α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube

There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced...

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Main Authors: Koichiro Sumi, Misato Sakuda, Kinuyo Munakata, Kentaro Nakamura, Kinya Ashida
Format: Article
Language:English
Published: MDPI AG 2021-07-01
Series:Nutrients
Subjects:
Online Access:https://www.mdpi.com/2072-6643/13/7/2391
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author Koichiro Sumi
Misato Sakuda
Kinuyo Munakata
Kentaro Nakamura
Kinya Ashida
author_facet Koichiro Sumi
Misato Sakuda
Kinuyo Munakata
Kentaro Nakamura
Kinya Ashida
author_sort Koichiro Sumi
collection DOAJ
description There is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.
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spelling doaj.art-735ace407a83444f893e1ea80416d63e2023-11-22T04:36:47ZengMDPI AGNutrients2072-66432021-07-01137239110.3390/nu13072391α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 MyotubeKoichiro Sumi0Misato Sakuda1Kinuyo Munakata2Kentaro Nakamura3Kinya Ashida4Food Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanFood Microbiology and Function Research Laboratories, R&D Division, Meiji Co. Ltd., 1-29-1 Nanakuni, Hachiouji, Tokyo 192-0919, JapanThere is ongoing debate as to whether or not α-hydroxyisocaproic acid (HICA) positively regulates skeletal muscle protein synthesis resulting in the gain or maintenance of skeletal muscle. We investigated the effects of HICA on mouse C2C12 myotubes under normal conditions and during cachexia induced by co-exposure to TNFα and IFNγ. The phosphorylation of AMPK or ERK1/2 was significantly altered 30 min after HICA treatment under normal conditions. The basal protein synthesis rates measured by a deuterium-labeling method were significantly lowered by the HICA treatment under normal and cachexic conditions. Conversely, myotube atrophy induced by TNFα/IFNγ co-exposure was significantly improved by the HICA pretreatment, and this improvement was accompanied by the inhibition of iNOS expression and IL-6 production. Moreover, HICA also suppressed the TNFα/IFNγ co-exposure-induced secretion of 3-methylhistidine. These results demonstrated that HICA decreases basal protein synthesis under normal or cachexic conditions; however, HICA might attenuate skeletal muscle atrophy via maintaining a low level of protein degradation under cachexic conditions.https://www.mdpi.com/2072-6643/13/7/2391α-hydroxyisocaproic acidTNFαInterferon-γAMPKERKprotein synthesis
spellingShingle Koichiro Sumi
Misato Sakuda
Kinuyo Munakata
Kentaro Nakamura
Kinya Ashida
α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
Nutrients
α-hydroxyisocaproic acid
TNFα
Interferon-γ
AMPK
ERK
protein synthesis
title α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
title_full α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
title_fullStr α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
title_full_unstemmed α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
title_short α-Hydroxyisocaproic Acid Decreases Protein Synthesis but Attenuates TNFα/IFNγ Co-Exposure-Induced Protein Degradation and Myotube Atrophy via Suppression of iNOS and IL-6 in Murine C2C12 Myotube
title_sort α hydroxyisocaproic acid decreases protein synthesis but attenuates tnfα ifnγ co exposure induced protein degradation and myotube atrophy via suppression of inos and il 6 in murine c2c12 myotube
topic α-hydroxyisocaproic acid
TNFα
Interferon-γ
AMPK
ERK
protein synthesis
url https://www.mdpi.com/2072-6643/13/7/2391
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