期1800-01-20

项与 LIPE 相关的临床试验

IRCT20221109056447N1 / Recruiting临床2期IIT

Investigating the effect of crocin on quality life, anxiety and depression in patients with multiple sclerosis in a placebo-controlled randomized double blind clinical trial

开始日期2023-11-22

申办/合作机构-

NCT06187818 / Active, not recruitingN/AIIT

Study of Crocin on Cardiac Function Protection in Patients With Breast Cancer Undergoing Neoadjuvant Chemotherapy Based on Color Doppler Ultrasound Combined With Myocardial Zymogram

Foreign data show that: 1807 tumor patients were followed up for 7 years, 33% of them died of heart disease and 51% of them died of the tumor itself. In China, the number of cancer patients undergoing chemotherapy is increasing rapidly every year. How to protect the heart of chemotherapy patients from the damage of chemotherapy drugs (especially anthracyclines) is a problem that clinicians must face.In order to further confirm the clinical efficacy and value of saffron total glycosides tablets in the protection of central function of breast cancer neoadjuvant patients with anthracycline based chemotherapy scheme, the project plans to follow up and observe the research of saffron total glycosides on the protection of cardiac function of breast cancer neoadjuvant patients with chemotherapy based on cardiac color ultrasound combined with myocardial zymography, and randomly group to confirm the effectiveness of saffron total glycosides tablets on cardiac protection, Based on the clinical observation and research on the effect of traditional Chinese medicine on the cardiotoxicity of anthracycline drugs, confirm its efficacy, explore the mechanism of cardiac protection, and explore the drug use method of synergism and toxicity reduction of anthracycline drugs in combination with this active ingredient.

开始日期2023-09-01

申办/合作机构

山东省千佛山医院

ChiCTR2400082396 / Completed早期临床1期IIT

Effectiveness and safety of Crocin tablets in the treatment of cardiac manifestions (syndrome of blood stasis) in patients with post-coronavirus disease 2019 condition: a randomized, double-blind, placebo-controlled clinical tria

开始日期2023-02-23

申办/合作机构-

100 项与 LIPE 相关的临床结果

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100 项与 LIPE 相关的转化医学

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0 项与 LIPE 相关的专利（医药）

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2,953

项与 LIPE 相关的文献（医药）

2024-07-01·Biochemistry and biophysics reports

Effects of swimming in cold water on lipolysis indicators via fibroblast growth factor-21 in male Wistar rats.

Article

作者: Sara Shams ; Mostafa Tavasolian ; Sadegh Amani-Shalamzari ; Pezhman Motamedi ; Hamid Rajabi ; Katja Weiss ; Beat Knechtle

This study aimed to investigate the effects of swimming in cold water on the release of FGF21 from various tissues and its impact on fat metabolism. Twenty Wistar rats were randomly divided into three groups: untrained (C), trained in thermo-neutral water (TN, 30 °C) and trained in cold water (TC, 15 °C). The training groups swam intervals (2-3 min) until exhaustion, 1 min rest, three days a week for six weeks, with 3-6% bodyweight load. The mRNA expression of variables was determined in white fat tissue (WAT), and FGF21 protein was also measured in the liver, brown fat tissue (BAT), serum, and muscle. The experimental protocols resulted in lower body weight gain, associated with reduced WAT volume; the most remarkable improvement was observed in the TC group. Swimming significantly increased FGF21 protein levels in WAT, BAT, and muscle tissues compared to the C group; substantial increases were in the TC group. Changes in FGF21 were highly correlated with the activation of genes involved in fat metabolisms, such as CPT1, CD36, and HSL, and with glycerol in WAT. The findings indicate a positive correlation between swimming in cold water and the activation of genes involved in fat metabolism, possibly through FGF21 production, which was highly correlated with fat-burning genes.

