Rhythmic expression of clock genes is attenuated in the perigonadal adipose tissues of obese KK mice and obese, diabetic KK Ay mice, indicating so that obesity and disease state are intri cately linked to the circadian rhythm. To further inves tigate the differences between rodent models and humans and the association between obesity and circadian rhythm in humans, a similar study in lean and morbidly obese individuals could be conducted. Nevertheless, despite the limitations noted, the major finding is that many genes in the peripheral tissues, such as the adipose in both rodents and humans, exhibit rhythmic expression. The circadian output genes are also linked to metabolism in both spe cies and are affected by such stimuli as restricted feeding.

Rodent studies, examining white and brown adipose tis sue, liver and skeletal muscle, also showed the number of genes under circadian regulation ranging from 3% to 26%, suggesting that a large proportion of the transcrip tome is under circadian control. The estimation from the current study is closer to the upper bound of what has been observed in rodents. This could simply reflect the differences in the experimental designs and sta tistical power to detect changes. On the other hand, it could be attributed to the dominant role of the adipose in driving peripheral clocks in overweight individuals. Clocks in peripheral tissues can be entrained by feeding. One can speculate that feeding patterns in humans may play a substantial role in the synchronization of SCN controlled and food entrainable oscillations.

This syn chronization may lead to more Cilengitide efficient energy utilization by adipose and, in turn, may explain the effect of clock related genes, such as Nocturnin, on resistance to diet induced obesity. Understanding cross species simi larities and differences is necessary for a deeper under standing of how circadian rhythm affects physiology on the whole. Conclusion To our knowledge, this is the first genome wide gene expression profiling study of clinical human adipose sam ples. The results offer new insights into the physiology of adipose tissue in relation to the diurnal cycle, underscor ing the importance of diurnal rhythm for basic physiology of the adipose tissue and energy metabolism in the body. It provides a deeper understanding into the connection between diurnal rhythm, energy metabolism, and growth factor signaling.

Consistent with previous reports, the present findings suggest that the genes linked to PER1 led oscillations may be exploited as novel points selleck of interven tion for obesity and other metabolic phenotypes. A thor ough understanding of diurnal effects on energy metabolism and the link to adipose physiology is impor tant for the selection of novel targets for the treatment of obesity.