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Per2 Gene Expressions in the Suprachiasmatic Nucleus and Liver Differentially Respond to Nutrition Factors in Rats

Hiroshi Iwanaga, MD^*, Masahiko Yano, MD, PhD^*, Hirofumi Miki, MD, PhD^*, Kazuyuki Okada, MD^*, Takashi Azama, MD^*, Syuji Takiguchi, MD^*, Yoshiyuki Fujiwara, MD, PhD^*, Takushi Yasuda, MD, PhD^*, Mitsuo Nakayama, PhD, Masaru Kobayashi, PhD, Katsutaka Oishi, PhD, Norio Ishida, PhD^,,||, Katsuya Nagai, MD, PhD^¶ and Morito Monden, MD, PhD^*,||

From the ^* Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, Suita, Japan; Pharmacology Section, Nutrition Research Institute, Otsuka Pharmaceutical Factory, Inc, Naruto, Japan; Clock Cell Biology Group, National Institute of Advanced Industrial Science and Technology, AIST, Tsukaba, Japan; Department of Biomolecular Engineering, Tokyo Institute of Technology, Yokohama, Japan; ^|| Center for Interdisciplinary Research, Tohoku University, Sendai, Japan; and^¶ Division of Protein Metabolism, Institute for Protein Research, Osaka University, Suita, Japan

Correspondence: M. Yano, Department of Surgery and Clinical Oncology, Osaka University Graduate School of Medicine, 2-2-E2, Yamada-Oka, Suita, Osaka 565-0871, Japan. Electronic mail may be sent to myano{at}surg2.med.osaka-u.ac.jp.

Background: We previously reported that parenteral nutrition (PN) altered the circadian rhythm of clock gene expression in the suprachiasmatic nucleus (SCN) and liver of rats. The present study was designed to investigate what factor(s) in the PN solution causes the alteration. Methods: Male Wistar rats, kept under light and dark conditions, were divided into 4 groups after cannulation. The sham operation group received saline solution from 8 AM to 8 PM at the rate of 36 mL/kg/12 hours. The glucose, amino acid, and saline groups received a glucose solution (20% wt/vol glucose, 261 kcal/kg/d, Na⁺ 50 meq/L and Cl^– 50 meq/L), an amino acid solution (4.3% wt/vol 1.78 gN/kg/d, Na +50 meq/L and Cl^– 50 meq/L) and a saline solution from 8 AM to 8 PM at a rate of 240 mL/kg/12 hours, respectively. Rats were killed every 4 hours (9 AM = Zeitgeber Time (ZT) 02, 1 PM = ZT06, 5 PM = ZT10, 9 PM = ZT14, 1 AM = ZT18, 5 AM = ZT22, n = 3 at each point), and brain and liver samples were removed. rPer2 expression in the SCN and liver was analyzed by in situ hybridization and Northern blotting, respectively. Results: Compared with the sham-operation rats, the peak time of rPer2 expression in the SCN was significantly affected by glucose, amino acid, and saline solutions. Among them, glucose-group rats showed the rPer2 expression most similar to that of diurnal PN. On the other hand, the rPer2 expression in the liver was shifted in the glucose and amino-acid-solution groups. The pattern of rPer2 expressions in the amino acid group was most similar to that of the diurnal PN group. Conclusions: These results indicate that the most potent entrainer for the SCN clock is glucose, whereas that for the liver is amino acid.

Journal of Parenteral and Enteral Nutrition, Vol. 29, No. 3, 157-161 (2005)
DOI: 10.1177/0148607105029003157


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