Abomasal infusion of branched-chain amino acids or branched-chain keto-acids alter lactation performance and liver triglycerides in fresh cows

Background Dairy cows are at high risk of fatty liver disease in early lactation,but current preventative measures are not always effective.Cows with fatty liver have lower circulating branched-chain amino acid(BCAA)concentra-tions whereas cows with high circulating BCAA levels have low liver triglyceride(TG).Our objective was to determine the impact of BCAA and their corresponding ketoacids(branched-chain ketoacids,BCKA)on production performance and liver TG accumulation in Holstein cows in the first 3 weeks postpartum.Methods Thirty-six multiparous Holstein cows were used in a randomized block design experiment.Cows were abomasally infused for the first 21 d postpartum with solutions of 1)saline(CON,n=12);2)BCA(67 g valine,50 g leu-cine,and 34 g isoleucine,n=12);and 3)BCK(77 g 2-ketovaline calcium salt,57 g 2-ketoleucine calcium salt,and 39 g 2-ketoisoleucine calcium salt,n=12).All cows received the same diet.Treatment effects were determined using PROC GLIMMIX in SAS.Results No differences were detected for body weight,body condition score,or dry matter intake averaged over the first 21 d postpartum.Cows receiving BCK had significantly lower liver TG concentrations compared to CON(6.60%vs.4.77%,standard error of the mean(SEM)0.49)during the first 3 weeks of lactation.Infusion of BCA increased milk yield(39.5 vs.35.3 kg/d,SEM 1.8),milk fat yield(2.10 vs.1.69 kg/d,SEM 0.08),and lactose yield(2.11 vs.1.67 kg/d,SEM 0.07)compared with CON.Compared to CON,cows receiving BCA had lower plasma glucose(55.0 vs.59.2 mg/dL,SEM 0.86)but higherβ-hydroxybutyrate(9.17 vs.6.00 mg/dL,SEM 0.80).Conclusions Overall,BCAA supplementation in this study improved milk production,whereas BCKA supplementa-tion reduced TG accumulation in the liver of fresh cows.

Decoding the nexus:branched-chain amino acids and their connection with sleep,circadian rhythms,and cardiometabolic health

The sleep-wake cycle stands as an integrative process essential for sustaining optimal brain function and,either directly or indirectly,overall body health,encompassing metabolic and cardiovascular well-being.Given the heightened metabolic activity of the brain,there exists a considerable demand for nutrients in comparison to other organs.Among these,the branched-chain amino acids,comprising leucine,isoleucine,and valine,display distinctive significance,from their contribution to protein structure to their involvement in overall metabolism,especially in cerebral processes.Among the first amino acids that are released into circulation post-food intake,branched-chain amino acids assume a pivotal role in the regulation of protein synthesis,modulating insulin secretion and the amino acid sensing pathway of target of rapamycin.Branched-chain amino acids are key players in influencing the brain's uptake of monoamine precursors,competing for a shared transporter.Beyond their involvement in protein synthesis,these amino acids contribute to the metabolic cycles ofγ-aminobutyric acid and glutamate,as well as energy metabolism.Notably,they impact GABAergic neurons and the excitation/inhibition balance.The rhythmicity of branchedchain amino acids in plasma concentrations,observed over a 24-hour cycle and conserved in rodent models,is under circadian clock control.The mechanisms underlying those rhythms and the physiological consequences of their disruption are not fully understood.Disturbed sleep,obesity,diabetes,and cardiovascular diseases can elevate branched-chain amino acid concentrations or modify their oscillatory dynamics.The mechanisms driving these effects are currently the focal point of ongoing research efforts,since normalizing branched-chain amino acid levels has the ability to alleviate the severity of these pathologies.In this context,the Drosophila model,though underutilized,holds promise in shedding new light on these mechanisms.Initial findings indicate its potential to introduce novel concepts,particularly in elucidating the intricate connections between the circadian clock,sleep/wake,and metabolism.Consequently,the use and transport of branched-chain amino acids emerge as critical components and orchestrators in the web of interactions across multiple organs throughout the sleep/wake cycle.They could represent one of the so far elusive mechanisms connecting sleep patterns to metabolic and cardiovascular health,paving the way for potential therapeutic interventions.

