Talks：

Roles of circadian-clock system in insulin resistance

Name：

謝坤叡(Kun-Ruey Shieh)

Position：

Professor/Vice Head/Dean of Student Affairs

Affiliation：

Department of Physiology, School of Medicine, Office of Student Affairs, Tzu Chi University

Email：

krshieh@mail.tcu.edu.tw

Photo：

Research Interests：

Chronobiology, Neuroscience, Gastroenterology, Endocrinology, Animal Behavior

Selected Publications：

◆ Shieh KR: Distribution of the rhythm-related genes, rPeriod1, rPeriod2, and rClock, in the rat brain. Neuroscience 118: 831-843, 2003. ◆ Shieh KR, Yang SC, Lu XY, Akil H, Watson SJ: Diurnal rhythmic expression of the rhythm-related genes, rPeriod1, rPeriod2, and rClock, in the rat brain. Journal of Biomedical Science 12: 209-217, 2005. ◆ Hsieh MC, Yang SC, Tseng HL, Hwang LL, Chen CT, Shieh KR: Abnormal expressions of circadian-clock and circadian clock-controlled genes in the livers and kidneys of long term, high-fat diet-treated mice. International Journal of Obesity 34: 227-239, 2010. ◆ Yang SC, Tseng HL, Shieh KR: Circadian-clock system in mouse liver affected by insulin resistance. Chronobiology International 30: 796-810, 2013. ◆ Tseng HL, Yang SC, Shieh KR: Hepatic circadian-clock system altered by insulin resistance, diabetes and insulin sensitizer in mice. PLOS One 10: e0120380, 2015. ◆ Yang SC, Chen CL, Yi CH, Liu TT, Shieh KR: Changes in gene expression patterns of circadian-clock, transient receptor potential vanilloid-1 and nerve growth factor in inflamed human esophagus. Scientific Reports 5: 13602, 2015.

Abstract：

Circadian rhythmicity is displayed in behavioral activities, hormonal secretion, and the expression of genes and proteins in most organisms on earth. These rhythms serve a vital role by matching numerous physiological functions to anticipated environmental demands. Circadian rhythm is driven by the molecular circadian-clock system, which includes Bmal1 (brain and muscle aryl-hydrocarbon receptor nuclear translocator-like protein-1), Clock (circadian locomotor output cycles kaput), Per1 (period 1), Per2, Per3, Cry1 (cryptochrome 1) and Cry2. This system involves interacting positive and negative transcriptional/translational feedback loops that are composed of a set of circadian-clock genes that encode highly conserved transcription factors and enzymes that generate rhythmic expression. This circadian-clock system exists throughout the entire body, including the heart, lung, kidney and liver, although the physiological role of circadian-clock genes in peripheral tissues is not fully understood. However, the impact on skeletal muscle, pancreatic islets and adipose tissues with respect to the regulation of glucose metabolism is becoming clearer. The liver aids the organism via temporally tuning expression of genes in relation to food supply. Metabolic regulation is a dynamic process within the hepatic system and is triggered by sensing nutrient stimuli and producing various nutrients. Thus, the liver is critical in regulating and maintaining glucose homeostasis, including gluconeogenesis, and the circadian-clock system is thought to be involved in these processes which coordinate internal glucose metabolism based on external stimuli. Our studies indicate that obesity induced by high-fat diet alters the circadian-clock system, and obesity and metabolic syndrome are highly correlated with the expressions of circadian-clock genes and their downstream, circadian-clock controlled genes. The hepatic circadian-clock system is sensitive to insulin resistance, and that treatment with insulin sensitizers resolves changes in the circadian-clock system in a timely manner, and even delays the severity of diabetic conditions. Together, these results support an essential role for the hepatic circadian-clock system in the coordinated regulation and/or response of metabolic pathways.