Inhibition of TPN-associated intestinal mucosal atrophy with monoacetoacetin

Total parenteral nutrition (TPN) is associated with intestinal mucosal atrophy. Acetoacetate is oxidized in preference to glucose by both enterocytes and colonocytes and is not present in TPN. The purpose of this study was to determine whether replacement of a portion of glucose calories with monoacetoacetin, the glycerol ester of acetoacetate, could inhibit TPN-associated intestinal atrophy. Male Sprague-Dawley rats (200-250 g) underwent superior vena caval cannulation and were assigned to receive chow ad libitium (CHOW), TPN with 0.86 M monoacetoacetin (ACAC), or TPN with 0.86 M glycerol to control for the glycerol component of monoacetoacetin (GLYC). Nitrogen balance was measured over 7 days after which time the animals were weighed and sacrificed. Jejunal and colonic segments were harvested and the mucosal weight, protein, RNA, and DNA contents measured. All groups showed comparable weight gain. Cumulative nitrogen balance was positive for both TPN groups. Significant decreases in mucosal parameters occurred in both TPN groups compared to the CHOW group, but atrophy was significantly inhibited in both jejunum and colon of the ACAC group compared to the GLYC group. Thus, the substitution of monoacetoacetin for glucose calories in parenteral nutrition solutions inhibited TPN-related atrophy of intestinal mucosa while maintaining normal growth.