Diagnostic value of methylated branched chain amino acid transaminase 1/IKAROS family zinc finger 1 for colorectal cancer

BACKGROUND The diagnostic value of combined methylated branched chain amino acid transaminase 1(BCAT1)/IKAROS family zinc finger 1(IKZF1)in plasma for colorectal cancer(CRC)has been explored since 2015.Recently,several related studies have published their results and showed its diagnostic efficacy.AIM To analyze the diagnostic value of methylated BCAT1/IKZF1 in plasma for screening and postoperative follow-up of CRC.METHODS The candidate studies were identified by searching the PubMed,Embase,Cochrane Library,CNKI,and Wanfang databases from May 31,2003 to June 1,2023.Sensitivity,specificity,and diagnostic accuracy were calculated by merging ratios or means.RESULTS Twelve eligible studies were included in the analysis,involving 6561 participants.The sensitivity of methylated BCAT1/IKZF1 in plasma for CRC diagnosis was 60%[95%confidence interval(CI)53-67]and specificity was 92%(95%CI:90-94).The positive and negative likelihood ratios were 8.0(95%CI:5.8-11.0)and 0.43(95%CI:0.36-0.52),respectively.Diagnostic odds ratio was 19(95%CI:11-30)and area under the curve was 0.88(95%CI:0.85-0.91).The sensitivity and specificity for CRC screening were 64%(95%CI:59-69)and 92%(95%CI:91-93),respectively.The sensitivity and specificity for recurrence detection during follow-up were 54%CONCLUSION The detection of methylated BCAT1/IKZF1 in plasma,as a non-invasive detection method of circulating tumor DNA,has potential CRC diagnosis,but the clinical application prospect needs to be further explored.

Branched-chain amino acids in liver diseases

Branched chain amino acids(BCAAs)have been shown to affect gene expression,protein metabolism,apoptosis and regeneration of hepatocytes,and insulin resistance.They have also been shown to inhibit the proliferation of liver cancer cells in vitro,and are essential for lymphocyte proliferation and dendritic cell maturation.In patients with advanced chronic liver disease,BCAA concentrations are low,whereas the concentrations of aromatic amino acids such as phenylalanine and tyrosine are high,conditions that may be closely associated with hepatic encephalopathy and the prognosis of these patients.Based on these basic observations,patients with advanced chronic liver disease have been treated clinically with BCAA-rich medicines,with positive effects.

Impairment of innate immune responses in cirrhotic patients and treatment by branched-chain amino acids

It has been reported that host defense responses, such as phagocytic function of neutrophils and natural killer (NK) cell activity of lymphocytes, are impaired in cirrhotic patients. This review will concentrate on the impairment of innate immune responses in decompensated cirrhotic patients and the effect of the treatment by branched-chain amino acids (BCAA) on innate immune responses. We already reported that phagocytic function of neutrophils was significantly improved by 3-mo BCAA supplementation. In addition, the changes of NK activity were also significant at 3 mo of supplementation compared with before supplementation. Also, Fisher’s ratios were reported to be significantly increased at 3 mo of BCAA supplementation compared with those before oral supplementation. Therefore, administration of BCAA could reduce the risk of bacterial and viral infection in patients with decompensated cirrhosis by restoring impaired innate immune responses of the host. In addition, it was also revealed that BCAA oral supplementation could reduce the risk of development of hepatocellular carcinoma in cirrhotic patients. The mechanisms of the effects will also be discussed in this review article.

Synergistic renoprotective effect of a compiled branched-chain amino acids and Cymbopogon schoenanthus extract against experimentally induced oxido-nitrosative renal insult

