Net release and uptake of xenometabolites across intestinal, hepatic, muscle, and renal tissue beds in healthy conscious pigs.

Autor: Mercer KE; Arkansas Children's Nutrition Center, Little Rock, Arkansas.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas., Ten Have GAM; Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A & M University, College Station, Texas., Pack L; Arkansas Children's Nutrition Center, Little Rock, Arkansas., Lan R; Arkansas Children's Nutrition Center, Little Rock, Arkansas.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas., Deutz NEP; Center for Translational Research in Aging and Longevity, Department of Health and Kinesiology, Texas A & M University, College Station, Texas., Adams SH; Arkansas Children's Nutrition Center, Little Rock, Arkansas.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas., Piccolo BD; Arkansas Children's Nutrition Center, Little Rock, Arkansas.; Department of Pediatrics, University of Arkansas for Medical Sciences, Little Rock, Arkansas.
Jazyk: angličtina
Zdroj: American journal of physiology. Gastrointestinal and liver physiology [Am J Physiol Gastrointest Liver Physiol] 2020 Aug 01; Vol. 319 (2), pp. G133-G141. Date of Electronic Publication: 2020 Jun 15.
DOI: 10.1152/ajpgi.00153.2020
Abstrakt: Xenometabolites from microbial and plant sources are thought to confer beneficial as well as deleterious effects on host physiology. Studies determining absorption and tissue uptake of xenometabolites are limited. We utilized a conscious catheterized pig model to evaluate interorgan flux of annotated known and suspected xenometabolites, derivatives, and bile acids. Female pigs ( n = 12, 2-3 mo old, 25.6 ± 2.2 kg) had surgically implanted catheters across portal-drained viscera (PDV), splanchnic compartment (SPL), liver, kidney, and hindquarter muscle. Overnight-fasted arterial and venous plasma was collected simultaneously in a conscious state and stored at -80°C. Thawed samples were analyzed by liquid chromatography-mass spectrometry. Plasma flow was determined with para-aminohippuric acid dilution technology and used to calculate net organ balance for each metabolite. Significant organ uptake or release was determined if net balance differed from zero. A total of 48 metabolites were identified in plasma, and 31 of these had at least one tissue with a significant net release or uptake. All bile acids, indole-3-acetic acid, indole-3-arylic acid, and hydrocinnamic acid were released from the intestine and taken up by the liver. Indole-3-carboxaldehyde, p-cresol glucuronide, 4-hydroxyphenyllactic acid, dodecanendioic acid, and phenylacetylglycine were also released from the intestines. Liver or kidney uptake was noted for indole-3-acetylglycine, p-cresol glucuronide, atrolactic acid, and dodecanedioic acid. Indole-3-carboxaldehyde, atrolactic acid, and dodecanedioic acids showed net release from skeletal muscle. The results confirm gastrointestinal origins for several known xenometabolites in an in vivo overnight-fasted conscious pig model, whereas nongut net release of other putative xenometabolites suggests a more complex metabolism. NEW & NOTEWORTHY Xenometabolites from microbe origins influence host health and disease, but absorption and tissue uptake of these metabolites remain speculative. Results herein are the first to demonstrate in vivo organ uptake and release of these metabolites. We used a conscious catheterized pig model to confirm gastrointestinal origins for several xenometabolites (e.g., indolic compounds, 4-hydroxyphenyllactic acid, dodecanendioic acid, and phenylacetylgycine). Liver and kidney were major sites for xenometabolite uptake, likely highlighting liver conjugation metabolism and renal excretion.
Databáze: MEDLINE