Beating the Clock for a Better Understanding of Metabolism

Timing is everything, even with regard to metabolism. To test a role for the molecular clock in glucose homeostasis, Garrett FitzGerald and colleagues at the University of Pennsylvania recently studied mice with impaired Bmal1 and Clock, the core genes behind circadian rhythm.¹ These genes encode transcription factors known to play an important role in recovering from insulin-induced hypoglycemia. The studies may implicate dysregulated clock functions in metabolic syndrome, a condition believed to affect as many as 47% of the US population. Features of metabolic syndrome include obesity, high triglyceride levels, insulin resistance, and hypertension.

"Ten percent of genes in the transcriptome tend to oscillate in a circadian fashion," says FitzGerald. "The cassettes of genes that oscillate tended to be those involved in glucose metabolism, lipid metabolism, response to vascular injury, and adipocyte maturation." With congruence of those cassettes, he says, " [it] strikes you that these are the functions dysregulated ...