Abstract:

Objective ·To investigate the changes of adipose tissues in mice after high-fat diet before and during pregnancy and the potential effects on adipose tissues in their offspring. Methods ·C57BL/6J female mice were randomly assigned to the normal diet (CON group, n=12) or the high-fat diet (HFD group, n=12) for 5 weeks. The two groups were further subdivided according to pregnancy: a normal diet non-pregnancy group (CON-UN group), a normal diet pregnancy group (CON-P group), a high-fat diet non-pregnancy group (HFD-UN group), and a high-fat diet pregnancy group (HFD-P group). The original diet was maintained during pregnancy and lactation. White adipose tissues (WAT) and brown adipose tissues (BAT) were collected from visceral and scapula of mice after 5 weeks of feeding or E18.5d. Offspring from both dietary groups were placed on a normal diet after weaning, and their adipose tissues were collected at the 11th week. H-E staining was used to observe the changes of adipocytes. Flow cytometry was employed to detect the proportions of CD4⁺T cells, CD8⁺T cells, total T cells, CD4⁺T/CD8⁺T and NK cells in WAT. RT-PCR was used to assess the expression of IL-6 and IL-1β mRNA in WAT. Results ·After 5 weeks on a high-fat diet, the body weight of female mice in the HFD group was higher than that in the CON group (P<0.05). Both WAT and BAT weights were markedly increased in the HFD groups before and during pregnancy (both P<0.05). In the WAT from HFD-UN and HFD-P groups, the number of cells within the same visual field decreased, the size of adipose cells varied, the proportion of fat droplets increased and the cell volume expanded. The proportion of lipid drop area to total visual field in the HFD-UN group and HFD-P group was compared with the CON-UN group and CON-P group, respectively, and the difference was statistically significant (all P<0.05). BAT in the HFD-UN and HFD-P groups showed a relatively chaotic arrangement and varying adipocyte sizes, although cell volume remained unchanged. The proportions of CD8⁺T cells and total T cells in adipose tissues were elevated in the HFD-UN and HFD-P groups, accompanied by increased mRNA levels of IL-6 and IL-1β, respectively, compared with the CON-UN and CON-P groups, and the differences were statistically significant (all P<0.05). NK cells proportions decreased at reproductive age (HFD-UN group) but increased significantly during pregnancy (HFD-P group), showing a divergent trend. Despite a return to a normal diet after weaning, offspring from the high-fat diet group had significantly higher weight of body, WAT and BAT, compared to those of normal diet (all P<0.05), and the volume of WAT was significantly enlarged. Conclusion ·A high-fat diet can induce the changes of adipocyte structure and immune cell ratio, and elevate inflammation levels in adipose tissues before and during pregnancy, which also impacts the adipose structure in offspring. Adipose tissue may be a new vector mediating the intergenerational transmission of obesity.

Key words: high-fat diet, adipose tissue, pregnancy, intergenerational transmission