In This Issue of Diabetes

Data in this issue of Diabetes (p. 1981) show differences in the sensitivity of vascular and metabolic tissues to obesity-related loss of diurnal variation. It has been demonstrated in transgenic mouse models that mutation of core clock genes can lead to obesity, and diet-induced obesity (DIO) in wild-type mice has been shown to lead to secondary blunting of rhythmic clock gene transcription in liver and fat tissue. In humans responding to glucose challenge, obesity is associated with blunting of the normal diurnal response. However, no previous studies have looked at the effect of obesity on rhythmic transcription of core clock genes in cardiovascular tissues or upon normal physiological variation in vascular function. Furthermore, the sensitivity of different tissues to clock disruption in disease remains unknown, as does the relationship of insulin resistance and infl ammation to the obesity-related loss of clock rhythm. In a DIO mouse model, Prasai et al. looked at the cycling of clock genes Bmal1 and Per2. They found that cycling was impaired in metabolic tissues but not in cardiovascular tissues. Another series of experiments showed that clock rhythm disruption occurs in conjunction with tissue infl ammation, but not with insulin resistance. Although studying the effect of obesity on clock genes in humans is diffi cult due to the need for repeated invasive tissue sampling, these fi ndings suggest that investigation in humans may be warranted. — Laura Gehl, PhD