Very low protein diet enhances inflammation, malnutrition, and vascular calcification in uremic rats

Shunsuke Yamada, Masanori Tokumoto, Narihito Tatsumoto, Kazuhiko Tsuruya, Takanari Kitazono, Hiroaki Ooboshi

研究成果: ジャーナルへの寄稿学術誌査読

20 被引用数 (Scopus)


Aims Clinical studies have shown that very low protein diet (VLPD) has negative effects on long-term survival. It remains unclear why VLPD induces premature death. The present study determined the underlying mechanism whereby VLPD exerts its harmful effects on uremic rats. Main methods Rats were divided into four groups and fed a normal diet or diets containing 0.3% adenine and low/normal protein with high/low phosphate. After 6 weeks, body weight, urinary biochemistry (creatinine and phosphate), serum biochemical parameters (urea, creatinine, fibroblast growth factor 23, albumin, and fetuin-A), systemic inflammatory markers (serum tumor necrosis factor-alpha and urinary 8-hydroxy-2′-deoxyguanosine), calcium content in the aorta, and serum calcium-phosphate precipitates were evaluated. Hepatic mRNA levels were also determined. Key findings Rats fed the diet containing 0.3% adenine developed severe azotemia. Rats fed VLPD developed malnutrition (decreases in body weight, serum albumin and fetuin-A levels, and urinary creatinine excretion) and systemic inflammation (increases in serum tumor necrosis factor-α and urinary 8-hydroxy-2′-deoxyguanosine) independent of phosphate status. VLPD decreased the serum fetuin-A level and hepatic fetuin-A synthesis and increased serum calcium-phosphate precipitates, a marker of calciprotein particle. A high-phosphate diet induced arterial medial calcification, which was enhanced by VLPD. Serum calcium-phosphate precipitate levels were correlated with the degree of inflammation, malnutrition, and aortic calcium content. Dietary phosphate restriction prevented VLPD-enhanced vascular calcification, but could not halt inflammation and malnutrition induced by VLPD. Significance VLPD enhances inflammation, malnutrition, and vascular calcification in uremic rats, among which only vascular calcification is prevented by dietary phosphate restriction.

ジャーナルLife Sciences
出版ステータス出版済み - 2月 1 2016

!!!All Science Journal Classification (ASJC) codes

  • 薬理学、毒性学および薬学一般
  • 生化学、遺伝学、分子生物学一般


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