Objective: To better investigate the protective role of branched-chain amino acids(BCAAs)and Cymbopogon schoenanthus(CS) extract against the potassium dichromate(PDC)-induced oxido-nitrosative nephrotoxic insult in the experimental rat model. Methods: Thirty male rats were randomly divided into five equal groups: The 1 st group served as control; the 2^(nd)was injected with a single dose of PDC(15 mg/kg b.w i.p.);the 3^(rd), 4^(th), and 5^(th) groups were respectively treated with BCAAs, CS, and their combination for 15 d prior to induction of renal insult via PDC single dose(15 mg/kg b.w s.c.). The experimental period was terminated in all groups 2 d after induction of renal insult. The harvested kdney samples were divided for biochemical assays and histological examination. Results: The PDC-induced nephrotoxic effect caused a depletion of renal oxidative scavengers glutathione, superoxide dismutase with consequent lipo-oxidative cellular membrane deterioration manifested by a rise in malonaldehyde, oxidized glutathione, myeloperoxidase and the concomitant increase in inflammatory response elements tumor necrosis factor α, nitric oxide, and interleukin 1 β.Moreover, the comet assay and increased 8-hydroxy-2-deoxyguanosine proved an accelerated apoptotic DNA fragmentation. These local renal changes were met with global altered blood biochemistry. The BCAAs and CS or their compiled administration showed an ameliorative effect against PDC-induced nephrotoxic in a synergistic pattern. Conclusions: Both BCAAs and CS or their combined administration afford potential competitors against renal insult induced by polyvalent anion pollutants in experimentally studied animals model. As a route for novel drug discovery, further investigation should be attempted to optimize their augmenting reno-protecting potential.

Effect of branched-chain amino acids in patients receiving intervention for hepatocellular carcinoma

AIM: To investigate the usefulness of branched-chain amino acids (BCAA) before transarterial chemoembolization (TACE) or radiofrequency ablation (RFA).

Herbicide-Resistant Mutations in Acetolactate Synthase Can Reduce Feedback Inhibition and Lead to Accumulation of Branched-Chain Amino Acids

The branched-chain amino acids (BCAAs) valine, leucine and isoleucine are essential amino acids that are critical for animal growth and development. Animals need to obtain BCAAs from their diet because they cannot synthesize them. Plants are the ultimate source of these amino acids. Acetolactate synthase (ALS) is the first common enzyme in the biosynthesis of BCAAs. The metabolic control of BCAA biosynthesis involves allosteric regulation of ALS by the end-products of the pathway, i.e., valine, leucine and isoleucine. ALS holoenzyme seems to consist of two large catalytic subunits and two small regulatory subunits. In a previous study, using homologous recombination dependent gene targeting we created rice plants in which W548Land S627I mutations were induced into the endogenous gene encoding the ALS catalytic subunit. These two amino acid substitutions conferred hypertolerance to the ALS-inhibiting herbicide bispyripac-sodium. In this study, we revealed that feedback regulation by valine and leucine was reduced by these two amino acid substitutions. Furthermore, in leaves and seeds of ALS mutants with W548Land/or S627I substitution, a 2- to 3-fold increase in BCAAs was detected. Our results suggest that the ALS catalytic subunit is also involved in feedback regulation of ALS, and that judicious modification of the regulatory and catalytic subunits of ALS-coding genes by gene targeting can lead to the efficient accumulation of BCAA in plants.

OPTICALLY ACTIVE AMINO ACIDS WITH HIGHLY BRANCHED SIDE CHAIN (I) SYNTHESIS OF D- AND L- 2-AMINO-5,5-DIMETHYLHEXANOIC ACID AND 2-AMINO-6,6-DIMETHYLHEPTANOIC ACID

The title compounds were prepared by the enzymatic resolution of the corresponding N-acetylated DL-amino acids methyl esters, which were obtained from t-butyl chloride via an 8-step synthesis.

Functional microbiomics reveals branched-chain amino acids depletion for alleviation of insulin resistance by berberine

Increased circulating branched-chain amino acids(BCAAs)have been involved in the pathogenesis of obesity and insulin resistance.However,evidence relating berberine(BBR),gut microbiota,BCAAs,and insulin resis⁃tance is limited.Here,we showed that BBR could effectively rectify steatohepatitis and glucose intolerance in high-fat diet(HFD)-fed mice.BBR reorganized gut microbiota populations under both the normal chow diet(NCD)and HFD.Particu⁃larly,BBR noticeably decreased the relative abundance of BCAA-producing bacteria,including order Clostridiales;fami⁃lies Streptococcaceae,Clostridiaceae,and Prevotellaceae;and genera Streptococcus and Prevotella.Compared with the HFD group,predictive metagenomics indicated a reduction in the proportion of gut microbiota genes involved in BCAA biosynthesis but the enrichment genes for BCAA degradation and transport by BBR treatment.Accordingly,the elevated serum BCAAs of HFD group were significantly decreased by BBR.Furthermore,the Western blotting results implied that BBR could promote the BCAA catabolism in the liver and epididymal white adipose tissues of HFD-fed mice by acti⁃vation of the multienzyme branched-chain α-ketoacid dehydrogenase complex,whereas by inhibition of the phosphoryla⁃tion state of BCKDHA(E1α subunit)and branched-chain α-ketoacid dehydrogenase kinase.The ex vivo assay further confirmed that BBR could increase BCAA catabolism in both AML12 hepatocytes and 3T3-L1 adipocytes.Finally,data from healthy subjects and diabetics confirmed that BBR could improve glycemic control and modulate circulating BCAAs.Besides,functional microbiomics integrated high-throughput microbial genomics,metabolomics and molecular biotechnology has also been successfully applied to reveal the anti-obesity mechanism of hydroxysafflor yellow A.

