Serum Fatty Acids Are Correlated with Inflammatory Cytokines in Ulcerative Colitis.

BACKGROUND AND AIMS: Ulcerative colitis (UC) is associated with increased dietary intake of fat and n-6 polyunsaturated fatty acids (PUFA). Modification of fat metabolism may alter inflammation and disease severity. Our aim was to assess differences in dietary and serum fatty acid levels between control and UC subjects and associations with disease activity and inflammatory cytokines. METHODS: Dietary histories, serum, and colonic tissue samples were prospectively collected from 137 UC subjects and 38 controls. Both histologic injury and the Mayo Disease Activity Index were assessed. Serum and tissue cytokines were measured by Luminex assay. Serum fatty acids were obtained by gas chromatography. RESULTS: UC subjects had increased total fat and oleic acid (OA) intake, but decreased arachidonic acid (AA) intake vs controls. In serum, there was less percent saturated fatty acid (SFA) and AA, with higher monounsaturated fatty acids (MUFA), linoleic acid, OA, eicosapentaenoic acid (EPA), and docosapentaenoic acid (DPA) in UC. Tissue cytokine levels were directly correlated with SFA and inversely correlated with PUFA, EPA, and DPA in UC subjects, but not controls. 5-aminosalicylic acid therapy blunted these associations. CONCLUSIONS: In summary, we found differences in serum fatty acids in UC subjects that correlated with pro-inflammatory tissue cytokines. We propose that fatty acids may affect cytokine production and thus be immunomodulatory in UC.

L-Arginine Availability and Metabolism Is Altered in Ulcerative Colitis.

BACKGROUND: L-arginine (L-Arg) is the substrate for both inducible nitric oxide (NO) synthase (NOS2) and arginase (ARG) enzymes. L-Arg is actively transported into cells by means of cationic amino acid transporter (SLC7) proteins. We have linked L-Arg and arginase 1 activity to epithelial restitution. Our aim was to determine if L-Arg, related amino acids, and metabolic enzymes are altered in ulcerative colitis (UC). METHODS: Serum and colonic tissues were prospectively collected from 38 control subjects and 137 UC patients. Dietary intake, histologic injury, and clinical disease activity were assessed. Amino acid levels were measured by high-performance liquid chromatography. Messenger RNA (mRNA) levels were measured by real-time PCR. Colon tissue samples from 12 Crohn's disease patients were obtained for comparison. RESULTS: Dietary intake of arginine and serum L-Arg levels were not different in UC patients versus control subjects. In active UC, tissue L-Arg was decreased, whereas L-citrulline (L-Cit) and the L-Cit/L-Arg ratio were increased. This pattern was also seen when paired involved (left) versus uninvolved (right) colon tissues in UC were assessed. In active UC, SLC7A2 and ARG1 mRNA levels were decreased, whereas ARG2 and NOS2 were increased. Similar alterations in mRNA expression occurred in tissues from Crohn's disease patients. In involved UC, SLC7A2 and ARG1 mRNA levels were decreased, and NOS2 and ARG2 increased, when compared with uninvolved tissues. CONCLUSIONS: Patients with UC exhibit diminished tissue L-Arg, likely attributable to decreased cellular uptake and increased consumption by NOS2. These findings combined with decreased ARG1 expression indicate a pattern of dysregulated L-Arg availability and metabolism in UC.