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      Effects of Dietary Chlorogenic Acid Supplementation Derived from Lonicera macranthoides Hand-Mazz on Growth Performance, Free Amino Acid Profile, and Muscle Protein Synthesis in a Finishing Pig Model

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          Abstract

          Chlorogenic acid (CGA), as one of the richest polyphenol compounds in nature, has broad applications in many fields due to its various biological properties. However, initial data on the effects of dietary CGA on protein synthesis and related basal metabolic activity has rarely been reported. The current study is aimed at (1) determining whether dietary CGA supplementation improves the growth performance and carcass traits, (2) assessing whether dietary CGA alters the free amino acid profile, and (3) verifying whether dietary CGA promotes muscle protein synthesis in finishing pigs. Thirty-two (Large × White × Landrace) finishing barrows with an average initial body weight of 71.89 ± 0.92 kg were randomly allotted to 4 groups and fed diets supplemented with 0, 0.02%, 0.04%, and 0.08% CGA, respectively. The results indicated that, compared with the control group, dietary supplementation with 0.04% CGA slightly stimulated the growth performance of pigs, whereas no significant correlation was noted between the dietary CGA levels and animal growth ( P > 0.05). Furthermore, the carcass traits of pigs were improved by 0.04% dietary CGA ( P < 0.01). In addition, dietary CGA significantly improved the serum free amino acid profiles of pigs ( P < 0.01), while 0.04% dietary CGA promoted more amino acids to translocate to skeletal muscles ( P < 0.05). The relative mRNA expression levels of SNAT2 in both longissimus dorsi (LD) and biceps femoris (BF) muscles were augmented in the 0.02% and 0.04% groups ( P < 0.05), and the LAT1 mRNA expression in the BF muscle was elevated in the 0.02% group ( P < 0.05). We also found that dietary CGA supplementation at the levels of 0.04% or 0.08% promoted the expression of p-Akt and activated the mTOR-S6K1-4EBP1 axis in the LD muscle ( P < 0.05). Besides, the MAFbx mRNA abundance in the 0.02% and 0.04% groups was significantly lower ( P < 0.05). Our results revealed that dietary supplementation with CGA of 0.04% improved the free amino acid profile and enhanced muscle protein biosynthesis in the LD muscle in finishing pigs.

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          Bidirectional transport of amino acids regulates mTOR and autophagy.

          Amino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.
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            Chlorogenic acid (CGA): A pharmacological review and call for further research.

            Phenolic acids have recently gained substantial attention due to their various practical, biological and pharmacological effects. Chlorogenic Acid (CGA, 3-CQA) is a most abundant isomer among caffeoylquinic acid isomers (3-, 4-, and 5-CQA), that currently known as 5-CQA as per guidelines of IUPAC. It is one of the most available acids among phenolic acid compounds which can be naturally found in green coffee extracts and tea. CGA is an important and biologically active dietary polyphenol, playing several important and therapeutic roles such as antioxidant activity, antibacterial, hepatoprotective, cardioprotective, anti-inflammatory, antipyretic, neuroprotective, anti-obesity, antiviral, anti-microbial, anti-hypertension, free radicals scavenger and a central nervous system (CNS) stimulator. In addition, it has been found that CGA could modulate lipid metabolism and glucose in both genetically and healthy metabolic related disorders. It is speculated that CGA can perform crucial roles in lipid and glucose metabolism regulation and thus help to treat many disorders such as hepatic steatosis, cardiovascular disease, diabetes, and obesity as well. Furthermore, this phenolic acid (CGA) causes hepatoprotective effects by protecting animals from chemical or lipopolysaccharide-induced injuries. The hypocholesterolemic influence of CGA can result from the altered metabolism of nutrients, including amino acids, glucose and fatty acids (FA). The purpose of this review was to broaden the scope of knowledge of researchers to conduct more studies on this subject to both unveil and optimize its biological and pharmacological effects. As a result, CGA may be practically used as a natural safeguard food additive to replace the synthetic antibiotics and thereby reduce the medicinal cost.
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              Amino acid transport across mammalian intestinal and renal epithelia.

