The previous found that white adipose tissue (WAT) hyperplasia in obese mice was limited by dietary omega-3 polyunsaturated fatty acids (omega-3 PUFA). Here we aim to characterize the underlying mechanism.

An unhealthy lifestyle, including overnutrition, is the main driving force behind the recent pandemic of obesity and associated diseases. Obesity is defined as an excessive accumulation of body fat, namely in the form of white adipose tissue.

This tissue is characterized by extreme plasticity, and fat depot-specific functional and structural heterogeneity. The main function of WAT is to store energy in triglycerides that are located within lipid droplets in adipocytes.

During exercise, fasting, or cold exposure, fatty acids are released and serve as an energy source. Sufficient capacity for WAT expansion is essential to prevent the spillover of fatty acids and lipotoxic damage of insulin signaling in other tissues. Therefore, both are insufficient in WAT as well as hypertrophic WAT can lead to harmful systemic metabolic consequences.

C57BL / 6N mice were fed to a high-fat diet supplemented or not with omega-3 PUFA for one week or eight weeks; mice fed a standard chow diet were also used. In epididymal WAT (eWAT), DNA content was quantified, immunohistochemical analysis was used to reveal the size of adipocytes and macrophage content, and lipidomic analysis and gene expression screen were performed to assess inflammatory status.

The stromal-vascular fraction of eWAT, which contains most of the eWAT cells, except for adipocytes, was characterized using flow cytometry. Omega-3 PUFA supplementation limited the high-fat-diet-induced increase in eWAT weight, cell number (DNA content), inflammation, and adipocyte growth.

eWAT hyperplasia

eWAT hyperplasia was compromised due to the limited increase in the number of preadipocytes and a decrease in the number of endothelial cells. The number of leukocytes and macrophages was unaffected, but a shift in macrophage polarization towards a less effective phenotype was observed.

The results document that the counteraction of eWAT hyperplasia by omega-3 PUFA in dietary-obese mice reflects an effect on the number of adipose lineage and endothelial cells.

The previous results also indicated that, in addition to modulating the immunometabolic properties of WAT, the reduced accumulation of body fat due to omega-3 PUFA supplementation in mice fed a high-fat diet was in part due to a prevention of the increase in tissue cell number