Analysis of liver metabolism in a rat model of heart failure

Takao Kato, Shinichiro Niizuma, Yasutaka Inuzuka, Tsuneaki Kawashima, Junji Okuda, Akira Kawamoto, Yodo Tamaki, Yoshitaka Iwanaga, Tomoyoshi Soga, Toru Kita, Takeshi Kimura, Tetsuo Shioi

Research output: Contribution to journalArticlepeer-review

23 Citations (Scopus)

Abstract

Background: Cachexia, namely body wasting, is a common complication in cases of congestive heart failure (CHF). Although, neurohumoral and immune abnormalities are associated with the condition, precisely how the imbalance of catabolism and anabolism is responsible for the wasting process is not known. Methods: We analyzed markers of cachexia in Dahl salt-sensitive rats which show marked hypertension with preserved systolic function at 11 weeks and CHF at 17-19 weeks of age. We also analyzed the change in hepatic metabolism associated with CHF since liver plays a central role in the systemic regulation of catabolism and anabolism. Results: In CHF rats, a failure to grow was observed and blood hepatic protein levels were decreased associated with increased blood proinflammatory cytokine levels, indicating that Dahl rats serve as a model of cardiac cachexia. Food intake was reduced, and blood sugar and insulin levels were decreased. Despite the apparent fasting condition, blood fatty acid levels were decreased and triglycerides levels were increased. In CHF rats, liver incorporated more glucose, the gene expression related to gluconeogenesis was decreased, the gene expression related to lipogenesis was increased, and the triglyceride content of the liver was increased. The paradoxical production of triglycerides synthesis in fasting rats was associated with a proinflammatory response in liver. Conclusions: The Dahl salt-sensitive rat can be used as a model of cardiac cachexia. The cachexia was associated with abnormal hepatic metabolism that might work as a maladaptive response during the progression of CHF.

Original languageEnglish
Pages (from-to)130-136
Number of pages7
JournalInternational Journal of Cardiology
Volume161
Issue number3
DOIs
Publication statusPublished - 2012 Nov 29

Keywords

  • Cachexia
  • Heart failure
  • Inflammation
  • Lipogenesis
  • Liver

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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