通过AKT激活,ADGRL4诱导脂肪色和体重减轻
Longyun Hu1, Ze-Wei Zhao1, Qian Wu1
1Shenzhen Key Laboratory of Systems Medicine for Inflammatory Diseases & Department of Biochemistry, School of Medicine, Sun Yat-sen University, Shenzhen, 518107, China.
Molecular and cellular endocrinology
|February 25, 2026
概括
粘附G蛋白结合受体L4 (ADGRL4) 激活促进色脂肪组织的发展,并对抗肥胖. 这种GPCR增强了能量消耗和代谢平衡,为代谢障碍提供了一个新的治疗点.
科学领域:
- 代谢信号和内分泌学
- 脂肪组织生物学 脂肪组织生物学
- G蛋白结合受体研究研究
背景情况:
- 棕色和色脂肪组织对于能量消耗和代谢平衡至关重要.
- G蛋白结合受体 (GPCRs) 介导适应性热生成和脂肪色.
- 在小鼠中,β3-上腺受体 (β3-AR) 是关键的,但在人类脂肪细胞中是有限的,因此需要新的治疗点.
研究的目的:
- 为了确定诱导脂肪色的新型GPCR标.
- 研究粘附G蛋白结合受体L4 (ADGRL4) 在调节脂肪组织代谢中的作用.
- 评估ADGRL4作为肥胖和代谢功能障碍的潜在治疗标.
主要方法:
- 在ADGRL4激活后的脂肪细胞分化和UCP1表达的体外研究.
- 在小鼠体内实验 (正常和高脂肪饮食) 评估ADGRL4对色脂肪发育和代谢参数的影响.
- 对下游信号通路的机制研究,包括AKT酸化和UCP1调节.
主要成果:
- 在体外ADGRL4激活促进了色脂肪细胞的分化,上调了UCP1和减少了脂质积累.
- 在体内,ADGRL4在小鼠中诱导了色脂肪,没有系统性影响.
- 在高脂肪饮食养的小鼠中ADGRL4的激活减少了体重,脂肪沉积和改善了葡萄糖不耐受性.
- 在机械上,ADGRL4增强了AKT酸化,激活了p-AKT/UCP1轴以驱动色.
结论:
- ADGRL4是诱导脂肪色和打击肥胖的一个有希望的分子标.
- 通过增加能量消耗,ADGRL4激活为代谢障碍提供了潜在的治疗策略.
- p-AKT/UCP1信号轴调解ADGRL4对脂肪组织代谢的有益作用.
相关概念视频
cAMP-dependent Protein Kinase Pathways
8.7K
Cyclic Adenosine Monophosphate (cAMP) is an essential second messenger that activates protein kinase A (PKA) and regulates various biological processes. A single epinephrine molecule binds to GPCR and activates several heterotrimeric G proteins, each stimulating multiple adenylyl cyclase, amplifying the signal, and synthesizing large numbers of cAMP molecules. Small changes in cAMP concentration affect PKA activity. The binding of four cAMP molecules induces a conformational change in PKA,...
8.7K
PI3K/mTOR/AKT Signaling Pathway
5.9K
The mammalian target of rapamycin (mTOR) is a serine/threonine kinase that regulates growth, proliferation, and cell survival in response to hormones, growth factors, or nutrient availability. This kinase exists in two structurally and functionally distinct forms: mTOR complex 1 (mTORC1) and mTOR complex 2 (mTORC2). The first form (mTORC1) is composed of a rapamycin-sensitive Raptor and proline-rich Akt substrate, PRAS40. In contrast, mTORC2 consists of a...
5.9K
GPCRs Regulate Adenylyl Cylase Activity
7.8K
Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of...
7.8K
Glucagon-like Receptor Agonists
1.1K
Incretins include glucagon-like peptide-1 (GLP-1) and glucose-dependent insulinotropic polypeptide (GIP), which stimulate insulin secretion post-meals. In type 2 diabetes, GIP's efficacy is reduced, making GLP-1 a viable drug target. GIP originates from preproGIP.
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
GLP-1, when administered in high doses intravenously, triggers insulin secretion, inhibits glucagon release, slows gastric emptying, reduces food intake, and restores normal insulin secretion. However, its rapid inactivation by...
1.1K
Regulation of Food Intake
3.0K
Short-term regulation of food intake primarily involves neural signals from the gastrointestinal (GI) tract, blood nutrient levels, and GI tract hormones. Communication between the gut and brain via vagal nerve fibers plays a significant role in evaluating the contents of the gut. Clinical studies have shown that protein ingestion produces a more prolonged response in these nerve fibers compared to an equivalent amount of glucose. Additionally, the activation of stretch receptors caused by GI...
3.0K


