ZnPP-laden nanoparticles improve glucose homeostasis and chronic inflammation during obesity

Wanbao Yang; Meenakshi Arora; Hye Won Han; Wen Jiang; Da Mi Kim; Weiqi Ai; Quan Pan; M N V Ravi Kumar; Wesley A Brashear; Yuxiang Sun; Shaodong Guo

doi:10.1111/bph.16356

ZnPP-laden nanoparticles improve glucose homeostasis and chronic inflammation during obesity

Br J Pharmacol. 2024 Apr 28. doi: 10.1111/bph.16356. Online ahead of print.

Authors

Wanbao Yang¹, Meenakshi Arora^{2

3}, Hye Won Han¹, Wen Jiang¹, Da Mi Kim¹, Weiqi Ai¹, Quan Pan¹, M N V Ravi Kumar^{2

3}, Wesley A Brashear⁴, Yuxiang Sun¹, Shaodong Guo¹

Affiliations

¹ Department of Nutrition, College of Agriculture and Life Sciences, Texas A&M University, College Station, Texas, USA.
² College of Community Health Sciences, The University of Alabama, Tuscaloosa, Alabama, USA.
³ The Center for Convergent Bioscience and Medicine (CCBM), The University of Alabama, Tuscaloosa, Alabama, USA.
⁴ High Performance Research Computing, Texas A&M University, College Station, Texas, USA.

PMID: 38679457
DOI: 10.1111/bph.16356

Abstract

Background and purpose: Chronic inflammation plays a pivotal role in the development of Type 2 diabetes mellitus (T2DM). Previous studies have shown that haem oxygenase-1 (HO-1) plays a proinflammatory role during metabolic stress, suggesting that HO-1 inhibition could be an effective strategy to treat T2DM. However, the application of HO-1 inhibitors is restricted due to solubility-limited bioavailability. In this study, we encapsulated the HO-1 inhibitor, zinc protoporphyrin IX (ZnPP), within nanoparticles and investigated their role in regulating glucose homeostasis and chronic inflammation during obesity.

Experimental approach: We delivered DMSO-dissolved ZnPP (DMSO-ZnPP) and ZnPP-laden nanoparticles (Nano-ZnPP) to diet-induced obese male mice for 6 weeks. Glucose and insulin tolerance tests were carried out, liver and adipose tissue gene expression profiles analysed, and systemic inflammation analysed using flow cytometry.

Key results: Nanoparticles significantly increased the delivery efficiency of ZnPP in both cells and mice. In mice with diet-induced obesity, inhibition of HO-1 by Nano-ZnPP significantly decreased adiposity, increased insulin sensitivity, and improved glucose tolerance. Moreover, Nano-ZnPP treatment attenuated both local and systemic inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signalling pathways in the liver. In white adipose tissue, the oxidative phosphorylation signalling pathway was enhanced and the inflammation signalling pathway diminished by Nano-ZnPP. Our results show that Nano-ZnPP has better effects on the improvement of glucose homeostasis and attenuation of chronic inflammation, than those of DMSO-dissolved ZnPP.

Conclusions and implications: These findings indicate that ZnPP-laden nanoparticles are potential therapeutic agents for treating T2DM.

Keywords: HO‐1; ZnPP; inflammation; nanoparticle; type 2 diabetes.

Abstract

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