Heterogeneously elevated branched-chain/aromatic amino acids among new-onset type-2 diabetes mellitus patients are potentially skewed diabetes predictors

BACKGROUND The lack of specific predictors for type-2 diabetes mellitus(T2DM)severely impacts early intervention/prevention efforts.Elevated branched-chain amino acids(BCAAs:Isoleucine,leucine,valine)and aromatic amino acids(AAAs:Tyrosine,tryptophan,phenylalanine)show high sensitivity and specificity in predicting diabetes in animals and predict T2DM 10-19 years before T2DM onset in clinical studies.However,improvement is needed to support its clinical utility.AIM To evaluate the effects of body mass index(BMI)and sex on BCAAs/AAAs in new-onset T2DM individuals with varying body weight.METHODS Ninety-seven new-onset T2DM patients(<12 mo)differing in BMI[normal weight(NW),n=33,BMI=22.23±1.60;overweight,n=42,BMI=25.9±1.07;obesity(OB),n=22,BMI=31.23±2.31]from the First People’s Hospital of Yunnan Province,Kunming,China,were studied.One-way and 2-way ANOVAs were conducted to determine the effects of BMI and sex on BCAAs/AAAs.RESULTS Fasting serum AAAs,BCAAs,glutamate,and alanine were greater and high-density lipoprotein(HDL)was lower(P<0.05,each)in OB-T2DM patients than in NW-T2DM patients,especially in male OB-T2DM patients.Arginine,histidine,leucine,methionine,and lysine were greater in male patients than in female patients.Moreover,histidine,alanine,glutamate,lysine,valine,methionine,leucine,isoleucine,tyrosine,phenylalanine,and tryptophan were significantly correlated with abdominal adiposity,body weight and BMI,whereas isoleucine,leucine and phenylalanine were negatively correlated with HDL.CONCLUSION Heterogeneously elevated amino acids,especially BCAAs/AAAs,across new-onset T2DM patients in differing BMI categories revealed a potentially skewed prediction of T2DM development.The higher BCAA/AAA levels in obese T2DM patients would support T2DM prediction in obese individuals,whereas the lower levels of BCAAs/AAAs in NW-T2DM individuals may underestimate T2DM risk in NW individuals.This potentially skewed T2DM prediction should be considered when BCAAs/AAAs are to be used as the T2DM predictor.

Susceptibility of dairy cows to subacute ruminal acidosis is reflected in both prepartum and postpartum bacteria as well as odd-and branched-chain fatty acids in feces

Background:The transition period is a challenging period for high-producing dairy cattle.Cows in early lactation are considered as a group at risk of subacute ruminal acidosis(SARA).Variability in SARA susceptibility in early lactation is hypothesized to be reflected in fecal characteristics such as fecal pH,dry matter content,volatile and odd-and branched-chain fatty acids(VFA and OBCFA,respectively),as well as fecal microbiota.This was investigated with 38 periparturient dairy cows,which were classified into four groups differing in median and mean time of reticular pH below 6 as well as area under the curve of pH below 6.Furthermore,we investigated whether fecal differences were already obvious during a period prior to the SARA risk(prepartum).Results:Variation in reticular pH during a 3-week postpartum period was not associated with differences in fecal pH and VFA concentration.In the postpartum period,the copy number of fecal bacteria and methanogens of unsusceptible(UN)cows was higher than moderately susceptible(MS)or susceptible(SU)cows,while the genera Ruminococcus and Prevotellacea_UCG-001 were proportionally less abundant in UN compared with SU cows.Nevertheless,only a minor reduction was observed in iso-BCFA proportions in fecal fatty acids of SU cows,particularly iso-C15:0and iso-C16:0,compared with UN cows.Consistent with the bacterial changes postpartum,the lower abundance of Ruminococcus was already observed in the prepartum fecal bacterial communities of UN cows,whereas Lachnospiraceae_UCG-001 was increased.Nevertheless,no differences were observed in the prepartum fecal VFA or OBCFA profiles among the groups.Prepartum fecal bacterial communities of cows were clustered into two distinct clusters with 70%of the SU cows belonging to cluster 1,in which they represented 60%of the animals.Conclusions:Inter-animal variation in postpartum SARA susceptibility was reflected in post-and prepartum fecal bacterial communities.Differences in prepartum fecal bacterial communities could alert for susceptibility to develop SARA postpartum.Our results generated knowledge on the association between fecal bacteria and SARA development which could be further explored in a prevention strategy.

