Amino Acid Sensor Research Articles

The Arabidopsis Target of Rapamycin kinase regulates ammonium assimilation and glutamine metabolism.

In eukaryotes, a target of rapamycin (TOR) is a well-conserved kinase that controls cell metabolism and growth in response to nutrients and environmental factors. Nitrogen (N) is an essential element for plants, and TOR functions as a crucial N and amino acid sensor in animals and yeast. However, knowledge of the connections between TOR and the overall N metabolism and assimilation in plants is still limited. In this study, we investigated the regulation of TOR in Arabidopsis (Arabidopsis thaliana) by the N source as well as the impact of TOR deficiency on N metabolism. Inhibition of TOR globally decreased ammonium uptake while triggering a massive accumulation of amino acids, such as Gln, but also of polyamines. Consistently, TOR complex mutants were hypersensitive to Gln. We also showed that the glutamine synthetase inhibitor glufosinate abolishes Gln accumulation resulting from TOR inhibition and improves the growth of TOR complex mutants. These results suggest that a high level of Gln contributes to the reduction in plant growth resulting from TOR inhibition. Glutamine synthetase activity was reduced by TOR inhibition while the enzyme amount increased. In conclusion, our findings show that the TOR pathway is intimately connected to N metabolism and that a decrease in TOR activity results in glutamine synthetase-dependent Gln and amino acid accumulation.

The ENA1 Na+-ATPase Gene Is Regulated by the SPS Sensing Pathway and the Stp1/Stp2 Transcription Factors.

The Saccharomyces cerevisiae ENA1 gene, encoding a Na+-ATPase, responds transcriptionally to the alkalinization of the medium by means of a network of signals that involves the Rim101, the Snf1 and PKA kinases, and the calcineurin/Crz1 pathways. We show here that the ENA1 promoter also contains a consensus sequence, located at nt -553/-544, for the Stp1/2 transcription factors, the downstream components of the amino acid sensing SPS pathway. Mutation of this sequence or deletion of either STP1 or STP2 decreases the activity of a reporter containing this region in response to alkalinization as well as to changes in the amino acid composition in the medium. Expression driven from the entire ENA1 promoter was affected with similar potency by the deletion of PTR3, SSY5, or simultaneous deletion of STP1 and STP2 when cells were exposed to alkaline pH or moderate salt stress. However, it was not altered by the deletion of SSY1, encoding the amino acid sensor. In fact, functional mapping of the ENA1 promoter reveals a region spanning from nt -742 to -577 that enhances transcription, specifically in the absence of Ssy1. We also found that the basal and alkaline pH-induced expression from the HXT2, TRX2, and, particularly, SIT1 promoters was notably decreased in an stp1 stp2 deletion mutant, whereas the PHO84 and PHO89 gene reporters were unaffected. Our findings add a further layer of complexity to the regulation of ENA1 and suggest that the SPS pathway might participate in the regulation of a subset of alkali-inducible genes.

High dose isoleucine stabilizes nuclear PTEN to suppress the proliferation of lung cancer

PurposeCancer cells require a supply of amino acids, particularly essential amino acids such as branched-chain amino acids (BCAAs, i.e., valine, leucine, and isoleucine), to meet the increased nutrient demands of malignant tumors. The cell-autonomous and non-autonomous roles of altered BCAA supply have been implicated in cancer progression. The critical proteins involved in BCAA uptake, transport, metabolism, etc. serve as potential therapeutic biomarkers in human cancers. Here, we summarize the potential anti-tumor mechanism of BCAA by exploring the chain reaction triggered by increased BCAA supply in the tumor.MethodA system-wide strategy was employed to provide a generic solution to establish the links between BCAA and cancer based on comprehensive omics, molecular experimentation, and data analysis.ResultsBCAA over-supplementation (900 mg/kg) significantly inhibited tumor growth and reduced tumor burden, with isoleucine having the most pronounced effect. Surprisingly, isoleucine inhibited tumor growth independently of mTORC1 activation, a classical amino acid sensor. Exploratory transcriptome analysis revealed that Phosphatase and tensin homolog (PTEN) is the critical factor in the anti-tumor effect of isoleucine. By inhibiting PTEN ubiquitination, isoleucine can promote PTEN nuclear import and maintain PTEN nuclear stability. Interestingly, this process was regulated by isoleucine-tRNA ligase, cytoplasmic (IARS), a direct target of isoleucine. We demonstrated the enhanced interaction between IARS and PTEN in the presence of excess isoleucine. At the same time, IARS knockout leads to loss of isoleucine tumor suppressor ability.ConclusionOverall, our results provide insights into the regulation of the IARS-PTEN anti-tumor axis by isoleucine and reveal a unique therapeutic approach based on enhancing cellular isoleucine supply.

