Zn-Fe primary battery-enabled controlled hydrogen release in stomach for improving insulin resistance in obesity-associated type 2 diabetes.
basic_science · Level V
Where this comes from
- Record sourced from PubMed, PMID 38045569.
- Also identified by DOI 10.1016/j.bioactmat.2023.11.003 and PMC identifier 10689207.
- Licence recorded as CC BY-NC-ND.
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Abstract
Chronic systemic inflammation in obesity-associated type 2 diabetes (T2D) is a key inducing factor of insulin resistance (IR). Hydrogen molecule (H<sub>2</sub>) has been proved to be a safe and effective anti-inflammatory agent, but conventional H<sub>2</sub> administration methods cannot provide a high dosage and a long duration of H<sub>2</sub> treatment in IR-related tissues and thus lead to limited therapeutic efficacies. We here propose a new strategy of controlled H<sub>2</sub> release to match the time window of gastric emptying for maximizing the bioavailability and therapeutic outcome of H<sub>2</sub>. This work enhances the hydrolysis rate of Zn by constructing a Zn-Fe primary-battery micro-/nano-structure, and the H<sub>2</sub>-releasing rate is adjusted by tuning the ratio of Zn to Fe. The Zn-Fe micro-/nano-structure is orally administrated once daily to alleviate obesity-associated T2D in a leptin-deficient (<i>ob/ob</i>) mouse model. The H<sub>2</sub> generation time of the Zn-Fe primary-battery micro-/nano-structure with the Fe/Zn ratio of 1:100 in gastric acid is about 3 h, just matching with the time window of gastric emptying in mice. <i>In vivo</i> monitoring results show that H<sub>2</sub> generated by Zn-Fe micro-/nano-structure in stomach can effectively accumulate in major IR-sited tissues including liver, adipose tissue, and skeletal muscle at a high dose for a relatively long time compared to H<sub>2</sub>-rich water drinking. Oral administration of Zn-Fe micro-/nano-structure at 200 mg/kg body weight has realized an efficient IR improvement and remarkably ameliorated systemic inflammation in <i>ob/ob</i> mice. In addition, a high-dose administration of Zn-Fe shows no visible toxicity in mice. This work provides a new strategy to maximize the outcome of hydrogen therapy.