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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Bibliographic Details
Published in:	International journal of molecular sciences Vol. 19; no. 12; p. 3852
Main Authors:	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
Format:	Journal Article
Language:	English
Published:	Switzerland MDPI AG 03-12-2018 MDPI
Subjects:	Adipocytes Adipose tissue Anorexia Atrophy Biosynthesis Body weight loss Cachexia caloric restriction Cancer cancer cachexia Cytokines Dietary restrictions Enzymes Fatty acids Food Food consumption Food intake Gastric cancer Herbal medicine Lipolysis Metabolic response Metabolism Mitochondrial DNA Phenotypes Proteins rikkunshito Rodents sterol regulatory element-binding transcription factor 1c Tumors Weight loss Weight reduction sterol regulatory element-binding transcription factor 1c caloric restriction rikkunshito cancer cachexia
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Summary:	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.
Bibliography:	ObjectType-Article-1 SourceType-Scholarly Journals-1 ObjectType-Feature-2 content type line 23 These authors contributed equally to this work.
ISSN:	1422-0067 1661-6596 1422-0067
DOI:	10.3390/ijms19123852