title: Inhibition of expression of the circadian clock gene Period causes metabolic abnormalities including repression of glycometabolism in Bombyx mori cells.
abstract: Abnormalities in the circadian clock system are known to affect the body's metabolic functions, though the molecular mechanisms responsible remain uncertain. In this study, we achieved continuous knockdown of B. mori Period (BmPer) gene expression in the B. mori ovary cell line (BmN), and generated a Per-KD B. mori model with developmental disorders including small individual cells and slow growth. We conducted cell metabolomics assays by gas chromatography/liquid chromatography-mass spectrometry and showed that knockdown of BmPer gene expression resulted in significant inhibition of glycometabolism. Amino acids that used glucose metabolites as a source were also down-regulated, while lipid metabolism and nucleotide metabolism were significantly up-regulated. Metabolite correlation analysis showed that pyruvate and lactate were closely related to glycometabolism, as well as to metabolites such as aspartate, alanine, and xanthine in other pathways. Further validation experiments showed that the activities of the key enzymes of glucose metabolism, hexokinase, phosphofructokinase, and citrate synthase, were significantly decreased and transcription of their encoding genes, as well as that of pyruvate kinase, were also significantly down-regulated. We concluded that inhibition of the circadian clock gene BmPer repressed glycometabolism, and may be associated with changes in cellular amino acid metabolism, and in cell growth and development.
authors.affiliation: School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.|Institute of Agricultural Biotechnology &Ecology (IABE), Soochow University, Suzhou 215123, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Tao
authors.affiliation: School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.|Institute of Agricultural Biotechnology &Ecology (IABE), Soochow University, Suzhou 215123, China.
authors.forename: Xue
authors.initials: X
authors.lastname: Li
authors.affiliation: School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.|Institute of Agricultural Biotechnology &Ecology (IABE), Soochow University, Suzhou 215123, China.
authors.forename: Jian-Feng
authors.initials: JF
authors.lastname: Qiu
authors.affiliation: School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.|Institute of Agricultural Biotechnology &Ecology (IABE), Soochow University, Suzhou 215123, China.
authors.forename: Wen-Zhao
authors.initials: WZ
authors.lastname: Cui
authors.affiliation: School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.|Institute of Agricultural Biotechnology &Ecology (IABE), Soochow University, Suzhou 215123, China.|National Engineering Laboratory for Modern Silk (NEAER), Soochow University, Suzhou 215123, China.
authors.forename: Yang-Hu
authors.initials: YH
authors.lastname: Sima
authors.affiliation: School of Biology and Basic Medical Sciences, Medical College, Soochow University, Suzhou 215123, China.|Institute of Agricultural Biotechnology &Ecology (IABE), Soochow University, Suzhou 215123, China.|National Engineering Laboratory for Modern Silk (NEAER), Soochow University, Suzhou 215123, China.
authors.forename: Shi-Qing
authors.initials: SQ
authors.lastname: Xu
mesh_terms: D000818:Animals; D012831:Bombyx / Q000235:genetics* / Q000378:metabolism*; D050260:Carbohydrate Metabolism; D002460:Cell Line; D002853:Chromatography, Liquid; D057906:Circadian Clocks / Q000235:genetics*; D002940:Circadian Rhythm / Q000235:genetics; D004734:Energy Metabolism; D008401:Gas Chromatography-Mass Spectrometry; D015870:Gene Expression; D055785:Gene Knockdown Techniques; D005947:Glucose / Q000378:metabolism; D019476:Insect Proteins / Q000235:genetics; D053858:Metabolic Networks and Pathways; D055442:Metabolome; D055432:Metabolomics / Q000379:methods; D056950:Period Circadian Proteins / Q000235:genetics*
chemical_list: D019476:Insect Proteins; D056950:Period Circadian Proteins; D005947:Glucose