支链氨基酸转氨酶1在食管鳞癌中的表达及其临床意义

目的探讨食管鳞癌(ESCC)患者癌组织中支链氨基酸转氨酶1(BCAT1)的表达及临床意义。方法采用qRT-PCR和Western blot技术检测食管鳞癌细胞系中BCAT1基因的表达水平,筛选出合适的食管癌细胞,作为后续研究。敲低和过表达BCAT1,采用Western blot检测ESCC细胞中BCAT1的蛋白表达水平。CCK-8活力测定、克隆形成实验、划痕实验、Transwell检测ESCC细胞增殖、迁移和侵袭等细胞表型的变化。结果qRT-PCR和Western blot结果显示,与正常细胞相比,BCAT1在ESCC中的相对表达量降低,尤其是KYSE150和Eca109细胞更为明显,因此选择这两株细胞进行研究。CCK-8细胞增殖实验结果显示,细胞在转染BCAT1 siRNA 48 h后,其增殖率明显高于对照组;而过表达BCAT1之后,效果则相反。克隆形成实验结果表明,BCAT1的敲低显著促进ESCC细胞的克隆形成,而BCAT1的过表达显著抑制ESCC细胞的克隆形成。细胞划痕实验和Transwell实验结果表明,与Control siRNA组相比,BCAT1 siRNA组ESCC细胞的迁移和侵袭明显升高;而过表达组中ESCC细胞的迁移和侵袭明显受到抑制。结论BCAT1在ESCC中低表达,BCAT1低表达显著促进ESCC细胞增殖、迁移和侵袭。

BCAT1抑制剂BAY-069的合成工艺优化

BAY-069是目前体外活性最强的支链氨基酸转氨酶1(BCAT1)抑制剂,但其报道的合成路线存在原料成本较高、总收率极低和中间体结构表征不充分等缺点。本研究基于已有合成路线,重点对其合成工艺中的Ullmann偶联反应进行了系统优化。以1-硝基萘(1)为起始原料,经过7步反应和手性色谱柱手性拆分合成目标化合物BAY-069。所有中间体和目标化合物均经1 H NMR,13 C NMR和HR-MS表征。以Ullmann偶联反应为主要优化步骤的路线,其优化后的总收率为11.0%(3b→(±)-BAY-069),是原总收率1.6%(3a→(±)-BAY-069)的6.9倍。

BCAT1作为胰腺导管腺癌潜在诊断标志物的临床应用价值研究

目的 本研究拟验证前期研究发现的bcat1基因表达产物支链氨基酸转氨酶1(BCAT1)作为胰腺导管腺癌潜在血清学诊断标志物的临床应用价值。方法 收集临床PDAC患者血清样本作为实验组,收集胃癌、肝癌、结直肠癌、慢性胰腺炎患者及健康人群血清样本作为对照,采用酶联免疫吸附实验(ELISA)检测血清样本BCAT1浓度,验证其作为标志物的临床诊断价值。结果 ELISA结果显示PDAC组患者血清BCAT1浓度显著高于健康对照组,差异有统计学意义(P<0.05,U=1 206)。PDAC组患者血清BCAT1浓度高于慢性胰腺炎组,差异有统计学意义(P<0.05,H=33.80);与其他消化道肿瘤相比,高于肝癌组和结直肠癌组,差异有统计学意义(P<0.05,H=33.80),与胃癌组差异无统计学意义(P>0.05,H=33.80)。BCAT1与CA19-9的相关性较好,且差异有统计学意义(P<0.05,R^(2)=0.080 52),与CEA(R^(2)=2.265e-005)、CA125(R^(2)=0.025 88)和CA72-4(R^(2)=0.007 7)相关性较低,差异无统计学意义(P>0.05);BCAT1诊断PDAC的AUC优于CA72-4,与CA125和CEA相当,劣于CA19-9;BCAT1 cut off值为1.556ng/mL,敏感度为64.1%,特异度为80%。BCAT1在PDAC早中期患者血清浓度中位数为0.283 ng/mL,晚期患者升高为0.482 ng/mL,差异有统计学意义(P<0.05,U=1029);在肿瘤≥40 mm(U=641)、中低分化(U=435)、胰头部位(H=2.767)均表现为表达水平升高,差异无统计学意义(P均>0.05)。动态观测的BCAT1浓度在第0天和1~30天(U=44)、31~60天和61~90天(U=36)浓度差异有统计学意义(P均<0.05)。结论 BCAT1作为潜在的血清学标志物,对于PDAC的鉴别诊断、肿瘤分期、疾病进展判断具有参考价值,是目前现有的PDAC血清标志物的有益补充。