2024-03-01·Animal nutrition (Zhongguo xu mu shou yi xue hui)

The role of vitamin E in polyunsaturated fatty acid synthesis and alleviating endoplasmic reticulum stress in sub-adult grass carp (Ctenopharyngodon idella)

Article

作者: Yao, Ke ; Feng, Lin ; Jiang, Wei-Dan ; Liu, Yang ; Zhang, Lu ; Mi, Hai-Feng ; Zhou, Xiao-Qiu ; Wu, Pei

Vitamin E (VE) is an essential lipid-soluble vitamin that improves the fish flesh quality. However, the underlying molecular mechanisms remain unclear. This study aimed to investigate the effects of VE on growth performance and flesh quality in sub-adult grass carp (Ctenopharyngodon idella). A total of 450 fish (713.53 ± 1.50 g) were randomly divided into six treatment groups (three replicates per treatment) and fed for nine weeks with different experimental diets (dietary lipid 47.8 g/kg) that contained different levels of VE (5.44, 52.07, 96.85, 141.71, 185.66, and 230.12 mg/kg diet, supplemented as dl-α-tocopherol acetate). Notably, the treatment groups that were fed with dietary VE ranging from 52.07 to 230.12 mg/kg diet showed improvement in the percent weight gain, special growth rate, and feed efficiency of grass carp. Moreover, the treatment groups supplemented with dietary VE level of 141.71, 185.66, and 230.12 mg/kg diet showed enhancement in crude protein, lipid, and α-tocopherol contents in the muscle, and the dietary levels of VE ranging from 52.07 to 141.71 mg/kg diet improved muscle pH_24h and shear force but reduced muscle cooking loss in grass carp. Furthermore, appropriate levels of VE (52.07 to 96.85 mg/kg diet) increased the muscle polyunsaturated fatty acid content in grass carp. Dietary VE also increased the mRNA levels of fatty acid synthesis-related genes, including fas, scd-1, fad, elovl, srebp1, pparγ, and lxrα, and up-regulated the expression of SREBP-1 protein. However, dietary VE decreased the expression of fatty acid decomposition-related genes, including hsl, cpt1, acox1, and pparα, and endoplasmic reticulum stress-related genes, including perk, ire1, atf6, eif2α, atf4, xbp1, chop, and grp78, and down-regulated the expression of p-PERK, p-IRE1, ATF6, and GRP78 proteins. In conclusion, dietary VE increased muscle fatty acid synthesis, which may be partly associated with the alleviation of endoplasmic reticulum stress, and ultimately improves fish flesh quality. Moreover, the VE requirements for sub-adult grass carp (713.53 to 1590.40 g) were estimated to be 124.9 and 122.73 mg/kg diet based on percentage weight gain and muscle shear force, respectively.

2024-02-21·Journal of dairy science

Role of diacylglycerol O-acyltransferase 1 (DGAT1) in lipolysis and autophagy of adipose tissue from ketotic dairy cows.

Article

作者: Qiushi Xu ; Yunhui Fan ; John Mauck ; Juan J Loor ; Xudong Sun ; Hongdou Jia ; Xinwei Li ; Chuang Xu