Leucine deprivation results in antidepressant effects via GCN2 in AgRP neurons

Abstract Essential amino acids (EAAs) are crucial nutrients, whose levels change in rodents and patients with depression. However, how the levels of a single EAA affects depressive behaviors remains elusive. Here, we demonstrate that although deprivation of the EAA leucine has no effect in unstressed mice, it remarkably reverses the depression-like behaviors induced by chronic restraint stress (CRS). This beneficial effect is independent of feeding and is applicable to the dietary deficiency of other EAAs. Furthermore, the effect of leucine deprivation is suppressed by central injection of leucine or mimicked by central injection of leucinol. Moreover, hypothalamic agouti-related peptide (AgRP) neural activity changes during CRS and leucine deprivation, and chemogenetically inhibiting AgRP neurons eliminates the antidepressant effects of leucine deprivation. Finally, the leucine deprivation-regulated behavioral effects are mediated by amino acid sensor general control non-derepressible 2 (GCN2) in AgRP neurons. Taken together, our results suggest a new drug target and/or dietary intervention for the reduction of depressive symptoms.

Charge-Selective Aggregation Behavior of Thermoresponsive Polyelectrolytes Having Low Charge Density in Aqueous Solutions of Organic Counterions

The aggregation behavior of thermoresponsive polyelectrolytes with low charge density in aqueous solutions of organic counterions was investigated. We synthesized two thermoresponsive polyelectrolytes: anionic poly(N-isopropylacrylamide-co-(3-sulfopropyl)acrylamide potassium) (P-NIP-SPAK) and cationic poly(N-isopropylacrylamide-co-(3-acrylamidepropyl)trimethylammonium chloride) (P-NIP-AAPTAC). The polyelectrolytes remained soluble in their aqueous solutions even above the lower critical soluble temperature of P-NIP owing to the strong hydration property of the ionic groups. The aggregation occurred when organic counterions were added to the solution. In these solution systems, the concentration of counterions exceeds those of ionic groups introduced into the polyelectrolytes. The aggregation behavior is attributed to the salting-out effect of counterions accommodated near the polyelectrolyte surface by electrostatic interaction. This aggregation behavior was utilized for the charge-selective recognition of amino acids. P-NIP-SPAK aggregated only when basic amino acids were added under acidic conditions, whereas P-NIP-AAPTAC aggregated only when acidic amino acids were added under basic conditions. The results herein demonstrate that P-NIP-SPAK and P-NIP-AAPTAC have the potential to be used as charge-selective polymer sensors for amino acids without having to strictly control the experimental conditions.

Amino acid profiles, amino acid sensors and transporters expression and intestinal microbiota are differentially altered in goats infected with Haemonchus contortus.

Infection with the nematode Haemonchus contortus causes host malnutrition and gastrointestinal injuries. The objective of this study was to investigate the effects of H. contortus infection on gastrointestinal contents of free amino acids (AA), the expression of AA transporters and microbiota with a focus on amino acid metabolism. Twenty-four Xiangdong black goats (13 ± 1.5kg, 6months old) were randomly assigned into the control group (n = 8) and the infected group (n = 16). The results showed that H. contortus infection increased (P < 0.05) the free AA contents in jejunum and ileum digesta. The concentrations of blood threonine, phenylalanine and tyrosine were lower (P < 0.05) in theinfected group as compared to the controlgroup. In the jejunum and ileum epithelium, H. contortus infection significantly (P < 0.05) down-regulated the expression of AA transporter b0,+AT/rBAT and B0AT1, but up-regulated (P < 0.05) the expression of transporter CAT2 and xCT. Furthermore, microbiota in both jejunum (Bifidobacteriaceae, Lachnospiraceae, Bacteroidaceae, Enterobacteriaceae, and Micrococcaceae) and ileum (Acidaminococcaceae, Desulfovibrionaceae, Bacteroidaceae, and Peptostreptococcaceae) were also altered at the family level by H. contortus infection. The commensal bacteriaof jejunum showed a close correlation with amino acids, AA transporters, and amino acid metabolism, especially cystine. In conclusion, H. contortus infection affected theintestinal AA contents and the expression of intestinal AA transporters, suggesting altered AA metabolism and absorption, which were accompanied by changes inthe relative abundances of gut bacteria that mediate amino acid metabolism.

