Time-resolved hypothalamic open flow micro-perfusion reveals normal leptin transport across the blood–brain barrier in leptin resistant mice
Publikation: Bidrag til tidsskrift › Letter › Forskning › fagfællebedømt
Dokumenter
- Kleinert et al_Molecular Metabolism_2018_Vol 13_77-82_(Short communication)
Forlagets udgivne version, 733 KB, PDF-dokument
Objective: The inability of leptin to suppress food intake in diet-induced obesity, sometimes referred to as leptin resistance, is associated with several distinct pathological hallmarks. One prevailing theory is that impaired transport of leptin across the blood–brain barrier (BBB) represents a molecular mechanism that triggers this phenomenon. Recent evidence, however, has challenged this notion, suggesting that leptin BBB transport is acquired during leptin resistance.
Methods: To resolve this debate, we utilized a novel cerebral Open Flow Microperfusion (cOFM) method to examine leptin BBB transport in male C57BL/6J mice, fed a chow diet or high fat diet (HFD) for 20 days.
Results: Basal plasma leptin levels were 3.8-fold higher in HFD-fed mice (p < 0.05). Leptin administration (2.5 mg/kg) elicited similar pharmacokinetic profiles of circulating leptin. However, while leptin reduced food intake by 20% over 22 h in chow-fed mice, it did not affect food intake in HFD-fed mice. In spite of this striking functional difference, hypothalamic leptin levels, as measured by cOFM, did not differ between chow-fed mice and HFD-fed mice following leptin administration.
Conclusions: These data suggest that leptin transport across the BBB is not impaired in non-obese leptin resistant mice and thus unlikely to play a direct role in the progression of pharmacological leptin resistance.
Originalsprog | Engelsk |
---|---|
Tidsskrift | Molecular Metabolism |
Vol/bind | 13 |
Sider (fra-til) | 77-82 |
Antal sider | 6 |
ISSN | 2212-8778 |
DOI | |
Status | Udgivet - 2018 |
Bibliografisk note
CURIS 2018 NEXS 203
Antal downloads er baseret på statistik fra Google Scholar og www.ku.dk
ID: 197769180