*4.8. Statistical Analysis*

Data were analyzed with Sigma Plot (SYSTAT Software Inc., Erkrath, Germany) by two-way analysis of variance (2-Way ANOVA) followed by Tukey test for pairwise multiple comparisons. *p*-values < 0.05 were considered significant, *p-*values between 0.05 and 0.1 (0.05 < *p* < 0.1) were considered to show a tendency towards significance [47]. Data are expressed as means ± SD or means and individual data points for each mouse. Graphs were created using GraphPad Prism (version 4, GraphPad Software, San Diego, CA, USA) and figures were constructed with Photoshop CS6 (Adobe, San José, CA, USA).

### **5. Conclusions**

In conclusion, high sucrose intake induced hyperglycemia and elastic fiber remodeling that resulted in reduced pulmonary elasticity. In contrast, the alveolar epithelium did not show alterations. This might contribute to the hyperglycemia-related decline in lung function observed in patients and could prime the lung for injury and disease. Future studies are needed to shed further light on this correlation between high blood sugar and ECM remodeling. Voluntary activity prevented hyperglycemia and significantly alleviated elastic fiber alterations in HSD-fed mice, indicating that physical exercise is a potent intervention strategy against sugar-induced pulmonary changes.

**Author Contributions:** Conceptualization, C.M. and J.S.; Data curation, J.H.; Formal analysis, J.H. and J.S.; Investigation, J.H., E.L.-R., and J.S.; Methodology, E.L.-R. and J.S.; Project administration, C.M.; Supervision, C.M. and J.S.; Writing – original draft, J.H. and J.S.; Writing – review & editing, E.L.-R. and C.M.

**Funding:** This research was funded by the Hannover Medical School project funding program, Hochschulinterne Leistungsförderung HiLF.

**Acknowledgments:** We thank Melanie Bornemann, Susanne Kuhlmann, and Rita Lichatz (Institute of Functional and Applied Anatomy, MHH) for excellent technical support. We thank Sheila Fryk for the linguistic revision of the manuscript.

**Conflicts of Interest:** The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

#### **Abbreviations**

