Consumption Of Branched-chain Amino Acids Research Articles

Dietary branched-chain amino acids intake, glycemic markers, metabolic profile, and anthropometric features in a community-based sample of overweight and obese adults

BackgroundExisting research provides conflicting evidence regarding the relationship between estimated branched-chain amino acid (BCAA) intake and metabolic, glycemic markers, and anthropometric characteristics. This research seeks to examine the association between estimated dietary BCAA consumption and glycemic, and metabolic markers, as well as anthropometric parameters in adults classified as overweight or obese.MethodsIn this cross-sectional analysis, we gathered data from 465 overweight and obese individuals aged between 18 and 37 years. To evaluate dietary data, we employed the food frequency questionnaire, and the BCAA content in foods was determined via the United States Department of Agriculture website. We utilized ELISA kits to measure fasting blood glucose (FBS) and lipid profile markers, and additionally calculated low-density lipoprotein (LDL) and insulin sensitivity markers. We assessed sociodemographic status, physical activity (PA), and anthropometric attributes through a method recognized as both valid and reliable. For statistical analysis, we conducted analyses of covariance (ANCOVA), making adjustments for variables including sex, PA, age, energy, and body mass index (BMI).ResultsUpon adjusting for confounders, those in the highest tertiles of BCAA intake exhibited an increase in weight, BMI, waist circumference (WC), waist-to-hip ratio (WHR), and fat-free mass (FFM). Conversely, they demonstrated reduced fat mass (FM) (%) and FM (kg) compared to their counterparts in the lowest tertiles (P < 0.05). Additionally, there was a noted association between greater estimated BCAA intake and reduced LDL levels. Nonetheless, our findings did not reveal a significant relationship between dietary BCAA and glycemic indices.ConclusionsFrom our findings, an increased estimated intake of BCAA seems to correlate with diminished serum LDL concentrations. To gain a more comprehensive understanding of this association, it is imperative that further experimental and longitudinal studies be conducted.

Association between type 2 diabetes and branched chain amino acids (BCAA); a case-control study.

Several amino acids and their derivatives have been implicated in insulin resistance (IR) and Type 2 Diabetes Mellitus (T2DM). This research sought to establish a relationship between the dietary levels of branched-chain amino acids (BCAA) and the risk of T2DM. This case-control study was carried out on 4200 participants consisting of 589 people with T2DM and 3611 non-diabetic aged 35 to 70 years residents in Sabzevar, Iran. Data on the economic-social, employment status, medical history, lifestyle, and sleep habits were collected via interview. The food frequency questionnaire (FFQ) was used to check the nutritional status. Participants' dietary BCAA consumption was estimated using Nutritionist IV software. A significant negative association between the incidence of T2DM and the dietary levels of BCAAs after adjustment for age and sex (OR = 0.972, CI 95%:0.648-0.996, P = 0.022). The negative association remained significant after additional adjustments for body mass index (BMI) and physical activity (OR = 0.967, CI 95%: 0.943-0.992, P = 0.010). Interestingly, a positive association was found between T2DM and total BCAAs (OR = 1.067, CI 95%: 1.017-1.119, P = 0.008), Isoleucine (OR = 1.248, CI 95%: 1.043-1.494, P = 0.016), Leucine (OR = 1.165, CI 95%: 1.046-1.299, P = 0.006) and Valine (OR = 1.274, CI 95%: 1.088-1.492, P = 0.003) after further adjustment for calorie intake. Our results demonstrate branched-chain amino acids (BCAAs) including isoleucine, leucine, and valine are negatively associated with the incidence of type 2 diabetes (T2DM) after adjusting for age and sex, BMI, and physical activity. However, adjusting for calorie intake reversed the association between T2DM and BCAAs. These findings suggest that the association between BCAAs and T2DM may be influenced by calorie intake. Future longitudinal studies are warranted. The online version contains supplementary material available at 10.1007/s40200-023-01247-9.

