Dietary Fat-Fiber Interactions: Effect on Colonic Mediators of Cell Cytokinetics
In order to elucidate the biochemical mechanisms by which dietary fat and fiber modulate colonic cell proliferation and thus colon carcinogenesis, groups of 10 rats were fed one of 9 diets for 3 weeks: 3 types of fat at 15% by weight (beef tallow, corn oil, and fish oil) × 2 types of fiber (pectin and cellulose) plus fiber-free as a control group. The overall colonic fatty acid composition in mucosal total phospholipids reflected the incorporation of dietary fatty acids. An increase in the level of mucosal phospholipid arachidonic acid (20:4n-6) mass was associated with increased cell proliferation in the distal colon (r = 0.70, p < 0.05), measured by in vivo incorporation of bromodeoxyuridine (BRDU), whereas, an increase in the total phospholipid levels of fish oil derived n-3 fatty acids (20:5n-3 and 22:6n-3) was associated with decreased cell proliferation (r = −0.73, p < 0.05). The synthesis of prostaglandin E2 (PGE2) and PGI2 derived from 20:4n-6, was significantly reduced by fish oil feeding (p < 0.01). In distal mucosa, pectin supplementation significantly increased PGE2 and PGI2 biosynthesis ex vivo (p < 0.05). Interestingly, there was a site-specific relationship between PGI2 synthesis and cell proliferation. PGI2 levels were negatively correlated in the proximal colon (r = −0.67, p = 0.048) and positively correlated in the distal colon (r = 0.65, p = 0.059), implying the effects of PG in the colon may be site specific. The main effect of fiber on cell proliferation was noted in the proximal colon, where pectin stimulated proliferation compared to cellulose and fiber-free diets (p < 0.05). Comparatively, the main effect of fat was confined to the distal colon, where beef tallow was more promotive with respect to cell proliferation compared to fish and corn oil fed animals (p < 0.05). However, in the proximal colon, the effect of fiber was highly dependent on the source of fat in the diet. Therefore, dietary fiber and fat modulate colonic cell proliferation in an interactive-site-specific manner. Since the effect of fiber on mucosal cell proliferation was confined to the proximal colon, protein kinase C (PKC) activity in membrane and cytosolic fractions was determined in proximal colonic mucosa. Protein kinase C activity was modulated by both the type of dietary fat and the source of fiber (p < 0.05). Increased membrane PKC activity (r = 0.76, p = 0.02) and increased PKC membrane/cytosol ratio (r = 0.64, p = 0.06) were positively associated with increased colonic crypt proliferative zone. These data suggest that the effects of dietary fibers and fats on colonic cell proliferation may be mediated in part through the modulation of mucosal PKC activity.