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      Novel metabolic and physiological functions of branched chain amino acids: a review

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          Abstract

          It is widely known that branched chain amino acids (BCAA) are not only elementary components for building muscle tissue but also participate in increasing protein synthesis in animals and humans. BCAA (isoleucine, leucine and valine) regulate many key signaling pathways, the most classic of which is the activation of the mTOR signaling pathway. This signaling pathway connects many diverse physiological and metabolic roles. Recent years have witnessed many striking developments in determining the novel functions of BCAA including: (1) Insufficient or excessive levels of BCAA in the diet enhances lipolysis. (2) BCAA, especially isoleucine, play a major role in enhancing glucose consumption and utilization by up-regulating intestinal and muscular glucose transporters. (3) Supplementation of leucine in the diet enhances meat quality in finishing pigs. (4) BCAA are beneficial for mammary health, milk quality and embryo growth. (5) BCAA enhance intestinal development, intestinal amino acid transportation and mucin production. (6) BCAA participate in up-regulating innate and adaptive immune responses. In addition, abnormally elevated BCAA levels in the blood (decreased BCAA catabolism) are a good biomarker for the early detection of obesity, diabetes and other metabolic diseases. This review will provide some insights into these novel metabolic and physiological functions of BCAA.

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          Obesity-related elevations in plasma leucine are associated with alterations in enzymes involved in branched-chain amino acid metabolism.

          Elevations in branched-chain amino acids (BCAAs) in human obesity were first reported in the 1960s. Such reports are of interest because of the emerging role of BCAAs as potential regulators of satiety, leptin, glucose, cell signaling, adiposity, and body weight (mTOR and PKC). To explore loss of catabolic capacity as a potential contributor to the obesity-related rises in BCAAs, we assessed the first two enzymatic steps, catalyzed by mitochondrial branched chain amino acid aminotransferase (BCATm) or the branched chain alpha-keto acid dehydrogenase (BCKD E1alpha subunit) complex, in two rodent models of obesity (ob/ob mice and Zucker rats) and after surgical weight loss intervention in humans. Obese rodents exhibited hyperaminoacidemia including BCAAs. Whereas no obesity-related changes were observed in rodent skeletal muscle BCATm, pS293, or total BCKD E1alpha or BCKD kinase, in liver BCKD E1alpha was either unaltered or diminished by obesity, and pS293 (associated with the inactive state of BCKD) increased, along with BCKD kinase. In epididymal fat, obesity-related declines were observed in BCATm and BCKD E1alpha. Plasma BCAAs were diminished by an overnight fast coinciding with dissipation of the changes in adipose tissue but not in liver. BCAAs also were reduced by surgical weight loss intervention (Roux-en-Y gastric bypass) in human subjects studied longitudinally. These changes coincided with increased BCATm and BCKD E1alpha in omental and subcutaneous fat. Our results are consistent with the idea that tissue-specific alterations in BCAA metabolism, in liver and adipose tissue but not in muscle, may contribute to the rise in plasma BCAAs in obesity.
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            Functional amino acids in nutrition and health.

            Guoyao Wu (2013)
            The recent years have witnessed growing interest in biochemistry, physiology and nutrition of amino acids (AA) in growth, health and disease of humans and other animals. This results from the discoveries of AA in cell signaling involving protein kinases, G protein-coupled receptors, and gaseous molecules (i.e., NO, CO and H2S). In addition, nutritional studies have shown that dietary supplementation with several AA (e.g., arginine, glutamine, glutamate, leucine, and proline) modulates gene expression, enhances growth of the small intestine and skeletal muscle, or reduces excessive body fat. These seminal findings led to the new concept of functional AA, which are defined as those AA that participate in and regulate key metabolic pathways to improve health, survival, growth, development, lactation, and reproduction of the organisms. Functional AA hold great promise in prevention and treatment of metabolic diseases (e.g., obesity, diabetes, and cardiovascular disorders), intrauterine growth restriction, infertility, intestinal and neurological dysfunction, and infectious disease (including viral infections).
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              A reduced ratio of dietary carbohydrate to protein improves body composition and blood lipid profiles during weight loss in adult women.

