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Expression of Leptin Receptor Isoforms in Rat Brain Microvessels

Department of Medicine, Division of Endocrinology (C.B., J.K.L., P.M., R.S.A., J.S.F.), and the Department of Neurology (J.K.E.), Beth Israel Deaconess Medical Center, and Program in Neuroscience (J.K.E.), Harvard Medical School, Boston, Massachusetts 02215; and the Medical Service, Endocrine Division, Department of Veterans Affairs Medical Center and Departments of Medicine and Neurology, Oregon Health Sciences University (A.v.B., A.L.M.), Portland, Oregon 97207

Address all correspondence and requests for reprints to: Dr. Jeffrey S. Flier, Division of Endocrinology, Department of Medicine, Beth Israel Deaconess Medical Center, 99 Brookline Avenue, Research North, Boston, Massachusetts 02215. E-mail: jflier{at}bidmc.harvard.edu

Leptin acts on specific brain regions to affect body weight regulation. As leptin is made by white adipose tissue, it is thought that leptin must cross the blood-brain barrier or the blood-cerebrospinal fluid barrier to reach key sites of action within the brain. High expression of a short form leptin receptor has been reported in the choroid plexus. However, whether one or more of the known leptin receptor isoforms is expressed in brain capillaries is unknown. To identify and quantitate leptin receptor isoforms in rat brain microvessels, we applied quantitative RT-PCR to RNA from purified rat brain microvessels in parallel with in situ hybridization. The results show that the amount of short form leptin receptor messenger RNA (mRNA) in brain microvessels is extremely high, exceeding that in choroid plexus. In contrast, low levels of this mRNA were detected in the cerebellum, hypothalamus, and meninges. The long form leptin receptor mRNA is only present at low levels in the microvessels, but surprisingly, its level in cerebellum is 5 times higher than that in the hypothalamus. In situ hybridization experiments confirmed strong expression of short leptin receptors in microvessels, choroid plexus, and leptomeninges. The distribution and type of leptin receptor mRNA isoforms in brain microvessels are consistent with the possibility that receptor-mediated transport of leptin across the blood-brain barrier is mediated by the short leptin receptor isoform.

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