Dietary consumption of branched-chain amino acids among Chinese middle-aged and elderly population aged 50 and over in 2015

To investigate the dietary consumption of branched-chain amino acids(BCAAs)intake status of middle-aged and elderly people 50 years and older in China, and to analyze the distribution differences between different ages, genders and regions. The research sample was derived from the 2015 Chinese adult chronic disease and nutrition monitoring data. The survey adopts the stratified multi-stage cluster random sampling method, and selects 298 monitoring points from 31 provinces(autonomous regions and municipalities), a total of 44 218 people aged 50 years and over were sampled. Condiment weighing method, 24-hour dietary review method, and weighing method were used to obtain individual dietary data, and the dietary BCAAs intake of middle-aged and elderly people was calculated based on the Chinese Food Composition Table. In 2015, the dietary BCAAs of middle-aged and elderly people in China accounted for 45.1% of leucine, 29.8% of valine and 25.1% of isoleucine. The top six dietary sources were cereals, red meat, vegetables, fish and seafood, beans and eggs. There were differences in the intake of three branched-chain amino acids(F=1926.67, P&lt;0.01), the intake of leucine was greater than that of valine, and the intake of valine was greater than isoleucine. There were statistically significant differences in dietary BCAAs intake between different age groups, genders, urban and rural areas and regions(P&lt;0.01), among which men were greater than women(t=12.89, P&lt;0.01), and the south was greater than the north(t=-6.36, P&lt;0.01), the eastern part was larger than the central part, and the central part was larger than the western part(F=82.42, P&lt;0.01). The intake of BCAAs decreased with the increase of age groups(F=22.69, P&lt;0.01), and there was no significant difference in age groups over 70 years old. The dietary intake of BCAAs was higher in the eastern coastal areas and Inner Mongolia, Xinjiang and Tibet. There were gender, age and geographical differences in dietary BCAAs intake among middle-aged and elderly people in China, and the contribution of various foods to dietary BCAAs was also different.

13C-Metabolic flux analysis of 3T3-L1 adipocytes illuminates its core metabolism under hypoxia

Hypoxia has been identified as a major factor in the pathogenesis of adipose tissue inflammation, which is a hallmark of obesity and obesity-linked type 2 diabetes mellitus. In this study, we have investigated the impact of hypoxia (1% oxygen) on the physiology and metabolism of 3T3-L1 adipocytes, a widely used cell culture model of adipose. Specifically, we applied parallel labeling experiments, isotopomer spectral analysis, and 13C-metabolic flux analysis to quantify the impact of hypoxia on adipogenesis, de novo lipogenesis and metabolic flux reprogramming in adipocytes. We found that 3T3-L1 cells can successfully differentiate into lipid-accumulating adipocytes under hypoxia, although the production of lipids was reduced by about 40%. Quantitative flux analysis demonstrated that short-term (1 day) and long-term (7 days) exposure to hypoxia resulted in similar reprogramming of cellular metabolism. Overall, we found that hypoxia: 1) reduced redox and energy generation by more than 2-fold and altered the patterns of metabolic pathway contributions to production and consumption of energy and redox cofactors; 2) redirected glucose metabolism from pentose phosphate pathway and citric acid cycle to lactate production; 3) rewired glutamine metabolism, from net glutamine production to net glutamine catabolism; 4) suppressed branched chain amino acid consumption; and 5) reduced biosynthesis of odd-chain fatty acids and mono-unsaturated fatty acids, while synthesis of saturated even-chain fatty acids was not affected. Together, these results highlight the profound impact of extracellular microenvironment on adipocyte metabolic activity and function.

Effect of branched-chain amino acids on food intake and indicators of hunger and satiety- a narrative summary

Branched-chain amino acids (BCAA) found in protein are most notably known for their ability to increase protein synthesis, explaining their appeal to athletes seeking muscle hypertrophy, expedited recovery, and preservation of lean body mass. In addition to anabolic benefits, protein consumption has been implicated in the regulation of food intake, which represents an important variable in treating and preventing obesity. Protein-rich foods (such as dairy) have previously been linked to improved satiety and reduced food intake, however, there appear to be discrepancies in the effects of different protein types (for example whey versus casein) on appetite. One potential explanation for these differences is the varied amino acid composition of each protein type. Thus, one theory is that high levels of BCAA may be responsible in-part for the satiating properties of protein. Therefore, the purpose of this narrative review is to describe the effects of BCAA (both individually and in combination) on hormonal regulators of satiety including ghrelin, leptin, peptide tyrosine tyrosine (PYY), cholecystokinin (CCK), and glucagon-like peptide-1 (GLP-1). This report also summarizes the effect of BCAA on food intake and subjective measures of hunger. Several reports suggest BCAA stimulate leptin activity (secretion or sensitivity) and GLP-1 levels and suppress ghrelin levels. Similarly, intake is reduced, and subjective measures of hunger are often lower following consumption of BCAA. However, inconsistencies in experimental protocols and related findings make the true effect of BCAA on satiety and food intake difficult to discern, and therefor worthy of further investigation. • Protein-rich foods have previously been linked with satiety and reduced food intake. • BCAA may be responsible in-part for the satiating properties of protein. • BCAA may reduce food intake and subjective measures of hunger.