Is branched-chain amino acid nutritional supplementation beneficial or detrimental in heart failure?

Sarcopenia or cachexia is often complicated in heart failure.Nutritional support,particularly branched-chain amino acid(BCAA)supplementation,is a candidate treatment for improving sarcopenia or cachexia in elderly patients.However,the efficacy of BCAA supplementation in patients with heart failure has not been established,and the issue is comparatively more complex.Indeed,there are conflicting reports on the efficacy of BCAA supplementation.The evidence for including BCAA supplementation in treating patients with heart failure was reviewed,and the complexity of the issue was discussed.

Role of the metabolism of branched-chain amino acids in the development of Alzheimer’s disease and other metabolic disorders

Alzheimer’s disease is an incurable chronic neurodegenerative disorder and the leading cause of dementia,imposing a growing economic burden upon society.The disease progression is associated with gradual deposition of amyloid plaques and the formation of neurofibrillary tangles within the brain parenchyma,yet severe dementia is the culminating phase of the enduring pathology.Converging evidence suggests that Alzheimer’s disease-related cognitive decline is the outcome of an extremely complex and persistent pathophysiological process.The disease is characterized by distinctive abnormalities apparent at systemic,histological,macromolecular,and biochemical levels.Moreover,besides the well-defined and self-evident characteristic profuse neurofibrillary tangles,dystrophic neurites,and amyloid-beta deposits,the Alzheimer’s disease-associated pathology includes neuroinflammation,substantial neuronal loss,apoptosis,extensive DNA damage,considerable mitochondrial malfunction,compromised energy metabolism,and chronic oxidative stress.Likewise,distinctive metabolic dysfunction has been named a leading cause and a hallmark of Alzheimer’s disease that is apparent decades prior to disease manifestation.State-of-theart metabolomics studies demonstrate that altered branched-chain amino acids(BCAAs)metabolism accompanies Alzheimer’s disease development.Lower plasma valine levels are correlated with accelerated cognitive decline,and,conversely,an increase in valine concentration is associated with reduced risk of Alzheimer’s disease.Additionally,a clear BCAAs-related metabolic signature has been identified in subjects with obesity,diabetes,and atherosclerosis.Also,arginine metabolism is dramatically altered in Alzheimer’s disease human brains and animal models.Accordingly,a potential role of the urea cycle in the Alzheimer’s disease development has been hypothesized,and preclinical studies utilizing intervention in the urea cycle and/or BCAAs metabolism have demonstrated clinical potential.Continual failures to offer a competent treatment strategy directed against amyloid-beta or Tau proteins-related lesions,which could face all challenges of the multifaceted Alzheimer’s disease pathology,led to the hypothesis that hyperphosphorylated Tau and deposited amyloid-beta proteins are just hallmarks or epiphenomena,but not the ultimate causes of Alzheimer’s disease.Therefore,approaches targeting amyloid-beta or Tau are not adequate to cure the disease.Accordingly,the modern scientific vision of Alzheimer’s disease etiology and pathogenesis must reach beyond the hallmarks,and look for alternative strategies and areas of research.

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 by3-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.

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).METHODS:We investigated the usefulness of preintervention with BCAAs by comparing patients treated with BCAAs at 12.45 g/d orally for at least 2 wk before TACE or RFA and those not receiving such pretreatment.A total of 270 patients with hepatocellular carcinoma complicated by cirrhosis were included in the study.Mean changes from baseline(Δ)in serum albumin(Alb),C-reactive protein(CRP),and transaminase levels,as well as peak body temperature were also determined and compared at days 2,5,and 10 after the start of TACE or RFA.RESULTS:In patients who underwent TACE or RFA,BCAA pre-intervention significantly suppressed the development of post-intervention hypoalbuminemia and reduced inflammatory reactions during the subsequent clinical course.After TACE,theΔAlb peaked on day 2,remained constantly lower in BCAA-treated patients,compared to the control group,and was-0.13±0.42g/dL in BCAA-treated patients and-0.33±0.51 g/dL in untreated patients on day 10.TheΔCRP was also significantly lower in BCAA-treated patients on days2,5 and 10 after TACE.Like the trends noted after TACE,a similar tendency was noted as to theΔAlb andΔCRP after RFA.The changes in serum Alb level were inversely correlated with CRP changes;therefore,a possible involvement of the anti-inflammatory effect of BCAAs was inferred as a factor contributory to the suppression of decrease in serum Alb level.CONCLUSION:Pre-intervention with BCAAs may hasten the recovery of serum Alb level and mitigate postoperative complications in patients undergoing TACE or RFA.

