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Int. J. Mol. Sci. 2018, 19(12), 3852; https://doi.org/10.3390/ijms19123852

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

1
Laboratory of Molecular Pathology and Metabolic Disease, Faculty of Pharmaceutical Sciences, Tokyo University of Science, Chiba 278-8510, Japan
2
Translational Research Center, Research Institute of Science and Technology, Tokyo University of Science, Chiba 278-8510, Japan
3
Division of Cancer Pathophysiology, National Cancer Research Institute, Tokyo 104-0045, Japan
4
Tsumura Kampo Research Laboratories, Tsumura & Co., Ibaraki 300-1192, Japan
5
Division of Supportive Care Research, National Cancer Center Exploratory Oncology Research and Clinical Trial Center, Tokyo 104-0045, Japan
6
Division of Pathological Biochemistry, Faculty of Pharmaceutical Sciences, Sanyo-Onoda City University, Yamaguchi 756-0884, Japan
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Received: 6 September 2018 / Revised: 17 November 2018 / Accepted: 24 November 2018 / Published: 3 December 2018
(This article belongs to the Special Issue Transcriptional Regulation in Lipid Metabolism)
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Abstract

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. View Full-Text
Keywords: cancer cachexia; caloric restriction; sterol regulatory element-binding transcription factor 1c; rikkunshito cancer cachexia; caloric restriction; sterol regulatory element-binding transcription factor 1c; rikkunshito
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Sudo, Y.; Otsuka, H.; Miyakawa, R.; Goto, A.; Kashiwase, Y.; Terawaki, K.; Miyano, K.; Hirao, Y.; Taki, K.; Tagawa, R.; Kobayashi, M.; Okita, N.; Uezono, Y.; Higami, Y. Differential Metabolic Responses to Adipose Atrophy Associated with Cancer Cachexia and Caloric Restriction in Rats and the Effect of Rikkunshito in Cancer Cachexia. Int. J. Mol. Sci. 2018, 19, 3852.

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