Plasma Levels of Amino Acids in Japanese Men and Their Changes after the Administration of Glucose and Sucrose

Background: It is not known whether plasma amino acids levels are different between young and old men in Japan. No research has been reported about changes in plasma levels of amino acids after the administration of glucose or sucrose to young and aged men. Objective: We want to know whether there are age differences in plasma levels of amino acids and if the administration of glucose or sucrose influences their levels. Results: Old people had lower plasma levels of most of amino acids, especially essential and branched-chain amino acids than young men. Plasma levels of amino acids were measured after the administration of 50 grams of glucose or sucrose to young (18 - 22 years old) and aged (≥50 years old) male adults. Plasma levels of total amino acids decreased after the administration of glucose. Decrease in the total amino acid levels was significant in aged men after the administration of sucrose. A significant decrease in plasma levels of total non-essential amino acids was observed at 120 min after the administration of glucose but not sucrose in both aged and young men. Both glucose and sucrose administrations resulted in a significant decrease in the plasma levels of the total essential amino acid levels and branched amino acids in young and aged men. Conclusion: These results suggest that there are age differences in plasma levels of amino acids. Upon the administration of glucose or sucrose amino acids, particularly essential amino acids, decreased in plasma. These amino acids may be transported from the blood soon after the administration of sugar (glucose or sucrose) to the tissues, such as muscles, possibly due to an increase in the insulin levels.

支链氨基酸转移酶1在肿瘤发生与进展中的作用机制

支链氨基酸转移酶1(branched-chain amino acid transaminase 1,BCAT1)催化支链氨基酸(branched-chain amino acids,BCAA)和支链酮酸(branched-chain keto acids,BCKA)之间的转换反应,在维持二者稳态中发挥重要作用。近年来人们发现,BCAT1在多种恶性肿瘤中高表达,且与癌症的分期和预后关系密切,进一步研究证实,BCAT1能促进癌细胞的增殖、侵袭和转移,并揭示BCAT1在癌症发生发展中的部分作用机制:(1)不同肿瘤中BCAT1催化转氨基反应的方向不同,BCAT1既可催化BCAA分解为BCKA,也可催化BCKA合成BCAA,这两个方向都可能促进癌症的发生和发展;(2)BCAT1既能直接影响肿瘤细胞代谢来发挥相关作用,也能通过影响肿瘤微环境而产生促癌效应。总体而言,BCAT1通过催化BCAA的分解与合成反应,影响物质代谢、能量合成、信号通路、肿瘤免疫、表观遗传学和细胞周期等方面,进而促进癌症的发生与进展。本文就国内外BCAT1和BCAA的研究进展,聚焦BCAT1在肿瘤发生发展中的作用机制做一综述,为进一步探讨BCAT1在恶性肿瘤研究中的应用前景提供理论依据。

支链氨基酸有效预测慢性阻塞性肺病的急性加重

目的:探讨支链氨基酸(BCAAs)代谢在慢性阻塞性肺病(COPD)发生机制中的作用。方法:收集42例COPD稳定期患者纳入COPD组,40例COPD急性加重(AECOPD)期患者纳入AECOPD组,收集同期46例健康体检者为对照组,采集外周血,应用液相色谱-质谱分析检测BCAAs水平,酶联免疫吸附(ELISA)法检测炎症因子水平,并对二者的相关性进行分析。结果:与对照组比较,COPD组及AECOPD组患者血浆亮氨酸、缬氨酸水平更低,且AECOPD组低于COPD组;血浆白介素(IL)-8、C-反应蛋白(CRP)水平更高,且AECOPD组高于COPD组(P均<0.001)。血浆中亮氨酸、缬氨酸水平与IL-8、CRP水平呈负相关(r=-0.64、-0.71、-0.73、-0.73,P均<0.05)。结论:BCAAs代谢可能通过炎症反应参与COPD的发生,临床中BCAAs水平有可能成为检测COPD急性加重潜在的生物标志物。