Branched-chain amino acids supplementation has beneficial effects on the progression of liver cirrhosis:A meta-analysis

BACKGROUND Liver cirrhosis(LC)is currently the 11^(th) most common cause of death and 15^(th) cause of morbidity globally.The treatment of LC is mainly aimed at etiological intervention,lifestyle intervention,prevention and treatment of complications and nutritional treatment.Nutritional treatment of LC mainly includes increasing dietary intake,food intake time and branched-chain amino acids(BCAAs).Despite the recommendation of BCAAs in some guidelines,adverse effects have been reported in studies so the efficacy and safety of BCAAs remain controversial.Currently,BCAAs have been widely used in chronic liver disease,while the summary of the effect of BCAAs on long-term prognosis is rare.AIM To determine the effects of BCAAs in patients with LC.METHODS The PubMed,Cochrane Library,Embase and Web of Science databases were searched.The retrieval deadline was 1 October 2021 and there were no language restrictions set in the retrieval.The study was performed in strict accordance with the inclusion and exclusion criteria.Nine studies were finally included.The primary outcome was complications of LC.The secondary outcomes were nutritional status and liver function.This meta-analysis used the Review Manager,version 5 statistical package(Cochrane Collaboration,Oxford,England)for analysis.RESULTS The analysis included nine studies that consisted of 1080 patients(554 in the BCAA groups and526 in the control groups).The nine studies were randomized control trials(RCTs).The quality of the studies was assessed using the risk of bias method recommended by the Cochrane Collaboration.BCAAs reduced the rate of complications in LC patients[Risk ratio:0.70,95%confidence interval(CI):0.56-0.88,P=0.002]and improved patients’albumin levels[std mean difference SMD:0.26,95%CI:0.12-0.40,P=0.0002].Meanwhile,BCAAs significantly ameliorated the levels of alanine transaminase(SMD:-2.03,95%CI:-2.52 to-1.53,P<0.00001)and aspartate aminotransferase(SMD:-1.8,95%CI:-2.14 to-1.46,P<0.00001).Meanwhile,glucose in the LC was significantly increased in BCAA-treated patients(MD:13.04,95%CI:6.81-19.89,P=0.0002).CONCLUSION BCAAs reduce the incidence of complications in patients with LC and ameliorate nutritional status.

Effects of Branched-chain Amino Acids on Nutritional Metabolism and Pharmacoeconomics in Patients with Severe Abdominal Trauma

Objective:To observe the influences of branched-chain amino acids(BCAAs)on nutrition metabolism and prognosis of patients with severe abdominal trauma;at the same time,to analyze and evaluate the pharmacoeconomics of it.Methods:A total of 75 severe abdominal trauma patients were recruited from June 2016 to December 2017 and randomly divided into control group and observation group.After surgery and basic treatment,parenteral nutrition support therapy with iso-nitrogen and iso-calorie of both groups was administered.Meanwhile,an equivalent of 8.5%(18AA-Ⅱ)and 10%(20AA)compound AA injection was administrated to the control and observation groups,respectively.The nitrogen balance,serum protein level and plasma amino spectrum of the patients were observed before and after treatment.Besides,the hospital stay,survival rate,complications,adverse reactions and hospitalization costs were also compared.Results:After a 7-day course treatment,the nitrogen balance level of the two groups was significantly improved,but no significant difference was found between them.In addition,the serum protein level and plasma amino spectrum of the two groups was generally improved when compared to before treatment.Compared with the control group,the level of albumin and transferrin in the observation group was improved significantly after treatment,while no difference in plasma amino spectrum was found between the two groups.Moreover,the cost analysis showed remarkably reduced hospitalization costs in the observation group.Conclusion:To a certain degree,BCAAs could improve the nutritional metabolism and prognosis of patients with severe abdominal trauma,and have good cost-effectiveness.

