Telmisartan prevents diet-induced obesity and preserves leptin transport across the blood-brain barrier in high-fat diet-fed mice

Franziska Schuster, Gianna Huber, Ines Stölting, Emily E. Wing, Kathrin Saar, Norbert Hübner, William A. Banks, Walter Raasch*

*Korrespondierende/r Autor/-in für diese Arbeit

Abstract

Obesity is a global health problem and treatment options are still insufficient. When chronically treated with the angiotensin II receptor blocker telmisartan (TEL), rodents do not develop diet-induced obesity (DIO). However, the underlying mechanism for this is still unclear. Here we investigated whether TEL prevents leptin resistance by enhancing leptin uptake across the blood-brain barrier (BBB). To address this question, we fed C57BL/6 mice a high-fat diet (HFD) and treated them daily with TEL by oral gavage. In addition to broadly characterizing the metabolism of leptin, we determined leptin uptake into the brain by measuring BBB transport of radioactively labeled leptin after long-term and short-term TEL treatment. Additionally, we assessed BBB integrity in response to angiotensin II in vitro and in vivo. We found that HFD markedly increased body weight, energy intake, and leptin concentration but that this effect was abolished under TEL treatment. Furthermore, glucose control and, most importantly, leptin uptake across the BBB were impaired in mice on HFD, but, again, both were preserved under TEL treatment. BBB integrity was not impaired due to angiotensin II or blocking of angiotensin II receptors. However, TEL did not exhibit an acute effect on leptin uptake across the BBB. Our results confirm that TEL prevents DIO and show that TEL preserves leptin transport and thereby prevents leptin resistance. We conclude that the preservation of leptin sensitivity is, however, more a consequence than the cause of TEL preventing body weight gain.

OriginalspracheEnglisch
ZeitschriftPflugers Archiv European Journal of Physiology
Jahrgang470
Ausgabenummer11
Seiten (von - bis)1673-1689
Seitenumfang17
ISSN0031-6768
DOIs
PublikationsstatusVeröffentlicht - 01.11.2018

Strategische Forschungsbereiche und Zentren

  • Forschungsschwerpunkt: Gehirn, Hormone, Verhalten - Center for Brain, Behavior and Metabolism (CBBM)

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