Branched-Chain Amino Acids and Mitochondrial Biogenesis: An Overview and Mechanistic Summary.

Branched-chain amino acids (BCAA) are essential in the diet and promote several vital cell responses which may have benefits for health and athletic performance, as well as disease prevention. While BCAA are well-known for their ability to stimulate muscle protein synthesis, their effects on cell energetics are also becoming well-documented, but these receive less attention. In this review, much of the current evidence demonstrating BCAA ability (as individual amino acids or as part of dietary mixtures) to alter regulators of cellular energetics with an emphasis on mitochondrial biogenesis and related signaling is highlighted. Several studies have shown, both in vitro and in vivo, that BCAA (either individual or as a mixture) may promote signaling associated with increased mitochondrial biogenesis including the upregulation of master regulator of mitochondrial biogenesis peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), as well as numerous downstream targets and related function. However, sparse data in humans and the difficulty of controlling variables associated with feeding studies leave the physiological relevance of these findings unclear. Future well-controlled diet studies will be needed to assess if BCAA consumption is associated with increased mitochondrial biogenesis and improved metabolic outcomes in healthy and/or diseased human populations.

Association Between the Risk of Hyperuricemia and Changes in Branched-Chain Amino Acids Intake Over Twelve Years: A Latent Class Trajectory Analysis From the China Health and Nutrition Survey, 1997-2009.

ObjectiveThis study aims to identify dietary branched-chain amino acids (BCAA) consumption trajectories in Chinese adults and to evaluate their association with the risk of hyperuricemia (HU).MethodsCohort data from the China Health and Nutrition Survey 1997–2009 were adopted in this research. A total of 6,810 participants aged ≥18 years were included in this study. Participants were designated into four subgroups on basis of the trajectories of dietary BCAA consumption. Cox proportional hazards models were performed to discuss the relationships between varied trajectories and the risk of HU after adjusting potential confounders. The intermediary effect of differential blood indexes between the trajectories and the risk of HU was explored with mediation analysis.ResultsFour distinct trajectory groups of dietary BCAA consumption were identified. Compared with the low stable trajectory group, high to low trajectory group was greatly related to an increased risk of HU (HR 1.35 (95% CI 1.03 to 1.79)) with modification for covariates. Total cholesterol (TC), hemoglobin A1c (HbA1c), fasting blood glucose (FBG), and triglyceride (TG) partially regulated trajectories and HU.ConclusionGradually decreasing dietary BCAA intake increased the risk of HU, which is, at least, partially mediated by TC, HbA1c, FBG, and TG levels.

