n-3 PUFA derived epoxides and thermogenesis for obesity prevention

n-3 PUFA 衍生的环氧化物和产热作用用于预防肥胖

基本信息

批准号：
10438276
负责人：
Ling Zhao
金额：
$ 44.55万
依托单位：
UNIVERSITY OF TENNESSEE KNOXVILLE
依托单位国家：
美国
项目类别：
财政年份：
2022
资助国家：
美国
起止时间：
2022-04-01 至 2025-03-31
项目状态：
未结题

来源：
https://reporter.nih.gov/project-details/10438276
关键词：
2019-nCoV Acids Adipocytes Adipose tissue Adrenergic Agents Adult Affect Animal Model Animals Appearance Area Biochemical Biology Biomedical Research Blood Blood Vessels Body Temperature Body Weight Brown Fat COVID-19 severity Cardiovascular Diseases Cell Line Cell Transplantation Cells Communicable Diseases Coronavirus Cytochrome P450 Diet Differentiation and Growth Docosahexaenoic Acids Dose Dyslipidemias Eicosapentaenoic Acid Energy Metabolism Engineering Enzymes Epoxide hydrolase Epoxy Compounds Fatty Acids Fatty acid glycerol esters Fish Oils Generations Genes Glucose Glycols Goals High Fat Diet High Prevalence Human Immunocompromised Host In Vitro Inflammation Light Lipolysis Lipoxygenase Longevity Mediating Medical Care Costs Metabolic Metabolism Molecular Molecular Target Mus N-3 polyunsaturated fatty acid Non-Insulin-Dependent Diabetes Mellitus Obesity Outcome Pain Pharmacology Play Polyunsaturated Fatty Acids Process Prostaglandin-Endoperoxide Synthase Proteins Public Health Reporting Research Personnel Role Signaling Molecule Stromal Cells Supplementation Technology Thermogenesis Training Transplantation Triglycerides adipocyte biology cell growth cell type comorbidity diet-induced obesity fatty acid metabolism feeding graduate student human subject improved in vivo inhibitor insight lipid metabolism novel novel strategies obesity prevention obesity treatment oxidation prevent protein expression response side effect subcutaneous transcriptome sequencing translational study uncoupling protein 1 undergraduate student uptake

项目摘要

Project Summary/Abstract Obesity remains one of the biggest public health challenges worldwide. Obesity is associated with various comorbidities, including type 2 diabetes, dyslipidemia, and cardiovascular diseases, leading to a shorter lifespan and higher medical costs. Recent studies have indicated that obesity is also associated with the high prevalence and severity of COVID-19, an infectious disease caused by coronavirus SARS-CoV-2. Therefore, novel approaches and new generations of researchers are still needed to treat and prevent human obesity. Brown adipose tissue (BAT), a fat type responsible for non-shivering thermogenesis and now known to exist in adult humans, has emerged as a novel target to increase energy expenditure and improve systemic metabolism for obesity prevention. In addition, a browning process, i.e., the appearance of beige adipocytes within white adipose tissue (WAT) depots in response to cold or other stimulations, has also been reported. However, to our knowledge, there are still no practical and effective ways to stimulate thermogenesis in humans except for cold exposure or β-adrenergic stimulation, which is associated with side effects and low compliance. We have discovered that 17,18-epoxyeicosatetraenoic acid (EEQ, an n-3 polyunsaturated fatty acid eicosapentaenoic acid (EPA)-derived epoxy fatty acid) at a much low dose, when stabilized by a pharmacological inhibitor of soluble epoxide hydrolase (the enzyme that degrades epoxy fatty acids), significantly increased core body temperature and heat production and improved blood triglycerides and glucose levels in diet-induced obesity. The thermogenic efficacy of 17,18-EEQ is better than 19,20-epoxydocosapentaenoic acid (EDP, a docosahexaenoic acid (DHA)-derived epoxy fatty acid) and much potent than the reported EPA or fish oil enriched with EPA and DHA. Therefore, the goal of this proposal is to (Aim 1) elucidate the molecular and biochemical mechanisms by which 17,18-EEQ promotes thermogenesis in mouse brown and beige adipocytes in vitro compared with 19,20-EDP and (Aim 2) determine the efficacy of 17,18-EEQ compared with 19,20-EDP in increasing thermogenesis in human brown and beige adipocytes and increasing energy expenditure and improving metabolism in transplanted mice in vivo. In light of the critical roles of thermogenesis in human obesity treatment and prevention, it is urgent to identify novel, effective, and safe agents and molecular targets to promote thermogenesis and increase energy expenditure. The outcomes for this proposed project are (1) significant advancement of the understanding of 17,18-EEQ biology, leading to novel strategies to boost thermogenesis in brown and beige adipocytes; (2) extensive exposure and training of both undergraduate and graduate students to biomedical research in the areas of adipocyte biology and obesity.

