Highlights From the Latest in Diabetes Research

Adipocytes play multiple roles in energy balance: they store and release energy and also provide signals to the CNS about energy storage. One example of the importance of white adipose tissue in energy balance involves release of fatty acids into the circulation. When this occurs, fatty acid concentrations increase in the hypothalamus—a change that results in signals that decrease food intake. Growing interest in circadian control of the systems underpinning appetite and feeding led to the observation that mice with germline knockout of Arntl (a gene encoding a key molecular clock element) are heavier and have more adipose tissue than their wild-type counterparts and that these differences become evident as early as 4–8 weeks. A new report by Paschos et al. takes this line of investigation further by determining the impact on weight and food intake when Arntl is specifi cally deleted from adipocytes. The investigators demonstrate that in contrast to mice in which Arntl is deleted in hepatocytes of β-cells, loss of Arntl in adipocytes led to marked disruption of circadian oscillation of circulating free fatty acids. Although mice lacking adipocyte Arntl were born with the same weight as their wild-type counterparts, mutant mice were signifi cantly heavier at 9 weeks. This occurs because Arntl regulates the circadian release of polyunsaturated fatty acids, which act on the hypothalamus to regulate feeding behavior. Specifi cally, increased hypothalamic levels of unesterifi ed polyunsaturated free fatty acids, as occurs during the day, inhibit feeding behavior in mice. Thus, absence of Arntl leads to lower circulating and hypothalamic concentrations of polyunsaturated fatty acids during the daytime, leading to increased food intake. Their study also indicated that even in settings where the total number of calories was held constant, mutant mice that were fed a high-fat diet and whose feeding was restricted to the light period gained more weight than their counterparts that were fed during the dark period. The investigators then showed that relative to controls, mice lacking adipocyte Arntl had higher expression of neuropeptide Y and agouti-related peptide (both appetite-inducing) during the light cycle and lower levels of cocaine-and amphetamine-regulated transcript, which would inhibit appetite and increase thermogenesis. Consistent with increased weight, mutant mice also had higher circulating concentrations of triglycerides and saturated fatty acids. In contrast, they had lower circulating concentrations of unsaturated fatty acids, which were associated with lower fatty acid levels in the hypothalamus that may in turn increase …