Branched chain amino acids, as essential amino acids, can be used to synthesize nitrogen-containing compounds and also act as signal molecules to regulate substance metabolism. Studies have shown that the elevated level of branched chain amino acids is closely related to insulin resistance and type 2 diabetes. It can affect insulin signal transduction by activating mammalian target of rapamycin (mTOR) signal pathway, and regulate insulin resistance by damaging lipid metabolism and affecting mitochondrial function. In addition, abnormal catabolism of branched amino acids can lead to the accumulation of metabolic intermediates, such as branched chain α-keto acids, 3-hydroxyisobutyrate and β-aminoisobutyric acid. Branched chain α-keto acids and 3-hydroxyisobutyrate can induce insulin resistance by affecting insulin signaling pathway and damaging lipid metabolism. β-aminoisobutyric acid can improve insulin resistance by reducing lipid accumulation and inflammatory reaction and enhancing fatty acid oxidation. This paper systematically reviewed the regulatory effects and mechanisms of branched chain amino acids and their metabolic intermediates on insulin resistance, which will provide a new direction for the prevention and treatment of insulin resistance and type 2 diabetes.
Humans ; Amino Acids, Branched-Chain/metabolism* ; Insulin Resistance/physiology* ; Diabetes Mellitus, Type 2 ; Insulin/pharmacology* ; Keto Acids/metabolism*

Branched-chain amino acids (BCAAs) are essential amino acids that are not synthesized in our body; thus, they need to be obtained from food. They have shown to provide many physiological and metabolic benefits such as stimulation of pancreatic insulin secretion, milk production, adipogenesis, and enhanced immune function, among others, mainly mediated by mammalian target of rapamycin (mTOR) signaling pathway. After identified as a reliable marker of obesity and type 2 diabetes in recent years, an increasing number of studies have surfaced implicating BCAAs in the pathophysiology of other diseases such as cancers, cardiovascular diseases, and even neurodegenerative disorders like Alzheimer's disease. Here we discuss the most recent progress and review studies highlighting both correlational and potentially causative role of BCAAs in the development of these disorders. Although we are just beginning to understand the intricate relationships between BCAAs and some of the most prevalent chronic diseases, current findings raise a possibility that they are linked by a similar putative mechanism.
Adipogenesis ; Alzheimer Disease ; Amino Acids, Branched-Chain ; Amino Acids, Essential ; Cardiovascular Diseases ; Chronic Disease ; Heart Failure ; Insulin ; Metabolism ; Milk ; Neurodegenerative Diseases ; Obesity ; Sirolimus

OBJECTIVETo evaluate the effect of compound branch chain amino acids injection (Aminic) on protein metabolism in patients with radical resection of cardiac carcinoma.

METHODSEighty patients with radical resection of cardiac carcinoma were randomly divided into two groups:study group (40 cases) with compound branch chain amino acids injection (Aminic), and control group(40 cases) with amino acids(MPR- F). The patients received total parenteral nutrition with equal calorie and nitrogen from 1st-7th days after operation by central or peripheral vein with infusing time over 12 hours per day. The change of body weight was observed. The serum levels of total protein, albumin,pre-albumin,transferring, and fibronectin were measured.

RESULTSThe body weight was decreased in the two groups after operation, while compared with the study group,the body weight was significantly decreased in the control group (P=0.0250). The positive nitrogen balance recovered two days earlier in study group than that in the control group. Decrease of total protein,albumin were more severe in the control group than those in study group (P=0.0446,P=0.0314 respectively). Compared with the control group,the level of Valine was increased (P=0.0073),and the level of Arginine was decreased more obviously in the study group (P= 0.0212).

CONCLUSIONThe compound branch chain amino acids injection (Aminic) is more beneficial for patients with radical resection of cardiac carcinoma to correct negative nitrogen balance,it can also inhibit decomposition of muscles protein,and improve nutritional conditions.

