Differential expression of mRNA for leptin receptor isoforms in the rat brain.

Leptin plays an important role in the control of food intake and energy metabolism by interacting with its receptor (OB-R) in the brain. Several alternatively spliced isoforms of OB-R have been identified. To study the expression patterns and the potential biological function of these OB-Rs in the brain, the distribution of mRNA encoding OB-R isoforms was examined by in situ hybridization. In agreement with previous studies, strong signals for OB-R mRNA were detected in the hypothalamus, thalamus and choroid plexus. In addition, intense signals were observed in several other brain areas including piriform cortex, granule cell layer of the cerebellum and substantia nigra. With isoform-specific probes, a differential expression pattern of OB-Rs was revealed: OB-Ra and OB-Rb, but not OB-Rc and OB-Rf, are abundantly expressed in the hypothalamus, whereas OB-Ra, OB-Rc and OB-Rf, but not OB-Rb, are significantly expressed in the choroid plexus. The preferential expression of OB-Rb in the hypothalamus is in support of its role in mediating the satiety effect of leptin. The co-expression of OB-Ra with OB-Rb in the hypothalamus may suggest a possible interaction between the two isoforms. Finally, the detection of OB-R mRNA in a number of other brain regions may indicate the involvement of leptin in additional as yet undefined physiological functions.