Dietary branched-chain amino acids modulate the dynamics of calcium absorption and reabsorption in proteinrestricted pigs

Background:Very low-protein(VLP)diets negatively impact calcium(Ca)metabolism and absorption.The objective of this study was to investigate the effect of supplemental branched-chain amino acids(BCAA)and limiting amino acids(LAA)on Ca digestibility,absorption and reabsorption in pigs fed with VLP diets.Forty-eight piglets were assigned to six treatments:positive control(PC),negative control(NC),and NC containing LAA 25%,LAA 50%,LAA+BCAA 25%(LB25)and LAA+BCAA 50%(LB50)more than recommendations.Results:Relative to PC or NC,LB25 and LB50 had higher digestibility of Ca and plasma Ca and phosphorus(P),but lower plasma vitamin D3.LB50 tended to increase vitamin D receptor transcript and protein in the gut,but decreased mRNA or protein abundance of parathyroid hormone 1 receptor(PTH1R),calbindin 1(CALB1),cytochrome P450 family 27 subfamily B member 1 and occludin in small intestine.LB50 increased the transcript of cytochrome P450 family 24 subfamily A member 1 and PTH1R but decreased the transcript of transient receptor potential cation channel subfamily V member 5,CALB1 and solute carrier family 17 member 4 in kidney.Conclusion:Overall,BCAA increased Ca digestibility through regulating the transcellular and paracellular Ca absorption in the gut and reabsorption in kidney during protein restriction.

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.

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.

Branched-chain/aromatic amino acids as integrated biomarker of type 2 diabetes mellitus: a systematic review and meta-analysis

Background:As type 2 diabetes mellitus(T2DM)biomarkers,branched-chain amino acids(BCAAs:valine,leucine and isoleucine)and aromatic amino acids(AAAs:phenylalanine,tryptophan and tyrosine)may be correlated with the occurrence and development of T2DM.However,there is still no consensus on the disperse and isolated biomarkers of T2DM.Purpose:To explore the correlation between amino acids and T2DM based on integrated biomarker approach revealed.Methods:PubMed,Web of Science and CNKI were selected to search the literature published until August 31,2019.The included studies described the association between BCAAs,AAAs and T2DM.Random effect model and fixed effect model were adopted in pooled analysis to determine mean difference and 95 percent confidence interval of metabolites.Integrated biomarker was constructed in form of concentration change ratios or risk ratio(RR),relative risk(HR)and odds ratio(OR)of BCAAs and AAAs to reflect the integrated change information of amino acids.Results:The selected 20 studies contained 14942 healthy individuals and 3615 T2DM patients.The levels of BCAAs,phenylalanine and tyrosine both in plasma and serum samples were increased among all T2DM patients compared with those of the healthy control subjects(P<0.00001).However,the mean difference of tryptophan concentration was not statistically significant(P=0.60).The concentration change ratios or HR/RR/OR of BCAAs and AAAs were connected to form integrated biomarker.Conclusion:The integrated biomarker including BCAAs and AAAs could reflect the basic characteristics of T2DM,which has the potential clinical value on comprehensive diagnosis of T2DM.

Effects of L-carnitine and Branched-Chain Amino Acids on Energy Metabolism,Body Composition,and Delayed-Onset Muscle Soreness after Exercise in Healthy Subjects

Background Specific nutrients combined with exercise may prevent a loss of lean body mass and consequently prevent sarcopenia.We examined the effects of 2 weeks of supplementation with L-carnitine and a single dose of branched-chain amino acids(BCAAs)on energy metabolism and body composition before and after exercise and on post-exercise muscle soreness in healthy subjects.Methods A total of 12 young,untrained,healthy women were randomly assigned to two groups who received either 2 weeks of supplementation with L-carnitine(1000 mg/day)and a single dose of BCAAs plus 200 kcal energy(LCAR+BCAA group,n=6)or 200 kcal energy alone(control group,n=6)before 60 min of exercise.Energy substrate metabolism and body composition by bio-impedance were examined before and after exercise.Delayed-onset muscle soreness(DOMS)was evaluated by using a visual analogue scale for 3 days after exercise.Results Serum concentrations of free and acyl-L-carnitine in the LCAR+BCAA group were not significantly different from those in the control group.There were no significant differences in body composition before or after exercise between the two groups.Although serum free fatty acid levels 120 min after the oral ingestion of BCAAs were significantly lower in the LCAR+BCAA group than in the control group,there were no significant differences in serum free fatty acid levels immediately after and 60 min after exercise.DOMS for 3 days after exercise was lower in the LCAR+BCAA group than in the control group,but this difference was not significant.Conclusion Continuous supplementation with L-carnitine combined with a dose of BCAAs in young,untrained,healthy subjects caused a blunted response of stimulated lipolysis after exercise.