High-yielding dairy cows in early lactation often encounter difficulties in meeting the energy requirements essential for maintaining milk production. This is primarily attributed to insufficient dry matter intake, which consequently leads to sustained lipolysis of adipose tissue. Fatty acids released by lipolysis can disrupt metabolic homeostasis. Autophagy, an adaptive response to intracellular environmental changes, is considered a crucial mechanism for regulating lipid metabolism and maintaining a proper cellular energy status. Despite its close relationship with aberrant lipid metabolism and cyto-lipotoxicity in animal models of metabolic disorders, the precise function of diacylglycerol o-acyltransferase 1 (DGAT1) in bovine adipose tissue during periods of negative energy balance (NEB) is not fully understood. Particularly regarding its involvement in lipolysis and autophagy. The objective of the present study was to assess the impact of DGAT1 on both lipolysis and autophagy in bovine adipose tissue and isolated adipocytes. Adipose tissue and blood samples were collected from cows diagnosed as clinically ketotic (n = 15) or healthy (n = 15) following a veterinary evaluation based on clinical symptoms and serum concentrations of BHB, which were 3.19 mM (interquartile range = 0.20) and 0.50 mM (interquartile range = 0.06), respectively. Protein abundance of DGAT1 and phosphorylation levels of unc-51-like kinase 1 (ULK1), were greater in adipose tissue from cows with ketosis, whereas phosphorylation levels of phosphoinositide 3-kinase (PI3K), protein kinase B (AKT), and mammalian target of rapamycin (mTOR) were lower. Furthermore, when adipocytes isolated from the harvested adipose tissue of 15 healthy cows were transfected with DGAT1 overexpression adenovirus or DGAT1 small interfering RNA followed by exposure to epinephrine (EPI), it led to greater ratios and protein abundance of phosphorylated hormone-sensitive triglyceride lipase (LIPE) to total LIPE and adipose triglyceride lipase (ATGL), while inhibiting the protein phosphorylation levels of ULK1, PI3K, AKT and mTOR. Overexpression of DGAT1 in EPI-treated adipocytes reduced lipolysis and autophagy, whereas silencing DGAT1 further exacerbated EPI-induced lipolysis and autophagy. Taken together, these findings indicate that upregulation of DGAT1 may function as an adaptive response to suppress adipocytes lipolysis, highlighting the significance of maintaining metabolic homeostasis in dairy cows during periods of NEB.

项与 LIPE 相关的新闻（医药）

2023-08-24

·PRNewswire

Vice Health and Wellness Signs Letter of Intent to Advance Scientific Technology Solutions for Weight Loss and Obesity

