24:T541,Accumulating evidence suggests that the circadian clock is closely associated with metabolic regulation. However, whether an impaired circadian clock is a direct cause of metabolic dysregulation such as body weight gain is not clearly understood. In this study, we demonstrate that body weight gain in mice is not significantly changed by restricting feeding period to daytime or nighttime. The expression of peripheral circadian clock genes was altered by feeding period restriction, while the expression of light-regulated hypothalamic circadian clock genes was unaffected by either a normal chow diet (NCD) or a high-fat diet (HFD). In the liver, the expression pattern of circadian clock genes, including Bmal1, Clock, and Per2, was changed by different feeding period restrictions. Moreover, the expression of lipogenic genes, gluconeogenic genes, and fatty acid oxidation-related genes in the liver was also altered by feeding period restriction. Given that feeding period restriction does not affect body weight gain with a NCD or HFD, it is likely that the amount of food consumed might be a crucial factor in determining body weight. Collectively, these data suggest that feeding period restriction modulates the expression of peripheral circadian clock genes, which is uncoupled from light-sensitive hypothalamic circadian clock genes.25:T44d,Oxygen is a key molecule for efficient energy production in living organisms. Although aerobic organisms have adaptive processes to survive in low-oxygen environments, it is poorly understood how lipolysis, the first step of energy production from stored lipid metabolites, would be modulated during hypoxia. Here, we demonstrate that fasting-induced lipolysis is downregulated by hypoxia through the hypoxia-inducible factor (HIF) signaling pathway. In Caenorhabditis elegans and mammalian adipocytes, hypoxia suppressed protein kinase A (PKA)-stimulated lipolysis, which is evolutionarily well conserved. During hypoxia, the levels of PKA activity and adipose triglyceride lipase (ATGL) protein were downregulated, resulting in attenuated fasting-induced lipolysis. In worms, HIF stabilization was sufficient to moderate the suppressive effect of hypoxia on lipolysis through ATGL and PKA inhibition. These data suggest that HIF activation under hypoxia plays key roles in the suppression of lipolysis, which might preserve energy resources in both C. elegans and mammalian adipocytes.26:T439,SREBP1c is a key transcription factor for de novo lipogenesis. Although SREBP1c is expressed in pancreatic islets, its physiological roles in pancreatic β-cells are largely unknown. In this study, we demonstrate that SREBP1c regulates β-cell compensation under metabolic stress. SREBP1c expression level was augmented in pancreatic islets from obese and diabetic animals. In pancreatic β-cells, SREBP1c activation promoted the expression of cell cycle genes and stimulated β-cell proliferation through its novel target gene, PAX4 Compared with SREBP1c^+/+ mice, SREBP1c^-/- mice showed glucose intolerance with low insulin levels. Moreover, β-cells from SREBP1c^-/- mice exhibited reduced capacity to proliferate and secrete insulin. Conversely, transplantation of SREBP1c-overexpressing islets restored insulin levels and relieved hyperglycemia in streptozotocin-induced diabetic animals. Collectively, these data suggest that pancreatic SREBP1c is a key player in mediating β-cell compensatory responses in obesity.

#	Concept	H-Index	Publications	Citations
1	Medicine	3	3	171
2	Natural Sciences	2	2	123
3	Biochemistry	2	2	123
4	Health Sciences	1	1	48
5	Cell Biology	1	1	101

	Year	Citations

About

Top Concepts