Untargeted metabolomic profiles reveal widespread metabolic perturbations and identify candidate biomarkers in aminoaciduric canine hypoaminoacidemic hepatopathy syndrome

被引：1

作者：

Loftus, John P. ^{[1
]}

Rubio, Elena Diaz ^{[2
,3
]}

Yant, Jillian ^{[1
,4
]}

Bichoupan, Allison ^{[1
,5
]}

Zhang, Sheng ^{[2
]}

Miller, Adam J. ^{[1
,6
]}

Center, Sharon A. ^{[1
]}

Ruiz, Maria D. R. ^{[1
]}

Macho, Luis P. ^{[1
,7
]}

机构：

[1] Cornell Univ, Coll Vet Med, Dept Clin Sci, Loftus Lab, Ithaca, NY 14850 USA

[2] Cornell Univ, Prote & Metabol Facil, Ithaca, NY USA

[3] Rutgers Canc Inst New Jersey, New Brunswick, NJ USA

[4] Friendship Hosp Anim, Washington, DC USA

[5] Small Door Vet West Village, New York, NY USA

[6] Cent Hosp Vet Med, North Haven, CT USA

[7] Adv Vet Care Ctr, Davie, FL USA

来源：

AMERICAN JOURNAL OF VETERINARY RESEARCH | 2023年 / 84卷 / 12期

关键词：

metabolomics; liver; amino acids; hepatocutaneous syndrome; canine (dog); SUPERFICIAL NECROLYTIC DERMATITIS; AMINO-ACID; MIGRATORY ERYTHEMA; GLUCAGON; DOGS; RECEPTOR; PYRUVATE; CHOLINE;

D O I：

10.2460/ajvr.23.08.0186

中图分类号：

S85 [动物医学（兽医学）];

学科分类号：

0906 ;

摘要：

OBJECTIVE To identify metabolites and metabolic pathways affected in dogs with aminoaciduric canine hypoaminoacidemic hepatopathy syndrome (ACHES) compared to healthy control (CON) dogs of similar ages and breeds. To improve our understanding of ACHES pathophysiology and identify novel candidate biomarkers associated with ACHES. ANIMALS A prospective case-control study. Privately owned dogs with ACHES (n = 19) and healthy (CON) dogs (n = 9) were recruited between February 18, 2015, and April 18, 2018. METHODS A prospective case-control study. Plasma and urine were collected from ACHES and CON dogs. The Cornell University Proteomics and Metabolomics Core Facility conducted an untargeted metabolomic analysis. RESULTS After controlling for age, sex, and weight, 111 plasma and 207 urine metabolites significantly differed between ACHES and CON dogs. Data reduction and cluster analysis revealed robust segregation between ACHES and CON dogs. Enrichment analysis of significant compounds in plasma or urine identified altered metabolic pathways, including those related to AA metabolism, cellular energetics, and lipid metabolism. Biomarker analysis identified metabolites that best-distinguished ACHES from CON dogs, including pyruvic acid isomer and glycerol-3-phosphate in the plasma and an alanine isomer and choline in the urine. CLINICAL RELEVANCE Our findings provide an in-depth analysis of metabolic perturbations associated with ACHES. Several affected metabolic pathways (eg, lipid metabolism) offer a new understanding of ACHES pathophysiology. Novel candidate biomarkers warrant further evaluation to determine their potential to aid in ACHES diagnosis, prognosis, and treatment monitoring.

引用

页数：13