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.

Metabolomics differences between silkworms (Bombyx mori) reared on fresh mulberry (Morus) leaves or artificial diets

“…GC-MS is suitable for the analysis of small-molecule, thermostable, volatile, gasifiable compounds, while LC-MS can analyze compounds with higher polarity, higher relative molecular mass, and poor thermal stability. Numerous studies have shown how these techniques may be used to complement each other 34 – 36 . Zhou et al .…”

Loss of the clock gene PER2 is associated with cancer development and altered expression of important tumor-related genes in oral cancer

“…CCGs are involved in various physiological activities, including cell proliferation, apoptosis, cell cycling, metabolism, endocrine signaling and immunity (4)(5)(6)(7)(8). As a result, abnormal expression of clock genes can lead to a variety of diseases, including endocrine disorders, cardiovascular diseases and tumors (9)(10)(11)(12).…”

Networks Underpinning Symbiosis Revealed Through Cross-Species eQTL Mapping

“…However, it is now clear that changes in gene expression levels also can determine phenotypic outcomes ( e.g. , Bakar et al 2015 ; Rose et al 2016 ; Schweizer et al 2016 ; Lotan et al 2017 ; Tao et al 2017 ). Because of this, connections between genetic polymorphisms and changes in expression levels revealed by eQTL mapping provide powerful insights into the mechanistic pathways underlying the genotype–phenotype relationship ( e.g.…”