The Effect of Branched Chain Amino Acids and Vitamin E on Muscle Damage

Objective The use of amino acid supplements among athletes for reducing muscle injuries has become more popular. This study aims to examine the effect of branched-chain amino acids (BCAA) consumption before exhaustive exercise along with one month vitamin E supplementation on lactate dehydrogenase (LDH) and creatine kinase (CK) levels of active females. Methods In this study, 32 active female students of Razi University in Kermanshah, Iran aged 18-23 years were selected and, after obtaining the informed consent form them, were randomly divided into four groups of placebo (n=8), Vitamin E (n=8), BCAA (n=8), and Vitamin E+BCAA (n=). Vitamin E was consumed as 400 IU daily for a month and BCAA with lemon juice was consumed 2.5 hours before exercise four times with a 30-min interval. The exercise program included 30 minutes of cycling on an ergometer with 50% of the aerobic capacity, and immediately followed by cycling with 75% of the aerobic capacity until the exhaustion. Sampling was done immediately and 48 hours after the exercise, and data were analyzed using Shapiro-Wilk test, repeated measures ANOVA, Bonferroni test, and Pearson correlation test in SPSS software, version 22. Results None of the supplements had a significant effect on levels of LDH and CK immediately after the exercise (P&gt;0.05), but 48 hours after the exercise, the mean levels of LDH and CK decreased in BCAA group (CK: 199.4±11.00, LDH: 213.2±23.44) and Vitamin E+BCAA (CK: 188.3±3.20, LDH: 208.3±40.12) compared to Vitamin E and placebo groups (P = 0.001). Their lowest levels was observed in the Vitamin E+BCAA group which was negatively correlated to plasma leucine and isoleucine levels (P = 0.001). Conclusion Although BCAA consumption alone before exhaustive exercise can reduce muscular damage indicators in active females, it seems that leucine and isoleucine along with Vitamin E supplementation is more effective in reducing muscular damage.

The Dietary Branched-Chain Amino Acids Transition and Risk of Type 2 Diabetes Among Chinese Adults From 1997 to 2015: Based on Seven Cross-Sectional Studies and a Prospective Cohort Study.

BackgroundThe situation is grim for the prevention and control of type 2 diabetes (T2D) and prediabetes in China. Serum and dietary branched-chain amino acids (BCAAs) were risk factors for T2D. However, there is a lack of information on trends in consumption of BCAAs and the risk of T2D associated with BCAAs intake, based on nationally representative data in China. Thus, we aimed to comprehensively describe the dietary BCAAs transition and risk of T2D, at a national level among Chinese adults from 1997 to 2015.MethodsThe data sources were the China Health and Nutrition Survey (CHNS) and China Nutrition and Health Survey (CNHS). Cross-sectional data on intake were obtained from CHNS (1997, n = 9,404), CHNS (2000, n = 10,291), CHNS (2004, n = 9,682), CHNS (2006, n = 9,553), CHNS (2009, n = 9,811), CHNS (2011, n = 12,686) and CNHS (2015, n = 71,695). Prospective cohort data were obtained CHNS (1997–2015, n = 15,508).ResultsFrom 1997 to 2015, there was a significant decreasing trend in the BCAAs intake of Chinese adults in all subgroups (P < 0.0001) except for Leu in 80 or older, and a decreasing trend in the consumption of BCAAs after 40 years old (P < 0.05). The mean intake of BCAAs in the population of cohort study was 11.83 ± 3.77g/day. The 95% CI was above the HR of 1.0, when the consumptions were higher than 14.01, 3.75, 6.07, 4.21 g/day in BCAAs, Ile, Leu and Val, based on RCS curves. According to the Cox proportional hazards models, Compared with individuals with BCAAs consumption of 10.65–12.37 g/day, the multivariable-adjusted HR for diabetes was 2.26 (95% CI 1.45 to 3.51) for individuals with consumption of BCAAs more than 18.52 g/day. A statistically significant positive association between BCAAs intake and risk of T2D was observed in males or participants aged 45 years and older, but not in females or participants younger than 45 years.ConclusionOur results reveal a trend toward decreased BCAAs intake in Chinese from 1997 to 2015. After 40 years of age, consumption of BCAAs declined with increasing age. Higher BCAAs intake was associated with higher risk of T2D. This relationship is more stable among men and middle-aged and elderly people.

Clinical Condition, Nutritional Status and Food Consumption of Patients with Maple Syrup Urine Disease

Maple syrup urine disease (MSUD) is an inborn error of metabolism caused by an enzyme deficiency and leads to the accumulation of branched-chain amino acids (BCAAs), which are toxic to the body in high concentrations. Part of the treatment is based on dietary control and a reduced intake of BCAAs. The objective of this study was to describe the clinical condition, nutritional status and food consumption of patients with MSUD. Two patients diagnosed with MSUD were selected. Interviews and nutritional, body composition, and food consumption assessments were carried out. Energy, macronutrients, micronutrients, BCCAs, and fiber contents were estimate. All clinical data were obtained from medical records. Both patients showed manifestations of neuropsychomotor development delay with intellectual disability. Regarding nutritional status, one patient was overweight, and the other was underweight, with low functional capacity in both of them. A monotonous dietary pattern and a low intake of energy, proteins, vitamins, and minerals were observed, but there was a high consumption of BCAAs by one of the patients. Developmental and intellectual disabilities were observed besides the changes in nutritional status (underweight and overweight), low functional capacity, dietary inadequacies in terms of energy, macronutrients, and micronutrients, besides a monotonous food consumption pattern.

