Ketogenic Diet High in Saturated Fat Promotes Colonic Claudin Expression without Changes in Intestinal Permeability to Iohexol in Healthy Mice

• Published in: Nutrients Vol. 16; no. 1; p. 18
• Main Authors: Luiskari, Lotta, Launonen, Hanna, Lindén, Jere, Lehto, Markku, Vapaatalo, Heikki, Salmenkari, Hanne, Korpela, Riitta
• Format: Journal Article
• Language: English
• Published: Switzerland MDPI AG 20-12-2023; MDPI
• Subjects: Animals; Carbohydrates; Colon; Contrast media; Cytokines; Cytoplasm; Diet; dietary fat; Epilepsy; Ethylenediaminetetraacetic acid; Gastrointestinal diseases; Inflammation; Inflammatory bowel disease; intestinal permeability; ketogenic diet; Ketosis; Medical research; Medicine, Experimental; Metabolism; Microbiota; Permeability; Phosphatases; RNA; Saturated fatty acids; Scientific equipment and supplies industry; Small intestine; tight junction proteins; Tumor necrosis factor; Unsaturated fatty acids; Urine; United States; Finland; France; United States > US; tight junction proteins; intestinal permeability; ketogenic diet; dietary fat
• ISSN: 2072-6643; 2072-6643
• DOI: 10.3390/nu16010018

Ketogenic diets (KDs) have been studied in preclinical models of intestinal diseases. However, little is known of how the fat source of these diets influences the intestinal barrier. Herein, we studied the impact of four-week feeding with KD high either in saturated fatty acids (SFA-KD) or polyunsaturated linoleic acid (LA-KD) on paracellular permeability of the intestine to iohexol in healthy male C57BL/6J mice. We investigated jejunal and colonic tight junction protein expression, histological changes, and inflammatory markers (
,
,
, and
), as well as the activity and expression of intestinal alkaline phosphatase (IAP) in feces and jejunal tissue, respectively, and plasma lipopolysaccharide. KDs did not change intestinal permeability to iohexol after two or twenty-six days of feeding regardless of fat quality. SFA-KD, but not LA-KD, upregulated the colonic expression of tight junction proteins claudin-1 and -4, as well as the activity of IAP. Both KDs resulted in increased epithelial vacuolation in jejunum, and this was pronounced in SFA-KD. Jejunal
expression was lower and colonic
expression higher in LA-KD compared to SFA-KD. In colon,
mRNA was increased in LA-KD when compared to controls. Overall, the results suggest that KDs do not influence intestinal permeability to iohexol but elicit changes in colonic tight junction proteins and inflammatory markers in both jejunum and colon. Future research will show whether these changes become of importance upon proinflammatory insults.