Hyperaminoacidemia induces pancreatic α cell proliferation via synergism between the mTORC1 and CaSR-Gq signaling pathways

Glucagon has emerged as a key regulator of extracellular amino acid (AA) homeostasis. Insufficient glucagon signaling results in hyperaminoacidemia, which drives adaptive proliferation of glucagon-producing α cells. Aside from mammalian target of rapamycin complex 1 (mTORC1), the role of other AA sensors in α cell proliferation has not been described. Here, using both genders of mouse islets and glucagon receptor (gcgr)-deficient zebrafish (Danio rerio), we show α cell proliferation requires activation of the extracellular signal-regulated protein kinase (ERK1/2) by the AA-sensitive calcium sensing receptor (CaSR). Inactivation of CaSR dampened α cell proliferation, which was rescued by re-expression of CaSR or activation of Gq, but not Gi, signaling in α cells. CaSR was also unexpectedly necessary for mTORC1 activation in α cells. Furthermore, coactivation of Gq and mTORC1 induced α cell proliferation independent of hyperaminoacidemia. These results reveal another AA-sensitive mediator and identify pathways necessary and sufficient for hyperaminoacidemia-induced α cell proliferation.

A new mononuclear Fe(iii) Mannich-base complex with selective histidine binding and catechol oxidase activity

The design of amino acid sensors have significant applications in biomarkers.

Effects of the SLC38A2-mTOR Pathway Involved in Regulating the Different Compositions of Dietary Essential Amino Acids-Lysine and Methionine on Growth and Muscle Quality in Rabbits.

In recent years, ensuring food security has been an important challenge for the world. It is important to make good use of China’s domestic local feed resources to provide safe, stable, efficient, and high-quality rabbit meat products for China and the world. Lysine and methionine are the two most limiting essential amino acids in the rabbit diet. However, little is known about the rational composition of lysine and methionine in rabbit diets and the mechanisms that affect growth and development. Accordingly, in this study, we sought to address this knowledge gap by examining the effects of different compositions of lysine and methionine in rabbit diets. Subsequently, the growth status, nitrogen metabolism, blood biochemical indexes, muscle development, muscle quality, and the growth of satellite cells were evaluated in the animals. The results showed that diets containing 0.80% Lys and 0.40% Met improved average daily weight gain, feed conversion, nitrogen use efficiency, and muscle quality in the rabbits (p < 0.05). Additionally, it altered the amino acid transport potential in muscle by upregulating the expression of the SLC7A10 gene (p < 0.05). Meanwhile, the cell viability and the rate of division and migration of SCs in the 0.80% Lys/0.40 % Met composition group were increased (p < 0.05). SLC38A2 and P−mTOR protein expression was upregulated in the 0.80% lysine/0.40% methionine composition group (p < 0.05). In conclusion, 0.80% Lys/0.40% Met was the most suitable lysine and methionine composition in all tested diets. SLC38A2 acted as an amino acid sensor upstream of mTOR and was involved in the 0.80% Lys/0.40% Met regulation of muscle growth and development, thus implicating the mTOR signaling pathway in these processes.

The antitumor activity of a novel GCN2 inhibitor in head and neck squamous cell carcinoma cell lines