Consumption of a Branched-Chain Amino Acid (BCAA) during Days 2-10 of Pregnancy Causes Abnormal Fetal and Placental Growth: Implications for BCAA Supplementation in Humans.

A relatively large branched-chain amino acid (BCAA) supplement, consumed for more than 10 days, appears to be especially effective at alleviating muscle damage and soreness during intense human training. However, perturbations in amino acid and protein consumption could have unwanted transgenerational effects on male and female reproduction. This paper hypothesizes that isoleucine consumption by female mice from days 2 to 10 of pregnancy will alter fetal and placental growth later in gestation. Mice that had received 118 mM isoleucine in their drinking water delivered pups on day 19 of pregnancy that were 9% larger than normal, whereas the reverse was true for pups born on day 20. Moreover, the inverse correlation between birth weight and litter size was lost in mice that previously consumed excess isoleucine. Similarly, the normal correlations between fetal and placental weights were lost by day 18 of pregnancy in mice that had consumed excess isoleucine. Mice that consumed excess isoleucine had placentas smaller than, and fetuses larger than normal on day 18 of pregnancy, but the reverse was true on day 15. Other unintended and unexpected effects of BCAA consumption should be studied more thoroughly due to the increasing use of BCAAs to alleviate muscle damage and soreness in athletes.

Protein-Related Dietary Parameters and Frailty Status in Older Community-Dwellers across Different Frailty Instruments

The present study investigated the associations between frailty status and (a) daily protein intake, (b) daily body weight-adjusted protein intake, (c) branched-chain amino acid (BCAA) consumption, (d) evenness of protein distribution across main meals, (e) number of daily meals providing at least 30 g of protein, and (f) number of daily meals providing at least 0.4 g protein/kg of body weight in community-dwelling older adults. The relationship between frailty status and protein-related dietary parameters was explored across different frailty assessment tools. Two hundred older adults were enrolled in the study. Participant frailty status was determined according to a modified Fried’s frailty phenotype (mFP), the FRAIL scale, and the Study of Osteoporotic Fracture (SOF) index. Diet was assessed by 24-h dietary recall, while diet composition was estimated using a nutritional software. A frailty instrument-dependent relationship was observed between frailty status and protein-related dietary parameters. Protein consumption was associated with frailty status only in participants identified as frail according to the mFP. In addition, protein and BCAA intake was found to be greater in robust and pre-frail participants relative to their frail counterparts. Our findings suggest that the association between frailty and protein-related dietary parameters is tool dependent. Specifically, protein and BCAA consumption appears to be lower only in older adults identified as frail by the mFP.

PPAR\u03b3/Pgc-1\u03b1-Fndc5 pathway up-regulation in gastrocnemius and heart muscle of exercised, branched chain amino acid diet fed mice

BackgroundPrevious studies have revealed the inductive effect of branched-chain amino acids (BCAAs) catabolism on fatty acid oxidation and metabolism, especially in muscle cells. In the present investigation, we have attempted to address whether a combination of BCAAs supplement consumption with aerobic exercise could elaborate the expression of PPARγ, Pgc-1α and Fndc5 genes in gastrocnemius muscle and heart tissue of male C57BL/6 mice.MethodsThirty-six young male mice with an average weight of 18 ± 2 g were selected. Mice were randomly assigned to 6 groups: 20 mg/mL of BCAAs consumption with simultaneous exercise-training, 60 mg/mL of BCAAs consumption with simultaneous exercise-training, exercise-trained with no BCAAs consumption group, 20 mg/mL BCAAs without exercise-training, 60 mg/mL BCAAs without exercise-training, and untrained mice without BCAAs consumption.ResultsThe findings showed a combination of 20 mg/mL BCAAs with aerobic exercise significantly increased Fndc5, PPARγ, Pgc-1α gene expression in skeletal muscles although, circulating Irisin levels remained unchanged (p < 0.05). Interestingly, plasma urea and lactate levels were significantly increased in 60 mg/mL BCAAs administrated mice which performed exercised (p < 0.05). Two-way analysis of variance (ANOVA) was used to examine significant difference between groups and sedentary group.ConclusionsResults showed inductive effect of 20 mg/mL BCAAs on expression levels of Fndc5, PPARγ, Pgc-1α in gastrocnemius muscle similar with counterparts in heart tissue. Of note, higher serum irisin levels were detected after 20 mg/mL BCAAs supplementation coincided with the exercise.Graphical abstractAn Overview on supplemantaion of branched chain amoinoacids on metablism of skeletal muscle and heart

