期刊
MOLECULAR METABOLISM
卷 13, 期 -, 页码 77-82出版社
ELSEVIER
DOI: 10.1016/j.molmet.2018.04.008
关键词
Obesity; Hypothalamus; Leptin; Leptin resistance; Blood-brain barrier; Leptin transport
资金
- Danish Council for Independent Research/Medicine [4004-00233]
- Lundbeck Foundation [R238-2016-2859]
- Novo Nordisk Foundation [NNF17OC0026114]
- European Research Council under the European Union [694968]
- Alexander von Humboldt Foundation
- Helmholtz Alliance ICEMED
- Initiative and Networking Fund of the Helmholtz Association
- Helmholtz initiative on Personalized Medicine iMed
- Helmholtz cross-program Metabolic Dysfunction
- Novo Nordisk Foundation
- European Research Council (ERC) [694968] Funding Source: European Research Council (ERC)
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. (C) 2018 The Authors. Published by Elsevier GmbH.
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