BackgroundGeneral control nonderepressible 2 (GCN2) senses amino acid deprivation and activates activating transcription factor 4 (ATF4), which regulates many adaptive genes. We evaluated the impact of AST-0513, a novel GCN2 inhibitor, on the GCN2-ATF4 pathway. Additionally, we evaluated the antitumor effects of AST-0513 in amino acid deprivation in head and neck squamous cell carcinoma (HNSCC) cell lines. MethodsGCN2 expression in HNSCC patient tissues was measured by immunohistochemistry. Five HNSCC cell lines (SNU-1041, SNU-1066, SNU-1076, Detroit-562, FaDu) grown under amino acid deprivation conditions, were treated with AST-0513. After AST-0513 treatment, cell proliferation was measured by CCK-8 assay. Flow cytometry was used to evaluate apoptosis and cell cycle phase. In addition, immunoblotting was performed to evaluate the effect of AST-0513 on the GCN2-ATF4 pathway, cell cycle arrest, and apoptosis. ResultsWe demonstrated that GCN2 was highly expressed in HNSCC patient tissues. AST-0513 inhibited the GCN2-ATF4 pathway in all five HNSCC cell lines. Inhibiting the GCN2-ATF4 pathway during amino acid deprivation reduced HNSCC cell proliferation and prevented adaptation to nutrient stress. Moreover, AST-0513 treatment led to p21 and Cyclin B1 accumulation and G2/M phase cycle arrest. Also, apoptosis was increased, consistent with increased bax expression, increased bcl-xL phosphorylation, and decreased bcl-2 expression. ConclusionA novel GCN2 inhibitor, AST-0513, inhibited the GCN2-ATF4 pathway and has antitumor activity that inhibits proliferation and promotes cell cycle arrest and apoptosis. Considering the high expression of GCN2 in HNSCC patients, these results suggest the potential role of GCN2 inhibitor for the treatment of HNSCC.

Cystine Induced-mTORC2 Activation through Promoting Sin1 Phosphorylation to Suppress Cancer Cell Ferroptosis.

Mechanistic target of rapamycin (mTOR) serves as a central signaling node in the coordination of cell growth and metabolism, and it functions via two distinct complexes, namely, mTOR complex 1 (mTORC1) and mTORC2. mTORC1 plays a crucial role in sensing amino acids, whereas mTORC2 involves in sensing growth factors. However, it remains largely unclear whether mTORC2 can sense amino acids and the mechanism by which amino acids regulate mTORC2 has not been studied. After treating cells with indicated concentration of amino acidsfor different time, it is found that the mTORC2 activation is significantly increased in response to amino acids stimulation, especially cystine. Particularly, knockdown solute carrier family 7 member 11 (SLC7A11)by siRNA shows that SLC7A11-mediated cystine uptake is responsible for activating mTORC2. Mechanistically, the study finds that p38 is activated in response to cystine stimulation, and co-immunoprecipitation (Co-IP) experiments suggest that p38 regulates the assembly of components within mTORC2 by mediating the phosphorylation of the mTORC2 subunit mitogen-activated protein kinase-interacting protein 1 (Sin1) in a cystine-dependent manner. Finally, combined with inducers and inhibitors of ferroptosis and cell viability assay, the study observes that cystine-mediated regulation of the p38-Sin1-mTOR-AKT pathway induces resistance to ferroptosis. These results indicate that cystine-induced activation of the p38-Sin1-mTORC2-AKT pathway suppresses ferroptosis.

MODELLING AND NUMERICAL ANALYSIS OF A HIGHLY-EFFICIENT PCF-BASED AMINO ACID SENSOR

Amino acids not only play a vital role as protein-building constituents in living beings but also have a wide range of applications that include commercial industries such as food additives and flavor enhancers as well as medical sectors to resist numerous disease levels and to treat digestive abscesses, liver ailments, etc. Hence a precise and feasible detection of amino acids is a fervent desire for their appropriate applications. This paper presents an amino acid sensor employing a mono-circular hollow-core PCF. This PCF-based sensor has been designed maintaining high fabrication feasibility. Then the performance of this sensor has been numerically studied engaging finite element method while sensing five types of amino acids. Performance metric exhibits that this sensor has a very low effective material and confinement loss of about 0.003795 cm-1 and 3.065×10-15 cm-1 correspondingly at 2.7 THz for Tryptophan. Besides this sensor has offered approximately 97.12% relative sensitivity maintaining a higher numerical aperture for the same type of amino acid. This sensor has maintained admirable values for all the performance indices for all the five types of amino acids analyzed in this paper. Furthermore, the elementary design of this sensor has opened the door of viable fabrication with the aid of existing sol-gel technique or extrusion with 3D printing method.