Abstract 3442: Genome-wide association study reveals potential biomarkers after pulmonary metastasectomy for head and neck cancer

Abstract Introduction: At least 10% of head neck cancer squamous cell carcinoma (HNSCC) progress to pulmonary metastases with overall survival (OS) around 12 months. Whether aggressively pulmonary metastasectomy (PM) improving survival or not is controversial. Method and materials: Different head neck cancer patients receiving PM from thoracic surgeon were enrolled from 2003 to 2012. Matched HNSCC and adenoid cystic carcinoma (ACC) samples as control were selected to perform whole-exon sequencing (WES) and identify potential biomarkers between short- and long- term surviving groups after metastasectomy. Identified mutant genes were mapped into possible signaling pathways by using DAVID ( https://david.ncifcrf.gov/). Result: A total of 31 head and neck cancer patients were enrolled and the survivals were different significantly among cancer types. Eight matched PM samples (3 short-term post-metastaectomy survival (PMS) HNSCC, 3 long-term HNSCC, and 2 ACC), with differently clinical outcomes (PMS, P = 0.016; OS, P = 0.015), were enrolled for WES. Eighteen percentages (18%, 306/1706) of identified genetic alternations were mapped into DAVID. Cancer-associated signal pathways were top-ranked related to short-term HNSCC; hematopoietic cell lineage associated pathways for long-term HNSCC; complement and coagulation cascades associated pathways for ACC. The overlapped genes between short-term HNSCC and ACC were relative to metabolic-associated pathway, such as branched-chain amino acid consumption (P &amp;lt; 0.001, fold enrichment (FE) = 7.97) and the metabolism of arginine and proline metabolism (P &amp;lt; 0.001, FE = 4.96). The overlapped genes between long-term HNSCC and ACC were relative to focal adhesion (P =0.008, FE = 2.84) and ECM-receptor interaction (P = 0.015, FE = 4.08). Conclusion: Genome-wide association study effectively separated clinical outcome of head neck cancer patients and successfully identified specific mutations for prognosis after PM. Basic characteristics of patients receiving whole-exon sequencing for pulmonary metastatic tumor.GroupAgeGenderPrimary tumor siteHistological typeInitial pathologic stagingBrief historyOverall survivalPost-metastasectomy survivalCase 1Short-term survival86.0MaleHypopharynxSquamous cell carcinomapT4aN2bSurgical resection followed by adjuvant radiotherapy; one metastatic nodule at right lower lung was resected.23.914.4Case 2Short-term survival60.9MaleOropharynxSquamous cell carcinomapT4aN1Surgical resection followed by adjuvant chemoradiotherapy; two metastatic nodules at right and left upper lung were resected.26.011.9Case 3Short-term survival47.1MaleOropharynxSquamous cell carcinomapT4aN2bInduction chemotherapy followed by definitive surgical resection and adjuvant chemoradiotherapy; one left upper lung metastasis was resected.22.87.1Case 4Long-term survival38.9MaleHypopharynxSquamous cell carcinomapT2N2bSurgical resection followed by adjuvant radiotherapy; multiple bilateral lung metastases with sequential wedge resection for left and right side lesions52.140.2Case 5Long-term survival51.3MaleHypopharynxSquamous cell carcinomapT3N2bSurgical resection followed by adjuvant chemoradiotherapy; 3 metastatic lesion at right upper, middle and left lower lung were resected.89.842.7Case 6Long-term survival54.4MaleHypopharynxSquamous cell carcinomapT4aN2bSurgical resection followed by adjuvant chemoradiotherapy; 2 metastatic lesions at bilateral lung apices with sequential wedge resection134.891.1Case 7Control39.6FemaleOral cavityAdenoid cystic carcinomapT4aNoSurgical resection followed by adjuvant chemoradiotherapy; 2 metastatic nodules at right upper and middle lung were resected130.187.0Case 8Control46.2FemaleRight maxillary sinus and nasal cavityAdenoid cystic carcinomaUnknownSurgical resection followed by adjuvant radiotherapy; 2 metastatic nodules at right upper and middle lung were resected195.079.9 Citation Format: Hsueh-Ju Lu, Chih-Cheng Hsieh, Chi-Chun Yeh, Yi-Chen Yeh, Muh-Hwa Yang, Chi-Ying F. Huang, Peter Mu-Hsin Chang. Genome-wide association study reveals potential biomarkers after pulmonary metastasectomy for head and neck cancer [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3442.