项目摘要/摘要肥胖仍然是全球最大的公共卫生挑战之一。合并症，2型糖尿病，血脂异常和心血管疾病，导致寿命较短以及最近的研究表明。 Covid-19的严重程度，这是由SARS-COV-2引起的一种传染病方法和新一代的研究人员仍然需要治疗和预防人类肥胖脂肪组织（BAT），这是一种用于非动摇热发生的脂肪，现在已知存在于成人人类已成为增加能量消耗并改善全身代谢的新目标遵守预防。此外，褐变过程但是，还报道了我们的组织库（WAT）库知识，仍然没有实用有效的方法来刺激人类的热发生暴露或β-肾上腺素能刺激，这与我们的副作用相关发现17,18--环氧乙烯酸（多不饱和脂肪酸eicosapenoic）当通过药理学抑制剂稳定时，酸（EPA）衍生的环氧脂肪酸）是可溶性环氧化物水解酶（降解环氧脂肪酸的酶），核心体显着增加温度和热量产生，并改善饮食诱导的肥胖症中的血液甘油三酸酯和葡萄糖水平。 17,18-EEQ的热疗法优于19,20-环氧基戊烯酸（EDP，A，A 二十六烯酸（DHA）衍生的环氧脂肪酸）和报告的EPA或鱼油有效因此，富含EPA和DHA。生化机制17，18-EEQ促进小鼠棕色和米色脂肪细胞中的热发生在体外与19,20-EDP相比，（AIM 2）确定17,18-EEQ的疗效，而19,20-EDP 增加人类棕色和米色Adige的热生成，以及能量消耗和凹陷的能量消耗和根据人类肥胖症的关键作用，改善了体内移植小鼠的代谢治疗和预防，迫切需要识别新颖，有效，安全，安全的剂和分子靶标的促进热生成并增加能量消耗。对17,18-EEQ生物学的理解的显着发展，导致了新的策略来提高棕色和米色脂肪细胞的热发生；研究生从事脂肪细胞生物学和观察领域的生物医学研究。

项目成果

期刊论文数量（4）

专著数量（0）

科研奖励数量（0）

会议论文数量（0）

专利数量（0）

Tetra-Primer Amplification-Refractory Mutation System (ARMS)-PCR for Genotyping Mouse Leptin Gene Mutation.

DOI：
10.3390/ani12192680
发表时间：
2022-10-05
期刊：
Animals : an open access journal from MDPI
影响因子：
0
作者：
通讯作者：

Impact of Paraben Exposure on Adiposity-Related Measures: An Updated Literature Review of Population-Based Studies.

DOI：
10.3390/ijerph192316268
发表时间：
2022-12-05
期刊：
INTERNATIONAL JOURNAL OF ENVIRONMENTAL RESEARCH AND PUBLIC HEALTH
影响因子：
0
作者：
Xu, Xinyun;Wu, Haoying;Terry, Paul D.;Zhao, Ling;Chen, Jiangang
通讯作者：
Chen, Jiangang

Detecting fa leptin receptor mutation in Zucker rats with tetra-primer amplification-refractory mutation system (ARMS)-PCR.

DOI：
10.1016/j.heliyon.2023.e20159
发表时间：
2023-09
期刊：
HELIYON
影响因子：
4
作者：
Xu, Xinyun;Hu, Xinge;Ma, Guodong;Wang, Tiannan;Wu, Jayne;Zhu, Xiaojuan;Chen, Guoxun;Zhao, Ling;Chen, Jiangang
通讯作者：
Chen, Jiangang

Reciprocal Effect of Environmental Stimuli to Regulate the Adipogenesis and Osteogenesis Fate Decision in Bone Marrow-Derived Mesenchymal Stem Cells (BM-MSCs).