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- Title:
Time-resolved hypothalamic open flow micro-perfusion reveals normal leptin transport across the blood-brain barrier in leptin resistant mice.
- Document type:
- Journal Article; Research Support, Non-U.S. Gov't
- Author(s):
- Kleinert, Maximilian; Kotzbeck, Petra; Altendorfer-Kroath, Thomas; Birngruber, Thomas; Tschöp, Matthias H; Clemmensen, Christoffer
- 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.
- Journal title abbreviation:
- Mol Metab
- Year:
- 2018
- Journal volume:
- 13
- Pages contribution:
- 77-82
- Fulltext / DOI:
- doi:10.1016/j.molmet.2018.04.008
- Pubmed ID:
- http://view.ncbi.nlm.nih.gov/pubmed/29748097
- TUM Institution:
- Lehrstuhl für Stoffwechselerkrankungen (Prof. Tschöp)
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