Adult ; Aged ; Aged, 80 and over ; Amino Acids, Branched-Chain ; therapeutic use ; Female ; Heart Neoplasms ; metabolism ; therapy ; Humans ; Male ; Middle Aged ; Parenteral Nutrition ; Postoperative Period ; Prospective Studies ; Proteins ; metabolism

OBJECTIVETo observe the effect of parenteral nutrition (PN) with branched-chain amino acid supplementation on protein metabolism after partial hepatectomy in rats with liver cirrhosis.

METHODSEighteen rats with liver cirrhosis were randomly divided into pre-operation group (n=6), post-operation 8.5% Novamin PN group (n=6) and post-operation 10% Hepa PN group (n=6), with 6 normal rats severing as the normal control group. Five days after the operation, serum albumin (ALB), insulin-like growth factor I (IGF-1) and plasma amino acid spectrum were measured, and ALB mRNA level in the liver was assayed using RT-PCR.

RESULTSPostoperative serum ALB was similar between 10% Hepa PN and 8.5% Novamine PN groups, but the rats in the latter group showed significantly increased serum IGF-1 level, Fischer ratio and hepatic ALB mRNA expression (P<0.05).

CONCLUSIONAdministration of PN with branched-chain amino acid supplementation can ameliorate plasma amino acid spectrum and increase protein synthesis in rats with liver cirrhosis after partial hepatectomy.

Albumins ; metabolism ; Amino Acids, Branched-Chain ; administration & dosage ; therapeutic use ; Animals ; Hepatectomy ; Insulin-Like Growth Factor I ; metabolism ; Liver Cirrhosis ; therapy ; Parenteral Nutrition ; Rats ; Rats, Sprague-Dawley

Maple syrup urine disease(MSUD) is an autosomal recessive disorder involving the metabolism of the branched-chain amino acids(BCAA) such as leucine, isoleucine and valine. The disorder is due to a defect in branched-chain alpha-ketoacid dehydrogenase(BCKAD) and the classic form causes rapid progressive and overwhelming illness beginning in the first weeks of life, present with poor feeding, lethargy, change in muscle tone, acidosis, seizures and coma. The goal of therapy in acutely ill patients with MSUD is an immediate reduction in the plasma levels of the BCAAs and branched-chain ketoacids. In this report, we describe an infant with MSUD who was treated by dietary therapy alone. During the therapy, acrodermatitis enteropathica-like syndrome developed with low plasma isoleucine concentration while she was receiving a formula deficient in BCAAs.
Acer* ; Acidosis ; Acrodermatitis* ; Amino Acids, Branched-Chain ; Coma ; Diet Therapy* ; Diet* ; Humans ; Infant ; Isoleucine ; Lethargy ; Leucine ; Maple Syrup Urine Disease* ; Metabolism ; Plasma ; Seizures ; Valine

OBJECTIVETo observe the change of postoperative fatigue in rats after the effect of branched chain amino acid(BCAA) and associated antagonists on central neurotransmitter 5-HT metabolic pathway, and to investigate the role of 5-HT in the development of postoperative fatigue syndrome(POFS).

METHODSFifty SD rats were randomly divided into sham operation group(C group, n=10), model group(M group, n=10), L-type amino acid transporter inhibitor group(L group, n=10), 5-HT uptake inhibitor group(F group, n=10) and branched chain amino acids(B group, n=10). The rats in the C group and the M group were injected with normal saline, while other three groups were respectively injected with BCH, fluoxetine, BCAA(val:leucine:isoleucine=5:3:2), on preoperative 1 h, postoperative day 1, 2, 3, 4. The rats, except for those in the C group, underwent resection of 70% of the middle small intestine with end-to-end anastomosis. General status of the rats was observed before and after surgery. Morris water maze test, including the hidden platform test and search space test (detecting the learning ability of rats) and tail suspension test (detecting physical endurance of rats) were used to evaluate the degree of POFS from postoperative day 1 to day 7. Concentration of tryptophan(TRP), 5-HT, 5-hydroxyindoleacetic acid (5-HIAA) in different position of brain(hippocampus, striatum, hypothalamus) of rats were measured by high performance liquid chromatography(HPLC) at postoperative day 8.

