Journal
DIABETOLOGIA
Volume 59, Issue 10, Pages 2219-2228Publisher
SPRINGER
DOI: 10.1007/s00125-016-4039-8
Keywords
Adipose tissue macrophage; AMPK alpha 1; Insulin resistance; Luteolin; Polarisation
Categories
Funding
- National Natural Science Foundation of China [31171315]
- Fundamental Research Funds for Central Universities, China [2014HGCH0005]
- Anhui Science and Technology Research Projects of China [1401b042018]
- Anhui Provincial Natural Science Foundation of China [1408085QC48, 1508085MC58]
Ask authors/readers for more resources
Aim/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 Ampk alpha 1 (also known as Prkaa1) silencing with siRNA, we found that LU activated AMPK alpha 1 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 AMPK alpha 1 signalling in ATMs.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available