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Diabetologia

Erschienen in:

04.07.2016 | Article

Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages

verfasst von: Lei Zhang, Yi-Jing Han, Xian Zhang, Xin Wang, Bin Bao, Wei Qu, Jian Liu

Erschienen in: Diabetologia | Ausgabe 10/2016

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Abstract

Aims/hypothesis

Inflammatory polarisation of adipose tissue macrophages (ATMs) plays a critical role in the development of obesity-associated metabolic diseases such as insulin resistance and diabetes. Our previous study indicated that dietary luteolin (LU) could prevent the establishment of insulin resistance in mice fed a high-fat diet (HFD). Here, we further investigated the effects of LU, which is a natural flavonoid, on pre-established insulin resistance and obesity-associated ATM polarisation in mice.

Methods

Five-week-old C57/BL6 mice were fed on a low-fat diet or HFD for 20 weeks, with some mice receiving supplementation with 0.01% LU from weeks 1 or 10 of the HFD to assess the actions of LU on insulin resistance and ATM polarisation. Furthermore, the role of LU in metabolic-dysfunction-associated macrophage phenotypes was investigated in vitro.

Results

Dietary LU supplementation, either for 20 weeks or from weeks 10 to 20 of an HFD, significantly improved insulin resistance in HFD-fed mice. In addition, inflammatory macrophage infiltration and polarisation were suppressed in mouse epididymal adipose tissues. Furthermore, LU treatment directly reversed lipopolysaccharide-stimulated and metabolism-regulated molecules, and induced inflammatory polarisation in mouse RAW264.7 cells and peritoneal cavity resident macrophages. Finally, using the selective AMP-activated protein kinase (AMPK) inhibitor compound C and Ampkα1 (also known as Prkaa1) silencing with siRNA, we found that LU activated AMPKα1 in macrophages to inhibit their inflammatory polarisation and enhanced insulin signals in adipocytes that were stimulated with macrophage-conditioned media.

Conclusions/interpretation

Dietary LU ameliorated insulin resistance in diet-induced obese mice by promoting AMPKα1 signalling in ATMs.

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Titel: Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages
verfasst von: Lei Zhang
Yi-Jing Han
Xian Zhang
Xin Wang
Bin Bao
Wei Qu
Jian Liu
Publikationsdatum: 04.07.2016
Verlag: Springer Berlin Heidelberg
Erschienen in: Diabetologia / Ausgabe 10/2016
Print ISSN: 0012-186X
Elektronische ISSN: 1432-0428
DOI: https://doi.org/10.1007/s00125-016-4039-8

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Luteolin reduces obesity-associated insulin resistance in mice by activating AMPKα1 signalling in adipose tissue macrophages

Abstract

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Live-Webinar: Aktuelle Leitlinien bei Herz-Kreislauf-Erkrankungen

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Abstract

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Methods

Results

Conclusions/interpretation

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