支链氨基酸代谢与2型糖尿病关系的研究进展

支链氨基酸(BCAAs)是一类因存在脂肪烃链而得名的必需氨基酸,包括亮氨酸、异亮氨酸以及缬氨酸。BCAAs同胰岛素抵抗的关系于1964年被提出,该类氨基酸在膳食中常见,其循环水平通过对糖脂代谢和胰岛素分泌的调控对2型糖尿病(T2DM)病程发展起着重要的作用。作为一种发病率高、并发症严重的慢性代谢性疾病,糖尿病已经对全球人民生活生产造成了极大的困扰。其中T2DM作为糖尿病中占比最高的类型,正大幅度降低患者的生活质量。本文通过糖脂代谢以及其他相关机制,将BCAAs代谢分解过程与T2DM发生发展联系起来,从而为临床T2DM的治疗诊断提供更多思路。

支链氨基酸代谢物对风湿性心脏瓣膜病体外循环术后低心排血量的预测价值

目的:探讨支链氨基酸代谢物对风湿性心脏瓣膜病病人行体外循环术后发生低心排血量事件的预测价值。方法:选取2019年1月—2022年1月我院收治的风湿性心脏瓣膜病病人154例作为研究对象,根据体外循环术后是否出现低心排血量,将病人分为低心排血量组(52例)和非低心排血量组(102例)。对比分析两组病人情况,多因素Logistic回归分析低心排血量事件的影响因素。Cox比例风险模型调整混杂变量,分析支链氨基酸代谢物和传统标志物与低心排血量事件的关联性。GRACE风险评分探讨支链氨基酸和传统标志物结合后对低心排血量的预测能力。Cox回归评价支链氨基酸代谢物和传统标志物之间的交互作用。建立回归方程y=1-1/(1+e-z)预测模型并进行验证。结果:脑钠肽、肌钙蛋白I、亮氨酸、缬氨酸、异亮氨酸等是低心排血量事件的独立危险因素。随着脑钠肽、肌钙蛋白I、亮氨酸、缬氨酸、异亮氨酸水平的升高,与低心排血量事件的关联效应也更强。支链氨基酸代谢物和传统标志物结合,会提高GRACE风险评分对低心排血量的预测能力。异亮氨酸联合脑钠肽前体对低心排血量事件的预测效应最高。经Bootstrap自抽样,预测模型区分度、准确度较好。结论:支链氨基酸代谢物和低心排血量密切相关。支链氨基酸代谢物加入传统标志物中,会提高对低心排血量的预测能力,有助于改善风湿性心脏瓣膜病病人预后。

Enhancement of precursor amino acid supplies for improving bacitracin production by activation of branched chain amino acid transporter BrnQ and deletion of its regulator gene lrp in Bacillus licheniformis

Bacitracin,a new type of cyclic peptide antibiotic,is widely used as the feed additive in feed industry.Branched chain amino acids(BCAAs)are the key precursors for bacitracin synthesis.In this research,soybean meal was served as the raw material to supply precursor amino acids for bacitracin synthesis,and enhanced production of bacitracin was attempted by engineering BCAA transporter BrnQ and its regulator Lrp in the bacitracin industrial production strain Bacillus licheniformis DW2.Firstly,our results confirmed that Lrp negatively affected bacitracin synthesis in DW2,and deletion of lrp improved intracellular BCAA accumulations,as well as the expression level of BCAA transporter BrnQ,which further led to a 14.71%increase of bacitracin yield,compared with that of DW2.On the contrary,overexpression of Lrp decreased bacitracin yield by 12.28%.Secondly,it was suggested that BrnQ acted as a BCAA importer in DW2,and overexpression of BrnQ enhanced the intracellular BCAA accumulations and 10.43%of bacitracin yield.While,the bacitracin yield decreased by 18.27%in the brnQ deletion strain DW2△brnQ.Finally,BrnQ was further overexpressed in lrp deletion strain DW2△lrp,and bacitracin yield produced by the final strain DW2△lrp::BrnQ was 965.34 U/mL,increased by 22.42%compared with that of DW2(788.48 U/mL).Collectively,this research confirmed that Lrp affected bacitracin synthesis via regulating the expression of BCAA transporter BrnQ and BCAA distributions,and provided a promising strain for industrial production of bacitracin.

