Abstract
The biological properties of polyunsaturated fatty acid (PUFA) classes have been the source of much contention. For example, nβ3 PUFA are chemoprotective, whereas nβ6 PUFA may promote tumor development. Since dietary components can have combinatorial effects, we further examined the apoptotic properties of nβ3 or nβ6 fatty acids when combined with different fiber sources. Mice were fed diets supplemented with either fish oil (FO; enriched in nβ3 PUFA) or corn oil (CO; enriched in nβ6 PUFA) and nonfermentable (cellulose) or fermentable (pectin) fiber sources. In complementary experiments, immortalized young adult mouse colonic (YAMC) cells were treated with docosahexaenoic acid (DHA; 22:6__n__β3) or linoleic acid (LA; 18:2__n__β6) with or without butyrate. Mice fed a FO and pectin diet had significantly (p < 0.05) increased levels of apoptosis in colonocytes compared to all other diets. Similarly, apoptosis was highly induced in DHA and butyrate cotreated YAMC cells. In contrast, in both YAMC and mouse models, LA/CO with butyrate/pectin treatment reduced apoptosis and enhanced expression of bclβ2. The LA and butyrate induced antiapoptotic phenotype was reversed by knocking down bclβ2 using targeted siRNA. In comparison, overexpression of bclβ2 blocked the proapoptotic effect of DHA and butyrate. These data provide new mechanistic insights into the regulation of apoptosis by dietary PUFA and fiber.