Type 2 diabetes mellitus (T2DM) characterized by insulin resistance has become a serious health threat. Chronic inflammation is believed to play a pivotal role in the development of T2DM. Previous study has shown that HO-1 plays an anti-inflammatory role, suggesting HO-1 inhibition could be an effective strategy to treat T2DM. However, application of HO-1 inhibitors is restricted due to their low solubility. In this study, we detected the role of HO-1 inhibitor, ZnPP, in regulating glucose homeostasis and inflammation during obesity. We encapsulated ZnPP with nanoparticles to increase its water solubility and delivered ZnPP-laden nanoparticles (Nano-ZnPP) to the obese mice. We found that inhibition of HO-1 by Nano-ZnPP significantly decreases adiposity, increases insulin resistance, and improves glucose tolerance in diet-induced obesity mice. Moreover, Nano-ZnPP treatment attenuated both local and systematical inflammatory levels during obesity. Mechanistically, Nano-ZnPP significantly attenuated glucagon, TNF, and fatty acid synthesis signaling pathway in liver. In white adipose tissue, oxidative phosphorylation signaling pathway was enhanced and inflammation signaling pathway was diminished by Nano-ZnPP. Our results showed that Nano-ZnPP has a better effect on improving glucose homeostasis and attenuating chronic inflammation, as compared to DMSO-dissolved ZnPP. These results indicate that ZnPP-laden nanoparticles could be a potential therapeutic agent to treat T2DM.


W.Yang: None. Y.Sun: None. S.Guo: None. M.Arora: None. H.Han: None. W.Jiang: None. D.Kim: None. W.Ai: None. Q.Pan: None. M.Kumar: None. W.Brashear: None.


National Institutes of Health (R01DK095118, R01DK120968, R01DK118334, R01AG064869)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at http://www.diabetesjournals.org/content/license.