Nitrogenated Holey Graphene (C2N-h2D): An excellent sensor for neurotransmitter amino acids

Interactions of amino acids with organic surfaces are highly relevant to the development of modern synthetic biomaterials with biocompatibility and low biotoxicity. Biomolecule-surface interactions vary differently according to the molecule orientation, charge state, and distance from the surface. Furthermore, the electron transfer through molecule/surface could also play a key role in biological recognition and signaling systems. Here, using density functional theory (DFT), we investigated the interactions of three neurotransmitter amino acids (NAAs), namely, glycine (Gly), γ-aminobutyric acid (Gaba), and glutamate (Glu), onto a nanosheet of holey nitrogenated graphene (C2N-h2D). In general, the interactions between amino acids and carbon-based surfaces are mediated through weak van der Waals interactions. However, based on interaction energy and charge density difference calculations, there is a strong physisorption process between NAAs and the C2N structure. In particular, Gaba and Glu can act as exclusive electron donor and acceptor, respectively. Our calculations also reveal that, by changing the orientations from neutral to zwitterionic, the Gly molecule changes from a donor to a strong acceptor of electrons. In the case of electron donation, the resistivity on the C2N surface should be reduced. These findings indicate that the C2N surface is an excellent candidate for high-performance biosensor applications. From the band structure point of view, the NAAs molecules introduce occupied flat bands within the bandgap of the C2N single layer, while the surface energy levels keep the bulk characteristics of the semiconductor system. Finally, the optical absorption spectrum of NAAs-C2N systems reveals that these NAAs seem to improve the photoactivity performance of the C2N structure, with the appearance of intraband transitions.

Role of mTORC1 and GCN2 signaling in immune cells

<p indent="0mm">The amino acid sensing system senses amino acid levels both inside and outside the cell and regulates influences protein synthesis and degradation, but also the differentiation and function of the immune cells. The mammalian target of rapamycin (mTOR) and general control nonderepressible 2 (GCN2) are crucial components of amino acid sensing system. In the present study, we briefly show the progression of mTORC1 and GCN2 in amino acid sensing, and then highlight the importance of mTORC1 and GCN2 in immune cell differentiation and function, and their possible roles in immune-related diseases.

Untargeted Metabolomics Reveals the Function of GPRC6A in Amino Acid and Lipid Metabolism in Mice.

GPRC6A is an amino acid sensor in the cytomembrane. Despite substantial evidence for the role of GPRC6A in metabolism, the specific effects and mechanism by which this gene acts on metabolic processes are still unresolved. In this study, serum biochemical parameters related to liver and kidney function and serum amino acid levels were determined in GPRC6A wild-type (WT) and knockout (KO) mice. An untargeted serum metabolomics analysis was also conducted for the first time, to the best of our knowledge, to decipher the function of GPRC6A in metabolic processes. GPRC6A was involved in lipid and amino acid metabolism, mainly by affecting liver function. A loss of GPRC6A function may perturb bile acid metabolism, thus leading to abnormal unsaturated fatty acid metabolism. GPRC6A KO may lead to excessive protein breakdown under starvation, and the loss of GPRC6A had a significant effect on phenylalanine metabolism-related pathways. Our metabolomics data provide a novel basis for further functional studies of GPRC6A.

An electrochemical chiral sensor for amino acids based on cyclodextrin modified thiophene-based copolymer

Two series of thiophene-based copolymers with cyclodextrins (CDs) grafted on side chain (OH-β-CD-P3HT and Ph-β-CD-P3HT) were synthesized via click reaction, in which the pendant CDs and the polythiophenes (PTs) main chain afford stereo-selective interactions and high conductivity respectively. The copolymers have been employed to construct an electrochemical sensor to achieve efficient enantio-recognition for amino acids. The OH-β-CD-P3HT and Ph-β-CD-P3HT shows reverse interaction preference for D- and L-isomer due to the different interaction mode of native and substituted CDs with chiral guest. It is found that, higher content of block with CD in the copolymer favors lower LOD because of the specific inclusion abilities of CD, while lower content of block with CD is beneficial to chiral selectivity related to the higher structural flexibility of the polymer. The electrochemical sensor was also proven to be capable of determining the relative content of L- or D-isomer in an enantiomer pair.

The amino acid sensor GCN2 controls red blood cell clearance and iron metabolism through regulation of liver macrophages

GCN2 (general control nonderepressible 2) is a serine/threonine-protein kinase that controls messenger RNA translation in response to amino acid availability and ribosome stalling. Here, we show that GCN2 controls erythrocyte clearance and iron recycling during stress. Our data highlight the importance of liver macrophages as the primary cell type mediating these effects. During different stress conditions, such as hemolysis, amino acid deficiency or hypoxia, GCN2 knockout (GCN2-/-) mice displayed resistance to anemia compared with wild-type (GCN2+/+) mice. GCN2-/- liver macrophages exhibited defective erythrophagocytosis and lysosome maturation. Molecular analysis of GCN2-/- cells demonstrated that the ATF4-NRF2 pathway is a critical downstream mediator of GCN2 in regulating red blood cell clearance and iron recycling.