              The transport of amino acids in kidney and intestine is critical for the supply of amino acids to all tissues and the homeostasis of plasma amino acid levels. This is illustrated by a number of inherited disorders affecting amino acid transport in epithelial cells, such as cystinuria, lysinuric protein intolerance, Hartnup disorder, iminoglycinuria, dicarboxylic aminoaciduria, and some other less well-described disturbances of amino acid transport. The identification of most epithelial amino acid transporters over the past 15 years allows the definition of these disorders at the molecular level and provides a clear picture of the functional cooperation between transporters in the apical and basolateral membranes of mammalian epithelial cells. Transport of amino acids across the apical membrane not only makes use of sodium-dependent symporters, but also uses the proton-motive force and the gradient of other amino acids to efficiently absorb amino acids from the lumen. In the basolateral membrane, antiporters cooperate with facilitators to release amino acids without depleting cells of valuable nutrients. With very few exceptions, individual amino acids are transported by more than one transporter, providing backup capacity for absorption in the case of mutational inactivation of a transport system.
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                Author and article information

                Contributors
                Journal
                Oxid Med Cell Longev
                Oxid Med Cell Longev
                OMCL
                Oxidative Medicine and Cellular Longevity
                Hindawi
                1942-0900
                1942-0994
                2022
                12 March 2022
                : 2022
                : 6316611
                Affiliations
                1National Engineering Laboratory for Pollution Control and Waste Utilization in Livestock and Poultry Production, Hunan Provincial Key Laboratory of Animal Nutritional Physiology and Metabolic Process, Key Laboratory of Agro-ecological Process in Subtropical Region, Institute of Subtropical Agriculture, Chinese Academy of Sciences, Changsha, Hunan 410125, China
                2Hunan Provincial Key Laboratory of Animal Intestinal Function and Regulation, Hunan International Joint Laboratory of Animal Intestinal Ecology and Health, Laboratory of Animal Nutrition and Human Health, School of Life Sciences, Hunan Normal University, Changsha, Hunan 410081, China
                3University of Chinese Academy of Sciences, Beijing 100049, China
                4College of Animal Science and Technology, Hunan Agricultural University, Changsha, Hunan 410128, China
                Author notes

                Academic Editor: Abdur Rauf

                Author information
                https://orcid.org/0000-0003-1669-613X
                https://orcid.org/0000-0002-0040-9784
                https://orcid.org/0000-0003-4074-3768
                https://orcid.org/0000-0002-0768-421X
                https://orcid.org/0000-0002-0065-4085
                Article
                10.1155/2022/6316611
                8934221
                35313639
                d60ad67a-ba6f-4c00-b62c-db6881e37477
                Copyright © 2022 Wenlong Wang et al.

                This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

                History
                : 15 July 2021
                : 10 December 2021
                : 21 February 2022
                Funding
                Funded by: National Natural Science Foundation of China
                Award ID: 31972582
                Award ID: 32102572
                Funded by: Science and Technology Program of Hunan Province
                Award ID: 2021RC4039
                Funded by: Distinguished Young Scholar Foundation of Hunan Province
                Award ID: 2020JJ2030
                Funded by: Key R & D Program of Hunan Province
                Award ID: 2022NK2026
                Funded by: Science and Technology Projects of Changsha City
                Award ID: kq1801059
                Funded by: Youth Innovation Promotion Association CAS
                Award ID: Y202079
                Funded by: Earmarked Fund for China Agriculture Research System
                Award ID: CARS-35
                Funded by: Hunan Provincial Innovation Foundation for Postgraduate
                Award ID: CX2017B183
                Funded by: Innovation Team in Key Area “Innovation Team of Physiology and Metabolism and Body Health in Pig”
                Award ID: 2019RS3022
                Funded by: Hunan Province Key Laboratory of Animal Nutritional Physiology and Metabolic Process
                Categories
                Research Article

                Molecular medicine
                Molecular medicine

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