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Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia

Despite the similar phenotypes, including weight loss, reduction of food intake, and lower adiposity, associated with caloric restriction (CR) and cancer cachexia (CC), CC is a progressive wasting syndrome, while mild CR improves whole body metabolism. In the present study, we compared adipose metab...

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Autores principales: Sudo, Yuka, Otsuka, Hiroki, Miyakawa, Ryota, Goto, Akifumi, Kashiwase, Yohei, Terawaki, Kiyoshi, Miyano, Kanako, Hirao, Yuto, Taki, Kanari, Tagawa, Ryoma, Kobayashi, Masaki, Okita, Naoyuki, Uezono, Yasuhito, Higami, Yoshikazu
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2018
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321026/
https://www.ncbi.nlm.nih.gov/pubmed/30513935
http://dx.doi.org/10.3390/ijms19123852
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author Sudo, Yuka
Otsuka, Hiroki
Miyakawa, Ryota
Goto, Akifumi
Kashiwase, Yohei
Terawaki, Kiyoshi
Miyano, Kanako
Hirao, Yuto
Taki, Kanari
Tagawa, Ryoma
Kobayashi, Masaki
Okita, Naoyuki
Uezono, Yasuhito
Higami, Yoshikazu
author_facet Sudo, Yuka
Otsuka, Hiroki
Miyakawa, Ryota
Goto, Akifumi
Kashiwase, Yohei
Terawaki, Kiyoshi
Miyano, Kanako
Hirao, Yuto
Taki, Kanari
Tagawa, Ryoma
Kobayashi, Masaki
Okita, Naoyuki
Uezono, Yasuhito
Higami, Yoshikazu
author_sort Sudo, Yuka
collection PubMed
description Despite the similar phenotypes, including weight loss, reduction of food intake, and lower adiposity, associated with caloric restriction (CR) and cancer cachexia (CC), CC is a progressive wasting syndrome, while mild CR improves whole body metabolism. In the present study, we compared adipose metabolic changes in a novel rat model of CC, mild CR (70% of the food intake of control rats, which is similar to the food consumption of CC rats), and severe CR (30% of the food intake of controls). We show that CC and severe CR are associated with much smaller adipocytes with significantly lower mitochondrial DNA content; but, that mild CR is not. CC and both mild and severe CR similarly upregulated proteins involved in lipolysis. CC also downregulated proteins involved in fatty acid biosynthesis, but mild CR upregulated these. These findings suggest that CC might impair de novo fatty acid biosynthesis and reduce mitochondrial biogenesis, similar to severe CR. We also found that rikkunshito, a traditional Japanese herbal medicine, does not ameliorate the enhanced lipolysis and mitochondrial impairment, but rather, rescues de novo fatty acid biosynthesis, suggesting that rikkunshito administration might have partially similar effects to mild CR.
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spelling pubmed-63210262019-01-07 Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia Sudo, Yuka Otsuka, Hiroki Miyakawa, Ryota Goto, Akifumi Kashiwase, Yohei Terawaki, Kiyoshi Miyano, Kanako Hirao, Yuto Taki, Kanari Tagawa, Ryoma Kobayashi, Masaki Okita, Naoyuki Uezono, Yasuhito Higami, Yoshikazu Int J Mol Sci Article Despite the similar phenotypes, including weight loss, reduction of food intake, and lower adiposity, associated with caloric restriction (CR) and cancer cachexia (CC), CC is a progressive wasting syndrome, while mild CR improves whole body metabolism. In the present study, we compared adipose metabolic changes in a novel rat model of CC, mild CR (70% of the food intake of control rats, which is similar to the food consumption of CC rats), and severe CR (30% of the food intake of controls). We show that CC and severe CR are associated with much smaller adipocytes with significantly lower mitochondrial DNA content; but, that mild CR is not. CC and both mild and severe CR similarly upregulated proteins involved in lipolysis. CC also downregulated proteins involved in fatty acid biosynthesis, but mild CR upregulated these. These findings suggest that CC might impair de novo fatty acid biosynthesis and reduce mitochondrial biogenesis, similar to severe CR. We also found that rikkunshito, a traditional Japanese herbal medicine, does not ameliorate the enhanced lipolysis and mitochondrial impairment, but rather, rescues de novo fatty acid biosynthesis, suggesting that rikkunshito administration might have partially similar effects to mild CR. MDPI 2018-12-03 /pmc/articles/PMC6321026/ /pubmed/30513935 http://dx.doi.org/10.3390/ijms19123852 Text en © 2018 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Sudo, Yuka
Otsuka, Hiroki
Miyakawa, Ryota
Goto, Akifumi
Kashiwase, Yohei
Terawaki, Kiyoshi
Miyano, Kanako
Hirao, Yuto
Taki, Kanari
Tagawa, Ryoma
Kobayashi, Masaki
Okita, Naoyuki
Uezono, Yasuhito
Higami, Yoshikazu
Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia
title Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia
title_full Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia
title_fullStr Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia
title_full_unstemmed Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia
title_short Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia
title_sort differential metabolic responses to adipose atrophy associated with cancer cachexia and caloric restriction in rats and the effect of rikkunshito in cancer cachexia
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6321026/
https://www.ncbi.nlm.nih.gov/pubmed/30513935
http://dx.doi.org/10.3390/ijms19123852
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