VANCOUVER, BC, Aug. 24, 2023 /PRNewswire/ - Vice Health and Wellness Inc. (CSE: VICE) (FSE: Z24) (OTC Pink: VICFF) is excited to announce the signing of a Letter of Intent ("LOI") with Biologic Pharmamedical Research Ltd to initiate a collaborative product research and development partnership for weight-loss and obesity focused products. The purpose of the LOI is to express mutual interest in developing cutting-edge nutraceutical technology products that aim to revolutionize health categories through effective and science-based innovations. It is anticipated that this LOI will lead to the establishment of a definitive agreement outlining the specific terms, conditions, and responsibilities of both VICE and Biologic Pharmamedical. During the period of the LOI the Company has agreed to cover certain expenditures which are not to exceed $10,000. Biologic Pharmamedical Research, a trailblazer in the realm of pharmacology and natural therapeutic agents, will focus on mapping the pharmacology of natural therapeutic agents to better understand poly-pharmacology at the proteomic and genomic level. VICE is committed to enhancing people's lives by offering innovative and effective health products targeting weight-loss and obesity At the core of this partnership is THERMOGALLATE™, an exclusive and patent-pending technology fully owned by Biologic. It is a unique and ground-breaking technology that facilitates efficient fat metabolism and energy production. Unlike traditional keto-products, THERMOGALLATE™ capitalizes on the body's natural fat stores to induce ketogenesis, fostering sustainable weight management and heightened cognitive function. This technology triggers the activation of Brown Adipose Fat (BAT) and Hormone Sensitive Lipase (HSL), initiating a chain reaction that enhances fat burning and release for fuel. Through this innovative process, heat and energy are generated, reducing the reliance on physical exercise alone. The key reported benefits of THERMOGALLATE™ include: Activation of Brown Adipose Fat (BAT): Facilitates efficient fat burning. Initiation of Hormone Sensitive Lipase (HSL) Activity: Breaks down and mobilizes fat for energy. Induction of Ketogenesis: Offers an alternate brain fuel source during low-caloric intake. Enhanced Energy and Cognitive Performance: Elevates energy levels, creativity, and cognitive function. Reduced Hunger Cravings and Dietary Control: Supports appetite management and dietary adherence. The partnership will encompass the creation of products with Thermogallate™ that contribute to improved lean body mass to fat mass proportions beginning with the research and development of a Gummy Version. Biologic Pharmamedical will explore the possibilities of a gummy version of the Brown Adipose Tissue activator, catering to consumers seeking a delightful and enjoyable means of experiencing the potential health benefits of the product. The company plans to explore further uses of Thermogalallate™ in consumer health products. Biologic Pharmamedical will play a crucial role in supporting the marketing efforts for these Nutraceutical Technology products. Biologic Pharmamedical will provide scientific backing, literature, and relevant research findings to substantiate health claims associated with the products. Furthermore, Biologic Pharmamedical will assist Vice Health and Wellness in organizing digital seminars or speaking engagements to disseminate vital information about the products. In addition, Vice Health and Wellness supplements will be enriched with Glyvia™, a patented and Health Canada approved natural product. Glyvia™ presents a plant-based, zero-calorie sweetness that emulates the flavor of sugar without the commonly associated bitter aftertaste found in alternative sweeteners like stevia. This proprietary complex, composed of aminoacetic acid and plant glycosides, enhances mouthfeel, sweetness, and sweet/sour balance, delivering an appealing and satisfying sensory experience. Maciej Lis, Chief Executive Officer of Vice, stated, "The collaboration between Biologic Pharmamedical Research and Vice holds tremendous potential and aligns with our shared goals of promoting health and wellness to help consumers achieve the pursuit of optimal wellness. We are excited about the possibilities and eagerly look forward to further discussions and negotiations to formalize this partnership." Franco