Dietary intake of branched-chain amino acids in a mouse model of Alzheimer's disease: Effects on survival, behavior, and neuropathology

IntroductionHigh levels of plasmatic branched-chain amino acids (BCAA), commonly used as dietary supplements, are linked to metabolic risk factors for Alzheimer's disease (AD). BCAA directly influence amino acid transport to the brain and, therefore, neurotransmitter levels. We thus investigated the impact of BCAA on AD neuropathology in a mouse model. Methods3xTg-AD mice were fed either a control diet or a high-fat diet from 6 to 18 months of age. For the last 2 months, dietary BCAA content was adjusted to high (+50%), normal (+0%), or low (−50%). ResultsMice fed a BCAA-supplemented high-fat diet displayed higher tau neuropathology and only four out of 13 survived. Mice on the low-BCAA diet showed higher threonine and tryptophan cortical levels while performing better on the novel object recognition task. DiscussionThese preclinical data underscore a potential risk of combining high-fat and high BCAA consumption, and possible benefits from BCAA restriction in AD.

MiR-124-3p affects the formation of intramuscular fat through alterations in branched chain amino acid consumption in sheep

Intramuscular fat is used to determine meat quality in animals; however, factors affecting branched chain amino acid (BCAA) catabolism, which fuels adipogenesis and lipogenesis, remain unclear. To better understand the post-transcriptional influence on BCAA catabolism during adipogenesis, we investigated the role of miR-124-3p. Stromal vascular fraction (SVF) cells were isolated from skeletal muscle of sheep, and induced to differentiate. We determined the roles of miR-124-3p and its predicted target, branched chain keto acid dehydrogenase E1, alpha polypeptide (BCKDHA), in adipogenic differentiation and lipogenesis of SVFs after overexpressing or inhibiting miR-124-3p or BCKDHA, respectively. miR-124-3p altered the luciferase activity of constructs containing 3′-UTR of BCKDHA and the formation of lipid droplets, along with the adipogenic markers and BCAA consumption. Besides, the adipogenic performance and BCAA consumption in BCKDHA-overexpressing or knocked-down SVFs and the expression of adipogenic marker genes were altered. We demonstrate that miR-124-3p is an important factor for adipogenesis and provide insights into the formation of intramuscular fat in animals.

Dietary BCAA Intake Is Associated with Demographic, Socioeconomic and Lifestyle Factors in Residents of São Paulo, Brazil.

Background: Identifying which risk groups have a higher intake of branched chain amino acids (BCAA) is important for the planning of public policies. This study was undertaken to investigate BCAA consumption, the foods contributing to that consumption and their association with demographic, socioeconomic and lifestyle factors. Methods: Data from the Health Survey of São Paulo, a cross-sectional population-based survey (n = 1662; age range 12–97 years), were used. Dietary intake was measured using 24-h dietary recalls. Baseline characteristics were collected. Associations between BCAA intake and demographic, socioeconomic and lifestyle factors were determined using linear regression. Results: Total BCAA intake was 217.14 mg/kg·day (Leu: 97.16 mg/kg·day; Ile: 56.44 mg/kg·day; Val: 63.54 mg/kg·day). BCAA intake was negatively associated with female sex in adolescents and adult groups, with no white race in adolescents, and with former smoker status in adults. Conversely, BCAA was positively associated with household per capita income in adolescents and adults. No associations were observed in the older adults group. Main food contributors to BCAA were unprocessed red meat, unprocessed poultry, bread and toast, beans and rice. Conclusions: Adolescents and adults were the most vulnerable to having their BCCA intake influenced by demographic, socioeconomic and lifestyle factors.