The effect of lengths of branched-chain fatty alcohols on the efficacy and safety of docetaxel-prodrug nanoassemblies

The self-assembly prodrugs are usually consisted of drug modules,activation modules,and assembly modules.Keeping the balance between efficacy and safety by selecting suitable modules remains a challenge for developing prodrug nanoassemblies.This study designed four docetaxel(DTX)prodrugs using disulfide bonds as activation modules and different lengths of branched-chain fatty alcohols as assembly modules(C_(16),C_(18),C_(20),and C_(24)).The lengths of the assembly modules determined the self-assembly ability of prodrugs and affected the activation modules’sensitivity.The extension of the carbon chains improved the prodrugs’self-assembly ability and pharmacokinetic behavior while reducing the cytotoxicity and increased cumulative toxicity.The use of C_(20) can balance efficacy and safety.These results provide a great reference for the rational design of prodrug nanoassemblies.

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 regulate plant growth by affecting the homeostasis of mineral elements in rice

Dear Editor,Branched-chain amino acids(BCAAs)are essential amino acids that must be obtained from the diet for humans and animals.Branched-chain amino acid transaminases(BCATs)catalyze a key step in the BCAA synthesis pathway,however,little is known about their biological roles in planta.In this study,we functionally characterized two BCATs,OsBCAT4 and OsBCAT5,in rice and showed that they regulate the development of rice roots by affecting the levels of mineral elements.

Insulin resistance and the metabolism of branched-chain amino acids

Insulin resistance(IR)is a key pathological feature of metabolic syndrome and subsequently causes serious health problems with an increased risk of several common metabolic disorders.IR related metabolic disturbance is not restricted to carbohydrates but impacts global metabolic network.Branched-chain amino acids(BCAAs),namely valine,leucine and isoleucine,are among the nine essential amino acids,accounting for 35%of the essential amino acids in muscle proteins and 40%of the preformed amino acids required by mammals.The BCAAs are particularly responsive to the inhibitory insulin action on amino acid release by skeletal muscle and their metabolism is profoundly altered in insulin resistant conditions and/or insulin deficiency.Although increased circulating BCAA concentration in insulin resistant conditions has been noted for many years and BCAAs have been reported to be involved in the regulation of glucose homeostasis and body weight,it is only recently that BCAAs are found to be closely associated with IR.This review will focus on the recent findings on BCAAs from both epidemic and mechanistic studies.

Branched-chain amino acids partially recover the reduced growth of pigs fed with protein-restricted diets through both central and peripheral factors

The objective of this study was to assess the growth efficiency of pigs fed with protein-restricted diets supplemented with branched-chain amino acids(BCAA)and limiting amino acids(LAA)above the rec-ommended levels.Following 2 weeks of adaptation,48 young barrows were weight matched and randomly assigned to 6 treatments(8 pigs/treatment)for 4 weeks:positive control(PC)with standard protein,negative control(NC)with very low protein containing LAA(i.e.,Lys,Met,Thr and Trp)at rec-ommended levels,and NC containing LAA 25%(L25),LAA 50%(L50),LAA+BCAA(i.e.,Leu,Ile and Val)25%(LB25)and LAA+BCAA 50%(LB50)more than recommendations.Feed intake(FI)and body weight(BW)were measured daily and weekly,respectively.At week 6,blood samples were collected,all pigs euthanized and tissue samples collected.The data were analyzed by univariate GLM or mixed procedure(SPSS)and the means were separated using paired Student's t-test followed by Benjamini-Hochberg correction.Relative to PC,NC had decreased FI,BW,unsupplemented plasma essential amino acids,serum insulin-like growth factor-I(IGF-I)and hypothalamic neuropeptide Y(NPY)(P<0.01).Compared to NC,L25 or L50,LB50 had increased BW and serum IGF-I and decreased plasma serotonin and both LB25 and LB50 had higher FI,plasma BCAA,hypothalamic 5-hydroxytryptamine-receptor 2A and NPY and jejunal 5-hydroxytryptamine-receptor 7(P<0.01).Overall,supplementation of protein-restricted diets with increased levels of dietary BCAA partially recovered the negative effects of these diets on growth through improved IGF-I concentration and FI,which was associated with changed expression of serotonin receptors,blood AA and hypothalamic NPY.