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Up‐Regulation of Blood‐Brain Barrier Short‐Form Leptin Receptor Gene Products in Rats Fed a High Fat Diet
Author(s) -
Boado Ruben J.,
Golden Pamela L.,
Levin Nancy,
Pardridge William M.
Publication year - 1998
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1046/j.1471-4159.1998.71041761.x
Subject(s) - leptin , leptin receptor , gene isoform , medicine , endocrinology , adipose tissue , receptor , immunocytochemistry , messenger rna , biology , blood–brain barrier , central nervous system , gene , biochemistry , obesity
Leptin is a 16‐kDa protein synthesized in adipose tissue that produces a satiety effect in the CNS. Leptin may gain access to the brain via receptor‐mediated transport through the blood‐brain barrier (BBB), and the BBB leptin receptor (OBR) may regulate the availability of circulating leptin to brain cells. The aim of the present study was twofold: first, to identify the OBR isoform expressed at the BBB, i.e., short, or “a,” and long, or “b,” form; and second, to compare the abundance of the BBB OBR mRNA and protein between control and high fat‐fed rats. RT‐PCR with isoform‐specific primers showed that OBRa is the most abundant isoform at the BBB. BBB OBRa transcript content was markedly increased in high fat‐fed rats compared with controls (11‐fold), and no changes were observed in the expression of the internal standard control actin. The high fat feeding induction of OBR mRNA was correlated with an increase in the immunoreactive BBB OBR determined by immunocytochemistry using an all‐isoform reactive antibody in high fat‐fed obese rats. This investigation demonstrates (a) the OBRa is the principal leptin receptor expressed at the BBB and (b) this BBB OBR isoform is up‐regulated by a high fat diet.