              Claims about the merits or risks of carbohydrate (CHO) vs. protein for weight loss diets are extensive, yet the ideal ratio of dietary carbohydrate to protein for adult health and weight management remains unknown. This study examined the efficacy of two weight loss diets with modified CHO/protein ratios to change body composition and blood lipids in adult women. Women (n = 24; 45 to 56 y old) with body mass indices >26 kg/m(2) were assigned to either a CHO Group consuming a diet with a CHO/protein ratio of 3.5 (68 g protein/d) or a Protein Group with a ratio of 1.4 (125 g protein/d). Diets were isoenergetic, providing 7100 kJ/d, and similar amounts of fat ( approximately 50 g/d). After consuming the diets for 10 wk, the CHO Group lost 6.96 +/- 1.36 kg body weight and the Protein Group lost 7.53 +/- 1.44 kg. Weight loss in the Protein Group was partitioned to a significantly higher loss of fat/lean (6.3 +/- 1.2 g/g) compared with the CHO Group (3.8 +/- 0.9). Both groups had significant reductions in serum cholesterol ( approximately 10%), whereas the Protein Group also had significant reductions in triacylglycerols (TAG) (21%) and the ratio of TAG/HDL cholesterol (23%). Women in the CHO Group had higher insulin responses to meals and postprandial hypoglycemia, whereas women in the Protein Group reported greater satiety. This study demonstrates that increasing the proportion of protein to carbohydrate in the diet of adult women has positive effects on body composition, blood lipids, glucose homeostasis and satiety during weight loss.
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                Author and article information

                Contributors
                zhangshihai@scau.edu.cn
                + 86-10-62733588 , zengxf@cau.edu.cn
                656279527@qq.com
                284940931@qq.com
                qiaoshy@nferc.org
                Journal
                J Anim Sci Biotechnol
                J Anim Sci Biotechnol
                Journal of Animal Science and Biotechnology
                BioMed Central (London )
                1674-9782
                2049-1891
                23 January 2017
                23 January 2017
                2017
                : 8
                : 10
                Affiliations
                [1 ]ISNI 0000 0004 0530 8290, GRID grid.22935.3f, State Key Laboratory of Animal Nutrition, College of Animal Science and Technology, , China Agricultural University, ; No.2 Yuanmingyuan West Road, Haidian District, Beijing, 100193 People’s Republic of China
                [2 ]ISNI 0000 0000 9546 5767, GRID grid.20561.30, College of Animal Science, , South China Agricultural University, ; Wushan Avenue, Tianhe District, Guangzhou, 510642 People’s Republic of China
                [3 ]GRID grid.443368.e, College of Animal Science, , Anhui Science & Technology University, ; No. 9 Donghua Road, Fengyang, 233100 Anhui Province People’s Republic of China
                [4 ]Animal Nutrition Institute, Key Laboratory of Animal Disease-ResistanceNutrition,Ministry of Education, Sichuan AgriculturalUniversity, Ya’an, Sichuan China
                Article
                139
                10.1186/s40104-016-0139-z
                5260006
                28127425
                d4277397-4434-4f36-a210-4646d40df6a1
                © The Author(s). 2017

                Open AccessThis article is distributed under the terms of the Creative Commons Attribution 4.0 International License ( http://creativecommons.org/licenses/by/4.0/), which permits unrestricted use, distribution, and reproduction in any medium, provided you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The Creative Commons Public Domain Dedication waiver ( http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated.

                History
                : 26 July 2016
                : 27 December 2016
                Funding
                Funded by: National Key Basic Research Program
                Award ID: 2012CB124704
                Award Recipient :
                Categories
                Review
                Custom metadata
                © The Author(s) 2017

                Animal science & Zoology
                amino acid transporters,glucose transporters,gut health,immunity,lipolysis,mammary health,meat quality,milk production

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