Dietary intervention in obese mice protects the offspring from obesity-related inflammation, vascular remodeling, arrest of alveolarization and pulmonary inflamm-aging in a sex-specific manner

Hintergrund Obesity, a global health problem, is associated with chronic lung diseases (CLD). Prior studies from our group showed that maternal obesity increases the risk for early-life obesity with a subacute inflammation, a converging process of obesity and aging (inflamm-aging) that is related to vascular remodeling and emphysema in the offspring later in life. We hypothesize that maternal dietary intervention at the beginning of pregnancy protects in a sex-specific manner against subacute inflammation, premature aging and structural changes of the lung in the offspring.

Methoden We studied offspring of female C57Bl6N with the following dietary regimens: (i) continuous standard diet (SD); (ii) high-fat diet before and during gestation and lactation; offspring received SD after weaning (HFD); (iii) high-fat diet before gestation and switch to SD from the onset of gestation (HFD^int). Theanimals were sacrificed at postnatal day 21 (P21) and P70, and white adipose tissue (WAT) and lung were excised for analyses, including quantitative histomorphometric analysis, immunostaining, and profiling of adipocytokines.

Ergebnisse (1) Male and female HFD offspring exhibited an early-life obesity with adipocyte hypertrophy at P21, whereas HFD^int protected both sexes. Interestingly, serum leptin and gene expression of adipocytokines were only elevated in male HFD, but not in female HFD. However, male HFD^int were protected from overactive WAT and subacute inflammation. (2) Quantitative histomorphometric analyses revealed fewer and larger alveoli in male HFD, but not in male HFD^int at P21 and P70. This lung structural phenotype in the HFD group was attenuated in female offspring; however, HFD^int preserved alveolarization in both sexes. In contrast, vascular muscularization was increased in both female and male HFD, whereas HFD^int offspring of both sexes were completely protected. (3) Finally, female and male HFD^int offspring were protected from reduced number of alveolar epithelial type 2 cells (AT2) and increased DNA damage in AT2 in the HFD group that was observed in comparison to the SD group.

Schlussfolgerung Our data show sex-dependent early-life obesity with inflammatory WAT in male offspring. In contrast, vascular remodeling, arrest of alveolarization, and alveolar DNA damage after maternal obesity is sex independent. Maternal dietary intervention protected from metabolic and lung structural changes as well as activation of aging processes in the lung.