Alpha-linolenic acid and dietary protein minimally but differentially regulate white adipose tissue lipolysis in female mice fed moderate-fat diets

Omega-3 polyunsaturated fatty acids (n-3 PUFA) influence white adipose tissue (WAT) lipid buffering capacity; however, sex-specific regulation remains understudied. We recently reported that male mice fed a diet containing high alpha-linolenic acid (ALA) had increased WAT mass, reduced serum triglycerides and elevated lipolysis compared to mice fed a diet containing recommended levels of ALA, independent of background dietary protein. The current study examined whether subcutaneous and visceral WAT (scWAT, vWAT) lipolytic activity was altered in female C57BL/6N mice (n=16/group) fed low-ALA (1% energy) or high-ALA (3% energy) diets containing skim milk protein (SMP) or soy protein isolate (SPI) for 8 weeks. Body weight, WAT depot weights and serum triglycerides were unchanged in response to ALA content. Lipolytic markers were mostly unchanged by ALA content except for an increase in adipose triglyceride lipase (ATGL) in vWAT, while diets containing SPI modestly reduced serum cholesterol levels and increased total hormone-sensitive lipase (HSL) content in vWAT. Collectively, WAT lipolytic markers in female mice showed minimal response to diets containing high ALA content, unlike that previously reported in male mice. These results highlight the importance of considering both sexes to ensure generalizability of findings when investigating diet regulation of WAT lipid metabolism.