Cavaleri BSc PhDc, Founder and CEO of Biologic, noted, "We're thrilled to partner with VICE's like-minded team to tackle weight loss and obesity through our advanced technologies led by THERMOGALLATE™. This patented technology, dubbed the 'Natural GLP1 agonist and Brown Fat Thermogenic inducer,' aims to regulate blood glucose and activate fat metabolism. This leads to spontaneous weight management and increased energy by revitalizing the body's natural fat-utilizing systems. For further information and updates, please visit the newly updated investor website at About Biologic Pharmamedical Research Biologic Pharmamedical Research is dedicated to cutting-edge research and development in the health and wellness industry. The company focuses on mapping the pharmacology of natural therapeutic agents to engineer more reliable and efficacious outcomes for consumers. About Vice Health and Wellness Inc. Vice Health and Wellness Inc. is a dynamic publicly traded company dedicated to fostering healthier lifestyle choices by offering a diverse range of products that empower consumers to enhance their mental and physical well-being. As an ever-growing community of like-minded individuals and organizations, we believe in the power of collective small steps leading to remarkable transformations. Our product line features low-sugar, plant-based gummy products, and we are actively spearheading innovations in alignment with emerging trends in the health and wellness sector. By prioritizing weight loss and harnessing the potential of AI-powered health and wellness applications, which leverage state-of-the-art artificial intelligence algorithms, we aim to provide individuals with unparalleled advice, personalized recommendations, unwavering support, and transformative solutions on their journey to ultimate well-being. Our exceptional applications intend to offer a multitude of treatment benefits, empowering users to embark on a transformative path toward optimal health. Neither the Canadian Securities Exchange nor its Regulation Services Provider (as that term is defined in the policies of the Canadian Securities Exchange) accepts responsibility for the adequacy or accuracy of this release. Forward Looking Statements Certain information set forth in this news release may contain forward-looking statements that involve substantial known and unknown risks and uncertainties. All statements other than statements of historical fact are forward-looking statements, including, without limitation, statements regarding future financial position, business strategy, use of proceeds, corporate vision, proposed acquisitions, partnerships, joint- ventures and strategic alliances and co-operations, budgets, cost and plans and objectives of or involving the Company. Such forward-looking information reflects management's current beliefs and is based on information currently available to management. Often, but not always, forward-looking statements can be identified by the use of words such as "plans", "expects", "is expected", "budget", "scheduled", "estimates", "forecasts", "predicts", "intends", "targets", "aims", "anticipates" or "believes" or variations (including negative variations) of such words and phrases or may be identified by statements to the effect that certain actions "may", "could", "should", "would", "might" or "will" be taken, occur or be achieved. A number of known and unknown risks, uncertainties and other factors may cause the actual results or performance to materially differ from any future results or performance expressed or implied by the forward-looking information. These forward-looking statements are subject to numerous risks and uncertainties, certain of which are beyond the control of the Company including, but not limited to, the impact of general economic conditions, industry conditions and dependence upon regulatory approvals. Readers are cautioned that the assumptions used in the preparation of such information, although considered reasonable at the time of preparation, may prove to be imprecise and, as such, undue reliance should not be placed on forward- looking statements. The Company does not assume any obligation to update or revise its forward-looking statements, whether as a result of new information, future events, or otherwise, except as required by securities laws. SOURCE Vice Health And Wellness Inc.