支链氨基酸的生理功能及其在反刍动物生产中的应用研究进展

支链氨基酸是维持动物机体生长发育、生命活动和生理功能的必需氨基酸。支链氨基酸由于其特殊的分子结构而具有特殊生理功能。近年来研究发现,支链氨基酸具有氧化供能、调节蛋白质代谢、调节脂肪代谢、调节激素分泌、调节免疫、缓解氧化应激等多种功能。本文综述了支链氨基酸的生理功能及其在反刍动物生产中的应用,旨在为支链氨基酸在反刍动物生产中的合理应用提供理论依据和参考。

Supplementation of branched-chain amino acids in protein-restricted diets modulates the expression levels of amino acid transporters and energy metabolism associated regulators in the adipose tissue of growing pigs

This experiment was conducted to investigate the effects of branched-chain amino acids(BCAA)supplemented in protein-restricted diets on the growth performance and the expression profile of amino acid transporters and energy metabolism related regulators in the white adipose tissue(WAT)of different regional depots including dorsal subcutaneous adipose(DSA) and abdominal subcutaneous adipose(ASA), A total of 24 crossbred barrows(7.40 ± 0.70 kg) were randomly divided into 4 groups and were fed the following isocaloric diets for 33 days: 1) a recommended adequate protein diet(AP, 20% CP, as a positive control); 2) a low protein diet(LP, 17% CP); 3) the LP diet supplemented with BCAA(LP + B, 17% CP) to reach the same level of the AP diet group; 4) the LP diet supplemented with 2 times the amount of BCAA(LP + 2B, 17% CP). The daily gain and daily feed intake of the LP diet group were the lowest among all the treatments(P < 0.01). The feed conversion was improved markedly in the group of LP + B compared with the LP diet group(P < 0.05). No significant difference was noted for the serum biochemical parameter concentrations of glucose, triglyceride, nonesterified fatty acid and insulin among the groups(P > 0.05). Moreover, BCAA supplementation down-regulated the expression levels of amino acid transporters including L-type amino acid transporter 1 and sodium-coupled neutral amino acid transporter 2 in DSA, but up-regulated the expression level of Ltype amino acid transporter 4 in ASA(P < 0.05), Meanwhile, the energy sensor AMP-activated protein kinase α was activated in the DSA of pigs fed LP diet and in the ASA of the pigs fed AP or LP + 2B diets(P < 0.05). The mRNA expression profile of the selected mitochondrial component and mitochondrial biogenesis associated regulators in DSA and ASA also responded differently to dietary BCAA supplementation. These results suggested that the growth performance of growing pigs fed protein restricted diets supplemented with BCAA could catch up to that of the pigs fed AP diets. The results also partly demonstrated that the regulation mechanisms of BCAA are different in the adipose tissues of different depots.

Branched chain amino acids and metabolic regulation

Amino acids are fundamental nutrients required for protein synthesis. The branched chain amino acids (BCAAs) leucine, isoleucine, and valine are the most abundant of the essential amino acids. BCAAs have recently been recognized as having functions in processes other than simple nutrition. For example, metabolic diseases are characterized by higher levels of circulating BCAAs. Moreover, supplementation with or deficiency in BCAAs is closely related to the regulation of metabolic homeostasis. Indeed, leucine deprivation induces increased lipolysis and thermogenesis, which result in fat loss, as well as suppressed lipogenesis and enhanced insulin sensitivity in the liver. Accumulating evidence has indicated that several amino acid sensors, including GCN2, ATF4, mTOR, and AMPK, play pivotal roles in the regulation of lipid metabolism, glucose metabolism, and energy homeostasis. Furthermore, the hypothalamus is critical for sensing amino acid levels and mediates the metabolic adaptation of the body upon limitation of essential amino acids (EAAs) through regulating expression of the S6K1, MC4R, and CRH. In this review, we highlight recent studies investigating the cellular mechanisms linking amino acids, amino acid sensors, metabolic regulation, and metabolic diseases. Amino acid sensing and metabolic regulation have become research hotspots in the metabolic field.