Although the mechanisms by which hypothalamic cAMP regulates food intake, physical activity and leptin sensitivity are not know, our study identifies AC3 in the primary cilia of the hypothalamus as a critical 4′-Chloropropiophenone source of cAMP important for regulation of these processes. One of the most striking things about the distribution of AC3 in neurons of the VMH is the fact that it is localized almost exclusively to primary cilia. Although the function of these structures in hypothalamic neurons is not known, it is interesting that there are a number of human diseases and transgenic mice in which alterations in components of the primary cilia are associated with obesity. For example, Bardel-Biedl syndrome is a pleiotropic disorder characterized by a multitude of symptoms, including obesity. BBS is due to disruption of the cilia/basal body. Alstrom syndrome is a rare autosomal recessive disorder characterized by obesity, insulin resistance, and type 2 diabetes. ALSM1 is also thought to be due to a defect in primary cilia. Precise and complex regulation is required for entering a developmental pathway at the correct time and in the appropriate cell type. Deviations from this regulation may lead to genome instability, causing either cell death or the formation of tumor cells. Inducing the correct set of genes in a coordinated manner is a key for developmental pathway regulation and is often achieved through a transcriptional regulatory cascade. The master activator initiating the cascade is usually controlled by multiple input signals, each with a small impact. It is the combinational nature of the induction of the master activator that Palmitic-acid ensures the correct spatial and temporal activity of the developmental pathway. Transmission of a strong and short-lived signal by the master activator is assumed to be critical for the successful completion of a developmental pathway. Studies in mice and yeast meiosis have demonstrated the importance of a short-lived signal for efficient entry into a developmental pathway. However, whether a strong signal is indeed essential for efficient entry into and completion of a developmental pathway and, if not, how cells cope with premature, delayed, reduced, or increased signals, remains a fundamental, unsolved question.