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Developmental increases in plasma leptin binding activity and tissue Ob-Re mRNA expression in the rat
Jeremy T Smith1, Peter J Mark, Brendan J Waddell
1School of Anatomy and Human Biology, The University of Western Australia, 35 Stirling Hwy Crawley, Perth, Western Australia 6009, Australia.
The Journal of Endocrinology
|March 8, 2005
Summary
Plasma leptin binding activity, influenced by the leptin receptor isoform Ob-Re, increases significantly from fetal to adult life in rats. This developmental change, particularly in males, impacts leptin
Area of Science:
- Endocrinology
- Molecular Biology
- Developmental Biology
Background:
- Leptin's metabolic and endocrine functions are primarily mediated by its long receptor isoform, Ob-Rb.
- Truncated leptin receptor isoforms, including Ob-Re, influence leptin access to Ob-Rb and contribute to plasma leptin binding activity.
- Ob-Re in circulation can restrict leptin's passage into extravascular tissues, affecting its bioavailability.
Purpose of the Study:
- To investigate developmental changes in plasma leptin binding activity in male and female rats from fetal to adult stages.
- To examine the developmental changes in tissue expression of the leptin receptor isoform Ob-Re mRNA.
- To understand how these changes influence leptin's physiological actions and potential resistance.
Main Methods:
- Measurement of plasma leptin binding activity across different developmental stages (fetal, prepubertal, postpubertal, adult).
- Quantification of Ob-Re messenger RNA (mRNA) expression in various tissues using quantitative reverse transcription polymerase chain reaction (RT-PCR).
- Assessment of hypothalamic Ob-Rb protein content in female rats during development.
Main Results:
- Plasma leptin binding activity was low in fetal and prepubertal rats, increasing significantly post-puberty in males.
- A more modest increase in females led to a noticeable sex difference in binding activity after puberty.
- Ob-Re mRNA was detected in multiple tissues, with a dramatic age-related increase observed in the spleen (>300-fold).
Conclusions:
- Plasma leptin binding activity substantially increases during rat development, influenced by Ob-Re expression.
- Changes in hypothalamic Ob-Rb protein in aging females, coupled with increased plasma binding, suggest a shift towards leptin resistance.
- Leptin's action is regulated not only by its synthesis and receptor expression but also by factors controlling Ob-Re and plasma leptin transport.