Metabolomics reveals that hepatic stearoyl-CoA desaturase 1 downregulation exacerbates inflammation and acute colitis.
To investigate the pathogenic mechanism of ulcerative colitis, a dextran sulfate sodium (DSS)-induced acute colitis model was examined by serum metabolomic analysis. Higher levels of stearoyl lysophosphatidylcholine and lower levels of oleoyl lysophosphatidylcholine in DSS-treated mice compared to controls led to the identification of DSS-elicited inhibition of stearoyl-CoA desaturase 1 (SCD1) expression in liver. This decrease occurred prior to the symptoms of acute colitis and was well correlated with elevated expression of proinflammatory cytokines. Furthermore, Citrobacter rodentium-induced colitis and lipopolysaccharide treatment also suppressed SCD1 expression in liver. Scd1 null mice were more susceptible to DSS treatment than wild-type mice, while oleic acid feeding and in vivo SCD1 rescue with SCD1 adenovirus alleviated the DSS-induced phenotype. This study reveals that inhibition of SCD1-mediated oleic acid biogenesis exacerbates proinflammatory responses to exogenous challenges, suggesting that SCD1 and its related lipid species may serve as potential targets for intervention or treatment of inflammatory diseases.
Chen
Chi
C
Laboratory of Metabolism, Center for Cancer Research, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.
Shah
Yatrik M
YM
Morimura
Keiichirou
K
Krausz
Kristopher W
KW
Miyazaki
Makoto
M
Richardson
Terrilyn A
TA
Morgan
Edward T
ET
Ntambi
James M
JM
Idle
Jeffrey R
JR
Gonzalez
Frank J
FJ
D000818:Animals; D003092:Colitis / Q000209:etiology*; D016264:Dextran Sulfate; D004195:Disease Models, Animal; D015536:Down-Regulation; D007249:Inflammation / Q000209:etiology*; D050356:Lipid Metabolism / Q000502:physiology*; D008099:Liver / Q000378:metabolism*; D051379:Mice; D010713:Phosphatidylcholines / Q000032:analysis; D013230:Stearoyl-CoA Desaturase / Q000037:antagonists & inhibitors* / Q000172:deficiency
D010713:Phosphatidylcholines; D016264:Dextran Sulfate; C490333:Scd1 protein, mouse; D013230:Stearoyl-CoA Desaturase