Aims: 

Orexins are peptides involved in autonomic control and thus also in energy homeostasis. Prepro-orexin gene knock out mice display a phenotype towards to obese. We created a transgenic mice line expressing human prepro-orexin (hPPO) under its own promoter in order to investigate its effects on energy homeostasis.

Methods: 

Transgenic mice were characterized using real-time PCR, and mRNA expression of uncoupling proteins (UCP) 1–3 from brown adipose tissue (BAT), white adipose tissue (WAT) and skeletal muscle were analyzed. Metabolic performance, locomotor activity as well as drinking and feeding behavior of mice housed either at room temperature or cold (+4^°C) were measured using an automated monitoring system.

Results: 

The hPPO/orexin-A was expressed in hypothalamus of transgenic mice. Tg mice are slightly lighter than wt mice. At room temperature transgenic mice exhibited an increased metabolic heat production with a significant change in cumulative daytime eating (38% increase) while there was no change on total food consumption, in drinking behavior or total activity. In response to cold exposure, transgenic mice decreased significantly their total locomotor activity compared with wt mice during the first two nights (4305 ± 416.9 and 6256 ± 623.8 counts, respectively). UCP1 or UCP3 expressions did not differ in BAT, WAT or muscle tissue in mice at room temperature or cold. Expression level of UCP2 in WAT was up-regulated 2-fold in transgenic mice housed at room temperature, but not in other tissues or in cold.

Conclusion: 

hPPO transgenic mice demonstrate that orexins affect energy metabolism via a mechanism independent of UCP1-mediated heat production. Supported in part by the Academy of Finland.