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Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice

A decrease in TCA cycle activity may lead to impaired nutrition metabolism and cellular energy shortage. Herein, we aimed to characterize the detailed metabolic changes that compensate for energy shortages in energy-consuming organs (heart and skeletal muscles) in mice with knockout of citrate synth...

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Autores principales: Sumi, Kanako, Hatanaka, Yuiko, Takahashi, Reina, Wada, Naoko, Ono, Chihiro, Sakamoto, Yuri, Sone, Hirohito, Iida, Kaoruko
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Frontiers Media S.A. 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302927/
https://www.ncbi.nlm.nih.gov/pubmed/35873436
http://dx.doi.org/10.3389/fnut.2022.925908
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author Sumi, Kanako
Hatanaka, Yuiko
Takahashi, Reina
Wada, Naoko
Ono, Chihiro
Sakamoto, Yuri
Sone, Hirohito
Iida, Kaoruko
author_facet Sumi, Kanako
Hatanaka, Yuiko
Takahashi, Reina
Wada, Naoko
Ono, Chihiro
Sakamoto, Yuri
Sone, Hirohito
Iida, Kaoruko
author_sort Sumi, Kanako
collection PubMed
description A decrease in TCA cycle activity may lead to impaired nutrition metabolism and cellular energy shortage. Herein, we aimed to characterize the detailed metabolic changes that compensate for energy shortages in energy-consuming organs (heart and skeletal muscles) in mice with knockout of citrate synthase (CS), an important enzyme in the TCA cycle. CS hetero knockout (CS +/−) mice and wild-type mice were fed a low-carbohydrate ketogenic diet (LCKD) or high-fat, high-carbohydrate diet (HFHCD) to induce metabolic changes. Body weight, blood serum parameters, metabolic gene expression, and adenosine triphosphate (ATP) levels were measured in the heart and skeletal muscles. Glycogen content, anabolic and catabolic biomarkers, and morphological changes were also assessed in the skeletal muscles. After diet feeding, there were no differences observed in the body weight and blood serum parameters between wild-type and CS +/− mice. The cardiac expression of genes related to the utilization of fatty acids, monocarboxylates, and branched amino acids increased in LCKD-fed CS +/− mice. In contrast, no significant differences in gene expression were observed in the muscles of LCKD-fed mice or the heart and muscles of HFHCD-fed mice. ATP levels decreased only in the skeletal muscles of LCKD-fed CS +/− mice. Additionally, the decrease in glycogen content, suppression of p70 S6 kinase, and presence of type I fiber atrophy were observed in the muscles of LCKD-fed CS +/− mice. These results suggest that the energy-consuming organs with CS insufficiency may undergo tissue-specific adaption to compensate for energy shortages when the carbohydrate supply is limited.
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spelling pubmed-93029272022-07-22 Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice Sumi, Kanako Hatanaka, Yuiko Takahashi, Reina Wada, Naoko Ono, Chihiro Sakamoto, Yuri Sone, Hirohito Iida, Kaoruko Front Nutr Nutrition A decrease in TCA cycle activity may lead to impaired nutrition metabolism and cellular energy shortage. Herein, we aimed to characterize the detailed metabolic changes that compensate for energy shortages in energy-consuming organs (heart and skeletal muscles) in mice with knockout of citrate synthase (CS), an important enzyme in the TCA cycle. CS hetero knockout (CS +/−) mice and wild-type mice were fed a low-carbohydrate ketogenic diet (LCKD) or high-fat, high-carbohydrate diet (HFHCD) to induce metabolic changes. Body weight, blood serum parameters, metabolic gene expression, and adenosine triphosphate (ATP) levels were measured in the heart and skeletal muscles. Glycogen content, anabolic and catabolic biomarkers, and morphological changes were also assessed in the skeletal muscles. After diet feeding, there were no differences observed in the body weight and blood serum parameters between wild-type and CS +/− mice. The cardiac expression of genes related to the utilization of fatty acids, monocarboxylates, and branched amino acids increased in LCKD-fed CS +/− mice. In contrast, no significant differences in gene expression were observed in the muscles of LCKD-fed mice or the heart and muscles of HFHCD-fed mice. ATP levels decreased only in the skeletal muscles of LCKD-fed CS +/− mice. Additionally, the decrease in glycogen content, suppression of p70 S6 kinase, and presence of type I fiber atrophy were observed in the muscles of LCKD-fed CS +/− mice. These results suggest that the energy-consuming organs with CS insufficiency may undergo tissue-specific adaption to compensate for energy shortages when the carbohydrate supply is limited. Frontiers Media S.A. 2022-07-07 /pmc/articles/PMC9302927/ /pubmed/35873436 http://dx.doi.org/10.3389/fnut.2022.925908 Text en Copyright © 2022 Sumi, Hatanaka, Takahashi, Wada, Ono, Sakamoto, Sone and Iida. https://creativecommons.org/licenses/by/4.0/This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.
spellingShingle Nutrition
Sumi, Kanako
Hatanaka, Yuiko
Takahashi, Reina
Wada, Naoko
Ono, Chihiro
Sakamoto, Yuri
Sone, Hirohito
Iida, Kaoruko
Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice
title Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice
title_full Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice
title_fullStr Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice
title_full_unstemmed Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice
title_short Citrate Synthase Insufficiency Leads to Specific Metabolic Adaptations in the Heart and Skeletal Muscles Upon Low-Carbohydrate Diet Feeding in Mice
title_sort citrate synthase insufficiency leads to specific metabolic adaptations in the heart and skeletal muscles upon low-carbohydrate diet feeding in mice
topic Nutrition
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9302927/
https://www.ncbi.nlm.nih.gov/pubmed/35873436
http://dx.doi.org/10.3389/fnut.2022.925908
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