2022-10-20

·生物谷

汤其群/郭亮团队发现促进脂肪燃烧的酶Cdo1，并解析其作用机制

该研究发现，脂肪组织Cdo1受到寒冷诱导上调，能够通过PPARγ/Med24/lipolysis信号通路，转录激活脂解基因ATGL和HSL的表达，从而增加小鼠脂肪组织脂解、寒冷耐受能力和能量消耗脂肪组织分为三种类型，其中白色脂肪负责储存能量，棕色和米色脂肪可以将营养物质代谢产生的能量以热能的形式释放，用于维持体温。诱导棕色脂肪和米色脂肪的激活，可以增加机体能量消耗，是抵抗肥胖的有效策略。在寒冷条件下，机体激活脂肪组织的脂肪分解（脂解）过程，分解甘油三酯产生甘油和游离脂肪酸，为整个适应性产热过程提供能量代谢的底物。一些游离脂肪酸还能作为配体，激活PPARα等核受体的功能，进而促进产热相关基因、脂肪酸氧化基因的表达，激活米色脂肪和棕色脂肪功能。ATGL（由Pnpla2编码）是催化甘油三酯分解第一步反应的限速酶。脂肪组织特异性敲除ATGL的小鼠更容易发生肥胖，寒冷耐受能力严重受损，同时伴随棕色脂肪的白色样改变。 HSL（由Lipe编码）负责催化甘油三酯分解的第二步反应。增加小鼠脂肪组织HSL的活性抑制了高脂饮食诱导的肥胖、胰岛素抵抗以及肝脏脂肪变性。这说明脂肪组织脂解在调控机体适应性产热、能量代谢及影响肥胖发生发展中发挥重要作用。转录因子PPARγ可以促进ATGL和HSL的表达从而促进脂解，然而其具体调控机制尚未完全阐明。 2022年10月17日，复旦大学汤其群团队和上海体育学院郭亮团队在 Nature Metabolism 期刊合作发表了题为：Cdo1 promotes PPARγ-mediated adipose tissue lipolysis in male mice 的研究论文。该研究发现，脂肪组织Cdo1受到寒冷诱导上调，能够通过PPARγ/Med24/lipolysis信号通路，转录激活脂解基因ATGL和HSL的表达，从而增加小鼠脂肪组织脂解、寒冷耐受能力和能量消耗，进一步抵抗小鼠肥胖及代谢紊乱。研究团队为了深入研究米色/棕色脂肪激活的分子机制，分离了4℃冷暴露24小时和室温饲养小鼠的皮下脂肪组织以及分化成熟的棕色脂肪细胞（分化第6天）和前棕色脂肪细胞（-2天），进行RNA-seq检测。从中筛选鉴定出候选效应分子半胱氨酸双加氧酶1（Cysteine Dioxygenase 1，Cdo1）。与室温组小鼠/前棕色脂肪细胞组相比，小鼠冷暴露24小时皮下脂肪组织/成熟棕色脂肪细胞中Cdo1表达显著增加。进一步的研究还发现，Cdo1主要在脂肪组织的成熟脂肪细胞中表达；饥饿同样能够促进脂肪组织Cdo1表达的上调；高脂肪饮食（HFD）诱导小鼠肥胖后则导致脂肪组织Cdo1表达的下降。前人研究表明，Cdo1在小鼠脂肪组织、肝脏等器官存在较高水平的表达。Cdo1的全身性敲除小鼠出生后出现一定比例的死亡，存活下来的小鼠会表现为发育不良、骨骼弯曲、生长迟缓，这说明Cdo1对于机体的生长发育及正常生命活动十分重要。在3T3-L1脂肪细胞中，转录因子PPARγ和C/EBPα可以结合到Cdo1启动子上。这一研究提示Cdo1在脂肪组织中可能发挥着重要的功能。 Cdo1是生物体自身合成牛磺酸的关键酶。研究团队前期采用药理学手段，腹腔注射Cdo1代谢终末产物牛磺酸，发现牛磺酸可以促进小鼠脂肪组织棕色化进而抵抗肥胖，该研究工作于2019年发表在 Journal of Biological Chemistry 杂志。然而在生理条件下，Cdo1在脂肪组织发挥的具体作用及其分子机制有待深入研究。在这项研究中，研究人员采用雄性的脂肪组织特异性敲除 Cdo1小鼠（Cdo1AKO）以及脂肪组织特异性Cdo1转基因（Cdo1TG）小鼠，对上述问题进行了深入的研究。 Cdo1催化的氨基酸代谢路径研究人员发现，Cdo1AKO小鼠能量消耗降低，对寒冷刺激不耐受，脂肪组织脂解能力显著降低，棕色脂肪组织游离脂肪酸含量下降，更容易发生高脂饲料诱导的肥胖及肥胖相关的代谢紊乱（胰岛素抵抗、血脂异常、脂肪肝等）。RNA-seq显示，Cdo1AKO小鼠皮下脂肪组织脂解信号通路相关基因下调最为明显。然而Cdo1AKO小鼠脂肪组织牛磺酸没有明显变化，这可能是由于机体代偿性从血液循环中摄取更多的牛磺酸所致。研究团队发现Cdo1在成熟脂肪细胞核存在定位，并且Forskolin、CL316,243介导的肾上素能信号通路能够促进Cdo1的核定位。进一步研究发现Cdo1能够通过和PPARγ及Med24相互作用，促进Med24招募到脂解基因ATGL和HSL的启动子上，从而转录激活上述脂解基因的表达。Med24是Mediator Complex核心亚基之一。Mediator Complex可以促进转录前起始复合物（Preinitiation complex，PIC）的形成进而促进基因的转录。有趣的是，Cdo1酶活性缺失的突变体（Y157F）能够和野生型Cdo1一样促进Med24招募到脂解基因的启动子上并转录激活脂解基因。因此Cdo1调控脂解基因表达的功能可能不依赖于其氨基酸代谢酶的活性。此外， Cdo1TG促进雄性小鼠脂肪组织脂解，增加能量消耗及寒冷耐受能力，并抵抗高脂饲料诱导的肥胖及胰岛素抵抗等相关代谢紊乱。该研究揭示了脂肪组织Cdo1在适应性产热及维持能量代谢稳态中的重要作用，发现了Cdo1/PPARγ/Med24/Lipolysis的转录调节新路径，阐明了氨基酸代谢酶Cdo1调控脂肪代谢的新功能和新机制，为预防和治疗肥胖提供了新的思路和潜在干预靶点。 Cdo1调控脂解的模式图（图片已获BioRender授权）复旦大学基础医学院2019级博士研究生郭盈盈为论文第一作者。复旦大学基础医学院汤其群教授和上海体育学院运动健康学院郭亮教授为共同通讯作者。