Orexins are hypothalamic neuropeptides involved in feeding, energy homeostasis and vigilance. They have also been shown to play important role in the periphery. Recently, orexin-A has been reported to affect thermogenesis. Since the peripheral actions of orexins are still unclear, we developed a transgenic (tg) mouse line overexpressing the human prepro-orexin (hPPO) gene under the control of endogenous promoter. Transgenic mice were characterized using PCR, Southern and Western blotting. Metabolic performance, home cage activity as well as drinking and feeding behavior of 6 tg and 6 syngenic (sg) mice were measured using an automated monitoring system. Total RNA was extracted from white and brown adipose tissue (WAT/BAT) and skeletal muscle from fed mice and reverse transcribed to cDNA. Expression of uncoupling proteins (UCP) 1–3 and peroxisome proliferator-activated receptors (PPARs delta and gamma) were analyzed by quantitative real- time PCR. Our tg animals showed significantly increased expression of hPPO/orexin-A. Interestingly, orexin-A was expressed also in WAT indicating a role of orexins as an adipokine. Preliminary evaluation documented a similar food/drink intake and locomotor activity between our animals. However, we found a significant effect on heat production in tg animals. Expression levels of PPARs and UCP2 in WAT were significantly increased in tg mice compared to sg littermates. In conclusions, orexins can regulate heat production and mRNA expression of PPARs as well as UCP2 in WAT thus providing new insights for regulation of body homeostasis.