Direct control of lysosomal catabolic activity by mTORC1 through regulation of V-ATPase assembly

Mammalian cells can acquire exogenous amino acids through endocytosis and lysosomal catabolism of extracellular proteins. In amino acid-replete environments, nutritional utilization of extracellular proteins is suppressed by the amino acid sensor mechanistic target of rapamycin complex 1 (mTORC1) through an unknown process. Here, we show that mTORC1 blocks lysosomal degradation of extracellular proteins by suppressing V-ATPase-mediated acidification of lysosomes. When mTORC1 is active, peripheral V-ATPase V1 domains reside in the cytosol where they are stabilized by association with the chaperonin TRiC. Consequently, most lysosomes display low catabolic activity. When mTORC1 activity declines, V-ATPase V1 domains move to membrane-integral V-ATPase Vo domains at lysosomes to assemble active proton pumps. The resulting drop in luminal pH increases protease activity and degradation of protein contents throughout the lysosomal population. These results uncover a principle by which cells rapidly respond to changes in their nutrient environment by mobilizing the latent catabolic capacity of lysosomes.

Genetic and Pharmacological Inhibition of GCN2 Ameliorates Hyperglycemia and Insulin Resistance in Type 2 Diabetic Mice.

It is well recognized that there is a strong and complex association between nonalcoholic fatty liver disease (NAFLD) and type 2 diabetes (T2D). We previously demonstrated that genetic knockout or pharmacological inhibition of general control nondepressible kinase 2 (GCN2), a well-known amino acid sensor, alleviated hepatic steatosis and insulin resistance in obese mice. However, whether GCN2 affects the development of T2D remains unclear. After a high-fat diet (HFD) plus low-dose streptozotocin (STZ) treatments, Gcn2−/− mice developed less hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress than wild-type (WT) mice. Inhibition of GCN2 by intraperitoneal injection of 3 mg/kg GCN2iB (a specific inhibitor of GCN2) every other day for 6 weeks also ameliorated hyperglycemia, insulin resistance, hepatic steatosis, and oxidative stress in HFD/STZ- and leptin receptor deletion (db/db)-induced T2D mice. Moreover, depletion of hepatic GCN2 in db/db mice by tail vein injection of an AAV8-shGcn2 vector resulted in similar improvement in those metabolic disorders. The protective mechanism of GCN2 inhibition in T2D mice was associated with regulation of the glucose metabolic pathway, repression of lipogenesis genes, and activation of the Nrf2 pathway. Together, our data provide evidence that strategies to inhibit hepatic GCN2 activity may be novel approaches for T2D therapy.

Ablation of Tas1r1 Reduces Lipid Accumulation Through Reducing the de Novo Lipid Synthesis and Improving Lipid Catabolism in Mice.

Amino acid sensing plays an important role in regulating lipid metabolism by sensing amino acid nutrient disturbance. T1R1 (umami taste receptor, type 1, member 1) is a membrane G protein-coupled receptor that senses amino acids. Tas1r1-knockout (KO) mice were used to explore the function of umami receptors in lipid metabolism. Compared with wild-type (WT) mice, Tas1r1-KO mice showed decreased fat mass (P < 0.05) and adipocyte size, lower liver triglyceride (7.835 ± 0.809 vs 12.463 ± 0.916 mg/g WT, P = 0.013) and total cholesterol levels (0.542 ± 0.109 vs 1.472 ± 0.044 mmol/g WT, P < 0.001), and reduced lipogenesis gene expressions in adipose and liver tissues. Targeted liver amino acid metabolomics showed that the amino acid content of Tas1r1-KO mice was significantly decreased, which was consistent with the branched-chain ketoacid dehydrogenase protein levels. Proteomics analysis showed that the upregulated proteins were enriched in lipid and steroid metabolism pathways, and parallel reaction monitoring results illustrated that Tas1r1 ablation promoted lipid catabolism through oxysterol 7 α-hydroxylase and insulin-like growth factor binding protein 2. In summary, Tas1r1 disruption in mice could reduce lipid accumulation by reducing de novo lipid synthesis and improving lipid catabolism.