RESULTSAs compared to the M group, other four groups showed better general condition and less fatigue. In the hidden platform test, M group showed the least time of crossing platform as compared to other four groups(all P<0.05). Meanwhile, M group and B group performed the longer incubation period than C group and L group(all P<0.05). In search space test, M group and B group showed less time of crossing platform, but there were no significant differences among the groups(all P>0.05). In tail suspension test, M group and F group showed lower score of physical strength than L group and B group(all P<0.05). Levels of TRP in the L, F, B groups were lower compared to the M group(all P<0.01) in brain tissue. The least concentration of striatum 5-HT was found in the C group but there were no significant differences among the M, L, F and B groups. Level of 5-HIAA in the M group, only in hypothalamus, was higher than that in the F group(P<0.05), but no significant differences between the M group and the L and B groups were found.

CONCLUSIONBCAA and associated antagonists (BCH, fluoxetine) can improve POFS by reducing the absorption of TRP that results in decreased synthesis of central 5-HT.

Amino Acids, Branched-Chain ; pharmacology ; Animals ; Fatigue ; drug therapy ; Intestine, Small ; surgery ; Postoperative Period ; Rats ; Serotonin ; metabolism ; Serotonin Antagonists ; pharmacology ; Tryptophan

PURPOSE: There have been high rates of false positive and recall in neonatal screening test using the cut-off points set by the manufacturing company. So, it is necessary to re-evaluate the cut-off values to minimize the false positive rates. METHODS: We collected capillary blood in dry filter paper from 996 healthy neonates on the third day in cases of normal vaginal delivery or the fifth day in cases of Cesarean section. The levels of phenylalanine, galactose, 17-hydroxyprogesterone and branched-chain amino acids were measured using enzyme immunoassay. The results were compared with the original cut-off points set by the manufacturing company. RESULTS: The original cut-off points of four substances were 4.0mg/dL, 7.5mg/dL, 35ng/mL, and 8.0mg/dL, respectively, so that false-positive rates were 0.4, 1.6, 3.93, and 0.001%, respectively. When we set the cut-off point at 99.7 percentile using the data from healthy neonates, they should be 4.0mg/dL, 9.2mg/dL, 54.3ng/mL, and 8.0mg/dL, respectively. CONCLUSION: The false-positive and recall rates were higher in galactosemia and congenital adrenal hyperplasia when using the original cut-off points, suggesting that it would be reasonable to modify the cut-off point at 99.7 percentile after measuring those substances from enough of healthy neonates.
17-alpha-Hydroxyprogesterone ; Adrenal Hyperplasia, Congenital ; Amino Acids, Branched-Chain ; Capillaries ; Cesarean Section ; Female ; Galactose ; Galactosemias ; Humans ; Immunoenzyme Techniques ; Infant, Newborn ; Metabolism, Inborn Errors* ; Neonatal Screening* ; Phenylalanine ; Pregnancy

PURPOSE: There have been high rates of false positive and recall in neonatal screening test using the cut-off points set by the manufacturing company. So, it is necessary to re-evaluate the cut-off values to minimize the false positive rates. METHODS: We collected capillary blood in dry filter paper from 996 healthy neonates on the third day in cases of normal vaginal delivery or the fifth day in cases of Cesarean section. The levels of phenylalanine, galactose, 17-hydroxyprogesterone and branched-chain amino acids were measured using enzyme immunoassay. The results were compared with the original cut-off points set by the manufacturing company. RESULTS: The original cut-off points of four substances were 4.0mg/dL, 7.5mg/dL, 35ng/mL, and 8.0mg/dL, respectively, so that false-positive rates were 0.4, 1.6, 3.93, and 0.001%, respectively. When we set the cut-off point at 99.7 percentile using the data from healthy neonates, they should be 4.0mg/dL, 9.2mg/dL, 54.3ng/mL, and 8.0mg/dL, respectively. CONCLUSION: The false-positive and recall rates were higher in galactosemia and congenital adrenal hyperplasia when using the original cut-off points, suggesting that it would be reasonable to modify the cut-off point at 99.7 percentile after measuring those substances from enough of healthy neonates.
17-alpha-Hydroxyprogesterone ; Adrenal Hyperplasia, Congenital ; Amino Acids, Branched-Chain ; Capillaries ; Cesarean Section ; Female ; Galactose ; Galactosemias ; Humans ; Immunoenzyme Techniques ; Infant, Newborn ; Metabolism, Inborn Errors* ; Neonatal Screening* ; Phenylalanine ; Pregnancy

