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

Molecular Metabolism
Maximilian KleinertChristoffer Clemmensen

Abstract

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. 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. 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. These data suggest that leptin transport across the BBB is not impaired in non-obese leptin resist...Continue Reading

Citations

Apr 9, 2019·The Journal of Endocrinology·María F AndreoliMario Perello
Oct 5, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Luke HarrisonPaul T Pfluger
Nov 14, 2019·Nutrients·Andrea G IzquierdoMarcos C Carreira
Apr 4, 2019·Frontiers in Neuroscience·Sooyeon YooSeth Blackshaw
Nov 6, 2020·Endocrine Reviews·Sandra PereiraTimothy J Kieffer
Feb 13, 2021·Journal of the American College of Cardiology·Nikolaos PerakakisChristos S Mantzoros
Jun 5, 2021·Hormones and Behavior·Jin PengXiaohui Wang

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Methods Mentioned

BETA
ELISA
pharmacotherapy

Software Mentioned

SYSTAT
SigmaPlot
Prism
GraphPad

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