High-Fat Diet Increases HMGB1 Expression and Promotes Lung Inflammation in Mice Subjected to Mechanical Ventilation

Abstract

This study aims to evaluate the effects of a high-fat diet and mechanical ventilation on the pulmonary and systemic inflammatory response in C57BL/6 mice. Male C57BL/6 mice were divided into two groups: one received a standard diet, and the other received a high-fat diet. After 10 weeks, the groups were further divided into two groups each: control group (CG), mechanical ventilation group (MVG), diet group (DG), and diet mechanical ventilation group (DMVG). MVG and DMVG underwent mechanical ventilation for 60 minutes. All animals were euthanized for subsequent analysis. Animals receiving a high-fat diet presented higher body mass, adipose index, and greater adipocyte area. In the lung, the expression of HMGB1 was greater in DG and DMVG than in CG and MVG. CCL2 and IL-22 levels in MVG and DMVG were increased compared to those in CG and DG, whereas IL-10 and IL-17 were decreased. Superoxide dismutase activity was higher in MVG and DMVG than in CG. Catalase activity was lower in DG than in CG, and in MV groups, it was lower than that in CG and DG. MV and obesity promote inflammation and pulmonary oxidative stress in adult C57BL/6 mice.

Figure 1

Effects of the hyperlipidic diet on body mass and adipose tissue. (a) Body mass gain over the 10-week experiment. (b) Body adiposity index. (c) Area of adipocytes. (d) Histological section of epididymal adipose tissue stained with hematoxylin and eosin. Bar = 100 μm. For (a), data are expressed as mean ± standard error of the mean (n = 20). (a) represents difference compared to the control group p < 0.05 using two-way ANOVA followed by the Bonferroni posttest. For (b) and (c), (A) and (C) represent a significant difference in relation to CG and MVG. Data are expressed as mean ± standard error of the mean (n = 10). Analysis was performed by one-way ANOVA followed by Tukey's posttest (p < 0.05).

Figure 2

Immunohistochemistry for HMGB1. (a) Ratio between the number of nuclei labeled for HMGB1 antibody and the total number of nuclei. Data are expressed as mean ± standard error of the mean (n = 10). (A) and (C) represent a significant difference in relation to CG and MVG (p < 0.05) using Kruskal-Wallis analysis followed by Dunn's posttest. (b) Histological section of lung parenchyma stained by immunohistochemical technique. Bar = 100 μm. The arrows point to marked nuclei.

Figure 3

Stereological analyses of lung sections. (a) Volume density of alveolar septa. (b) Volume density of alveolar airspace. (c) Histological section of lung parenchyma stained with H&E. Bar = 50 μm.