In this study, we evaluated the effect of the herbicide propyl 4-(2-(4,6-dimethoxypyrimidin-2-yloxy)benzylamino) benzoate (ZJ0273) on barley growth and explored the potential to trigger growth recovery through the application of branched-chain amino acids (BCAAs). Barley plants were foliar-sprayed with various concentrations of ZJ0273 (100, 500, or 1000 mg/L) at the four-leaf stage. Increasing either the herbicide concentration or measurement time after herbicide treatment significantly impaired plant morphological parameters such as plant height and biomass, and affected physiological indexes, i.e. maximal photochemical efficiency (F_v/F_m), quantum yield of photosystem II (Ф_PSII), net photosynthetic rate (P_n), and chlorophyll meter value (soil and plant analyzer development (SPAD)). Cellular injury of herbicide-treated plants was also evidenced by increased levels of reactive oxygen species (ROS) and antioxidative enzyme activity. Elevated levels of herbicide significantly reduced the activity of acetolactate synthase (ALS)-a key enzyme in the biosynthesis of BCAAs. In a separate experiment, growth recovery in herbicide-stressed barley plants was studied using various concentrations of BCAAs (10, 50, 100, and 200 mg/L). Increasing BCAA concentration in growth media significantly increased the biomass of herbicide-stressed barley seedlings, but had no significant effect on non-stressed plants. Further, BCAAs (100 mg/L) significantly down-regulated ROS and consequently antioxidant enzyme levels in herbicide-stressed plants. Our results showed that exogenous application of BCAAs could reverse the inhibitory effects of ZJ0273 by restoring protein biosynthesis in barley seedlings.
Amino Acids, Branched-Chain/administration & dosage* ; Antioxidants/metabolism* ; Benzoates/pharmacology* ; Biomass ; Chlorophyll/metabolism* ; Herbicides/pharmacology* ; Hordeum/metabolism* ; Photosynthesis/drug effects* ; Plant Leaves/metabolism* ; Reactive Oxygen Species/metabolism* ; Seedlings/metabolism*

OBJECTIVETo investigate the effect of respiratory syncytial virus (RSV)-related pulmonary infection on endogenous metabolites in large intestinal mucosa in BALB/c mice using metabolomics technology based on gas chromatography-mass spectrometry (GC-MS).

METHODSMice were randomly divided into a control group and a RSV pneumonia model group (n=16 each). The mouse model of RSV pneumonia was established using intranasal RSV infection (100×TCID, 50 μL/mouse, once a day). After 7 days of intranasal RSV infection, the mice were sacrificed and GC-MS was used to identify endogenous metabolites and measure the changes in their relative content in colon tissue. SMCA-P12.0 software was used to perform principal component analysis (PCA) and orthogonal partial least squares-discriminant analysis (OPLS-DA) for endogenous metabolites in colon tissue. The differentially expressed metabolites in colon tissue were imported into the metabolic pathway platform Metaboanalyst to analyze related metabolic pathways.

RESULTSPCA and OPLS-DA showed significant differences between the control and RSV pneumonia model groups. A total of 32 metabolites were identified in the colon tissue of the mice with RSV pneumonia. The RSV pneumonia model group had significant increases in the content of leucine, isoleucine, glycine, alanine, arachidonic acid, and lactic acid, which were related to the valine, leucine, isoleucine, arachidonic acid, and pyruvic acid metabolic pathways.

CONCLUSIONSRSV pneumonia might cause metabolic disorders in the large intestinal tissue in mice.

Amino Acids, Branched-Chain ; metabolism ; Animals ; Female ; Gas Chromatography-Mass Spectrometry ; Intestinal Mucosa ; metabolism ; Intestine, Large ; metabolism ; pathology ; Lung ; pathology ; Mice ; Mice, Inbred BALB C ; Pneumonia, Viral ; metabolism ; Respiratory Syncytial Virus Infections ; metabolism