Health

Scientific publication

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

Publication from Health

Kleinert M, Kotzbeck P, Thomas Altendorfer-Kroath, Dr Thomas Birngruber, Tschöp MH, Clemmensen C

Molecular Metabolism , 4/2018

Abstract:

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.

Keywords: Blood–brain barrier; Hypothalamus; Leptin; Leptin resistance; Leptin transport; Obesity

Url: https://www.sciencedirect.com/science/article/pii/S2212877818302230?via%3Dihub