Chronic dietary exposure to branched chain amino acids impairs glucose disposal in vegans but not in omnivores.

Branched chain amino acids (BCAA) are among nutrients strongly linked with insulin sensitivity (IS) measures. We investigated the effects of a chronic increase of BCAA intake on IS in two groups of healthy subjects differing in their basal consumption of BCAA, that is, vegans and omnivores. Eight vegans and eight matched omnivores (five men and three women in each group) received 15 g (women) or 20 g (men) of BCAA daily for 3 months. Anthropometry, blood analyses, glucose clamp, arginine test, subcutaneous abdominal adipose tissue (AT) and skeletal muscle (SM) biopsies (mRNA levels of selected metabolic markers, respiratory chain (RC) activity) were performed at baseline, after the intervention and after a 6 month wash-out period. Compared with omnivores, vegans had higher IS at baseline (GIR, glucose infusion rate: 9.6±2.4 vs 7.1±2.4 mg/kg/min, 95% CI for difference: 0.55 to 5.82) that declined after the intervention and returned to baseline values after the wash-out period (changes in GIR with 95% CI, 3-0 months: -1.64 [-2.5; -0.75] and 9-3 months: 1.65 [0.75; 2.54] mg/kg/min). No such change was observed in omnivores. In omnivores the intervention led to an increased expression of lipogenic genes (DGAT2, FASN, PPARγ, SCD1) in AT. SM RC activity increased in both groups. Negative impact of increased BCAA intake on IS was only detected in vegans, that is, subjects with low basal amino acids/BCAA intake, which appear to be unable to induce sufficient compensatory changes within AT and SM on a BCAA challenge.

Cumulative consumption of branched-chain amino acids and incidence of type 2 diabetes.

Plasma branched-chain amino acids (BCAAs, including leucine, isoleucine and valine) were recently related to risk of type 2 diabetes (T2D). Dietary intake is the only source of BCAAs; however, little is known about whether habitual dietary intake of BCAAs affects risk of T2D. We assessed associations between cumulative consumption of BCAAs and risk of T2D among participants from three prospective cohorts: the Nurses' Health Study (NHS; followed from 1980 to 2012); NHS II (followed from 1991 to 2011); and the Health Professionals Follow-up Study (HPFS; followed from 1986 to 2010). We documented 16097 incident T2D events during up to 32 years of follow-up. After adjustment for demographics and traditional risk factors, higher total BCAA intake was associated with an increased risk of T2D in men and women. In the meta-analysis of all cohorts, comparing participants in the highest quintile with those in the lowest quintile of intake, hazard ratios (95%confidence intervals) were for leucine 1.13 (1.07-1.19), for isoleucine 1.13 (1.07-1.19) and for valine 1.11 (1.05-1.17) (all P for trend < 0.001). In a healthy subsample, higher dietary BCAAs were significantly associated with higher plasma levels of these amino acids (P for trend = 0.01). Our data suggest that high consumption of BCAAs is associated with an increased risk of T2D.

Decreased Consumption of Branched-Chain Amino Acids Improves Metabolic Health.

Protein-restricted (PR), high-carbohydrate diets improve metabolic health in rodents, yet the precise dietary components that are responsible for these effects have not been identified. Furthermore, the applicability of these studies to humans is unclear. Here, we demonstrate in a randomized controlled trial that a moderate PR dietalso improves markers of metabolic health in humans. Intriguingly, we find that feeding mice a diet specifically reduced in branched-chain amino acids (BCAAs) is sufficient to improve glucose tolerance and body composition equivalently to a PR diet via metabolically distinct pathways. Our results highlight a critical role for dietary quality at the level of amino acids in the maintenance of metabolic health and suggest that diets specifically reduced in BCAAs, or pharmacological interventions in this pathway, may offer a translatable way to achieve many of the metabolic benefits of a PR diet.