Dietary Omega-3 Fatty Acids Prevented Adipocyte Hypertrophy by Downregulating DGAT-2 and FABP-4 in a Sex-Dependent Fashion

Obesity is characterized by an increase in fat mass primarily as a result of adipocyte hypertrophy. Diets enriched in omega (n)‐3 polyunsaturated fatty acids (PUFA) are suggested to reduce obesity, however, the mechanisms are not well understood. We investigated the effect of n‐3 PUFA on adipocyte hypertrophy and the key genes involved in adipocyte hypertrophy. Female C57BL/6 mice were fed semi‐purified diets (20 % w/w fat) containing high n‐3 PUFA before mating, during pregnancy, and until weaning. Male and female offspring were continued on high n‐3 PUFA (10 % w/w), medium n‐3 PUFA (4 % w/w), or low n‐3 PUFA (2 % w/w) diet for 16 weeks postweaning. Adipocyte area was quantified using microscopy, and gonadal mRNA expression of acyl CoA:diacylglycerol acyltransferase‐2 (DGAT‐2), fatty acid binding protein‐4 (FABP‐4) and leptin were measured. The high n‐3 PUFA group showed higher levels of total n‐3 PUFA in gonadal TAG compared to the medium and low n‐3 PUFA groups (P < 0.001). The high n‐3 PUFA male group had a lower adipocyte area compared to the medium and low n‐3 PUFA group (P < 0.001); however, no difference was observed in females. The high n‐3 PUFA male group showed lower mRNA expression of FABP‐4, DGAT‐2 and leptin compared to the low n‐3 PUFA group, with no difference in females. Plasma lipid levels were lower in the high n‐3 PUFA group compared to the other groups. Our findings show for the first time that n‐3 PUFA prevents adipocyte hypertrophy by downregulating FABP‐4, DGAT‐2 and leptin; the effects are however sex‐specific.