Time-resolved hypothalamic open flow micro-perfusion reveals normal leptin transport across the blood–brain barrier in leptin resistant mice

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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.

Original languageEnglish
JournalMolecular Metabolism
Volume13
Pages (from-to)77-82
Number of pages6
ISSN2212-8778
DOIs
Publication statusPublished - 2018

Bibliographical note

Corrigendum to “Time-resolved hypothalamic open flow micro-perfusion reveals normal leptin transport across the blood–brain barrier in leptin resistant mice” (Molecular Metabolism (2018) 13 (77–82), (S2212877818302230), (10.1016/j.molmet.2018.04.008))

    Research areas

  • Blood–brain barrier, Hypothalamus, Leptin, Leptin resistance, Leptin transport, Obesity

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