摘要
Alcoholic liver disease(ALD)comprises a spectrum of liver pathology,including steatosis,steatohepatitis,and cirrhosis.Previous work from our group and others suggests that dietary fat,both the amount and composition,plays a pivotal role in ALD development and progression;however,the impact of specific dietary fatty acids on ALD pathogenesis is not fully elucidated.Preclinical rodent models of ALD revealed the deleterious effects of omega-6 polyunsaturated fatty acids(n-6 PUFAs),specifically linoleic acid(LA),and this may be partially attributed to the increased levels of pro-inflammatory oxidized LA metabolites.There is limited understanding regarding the role of omega-3 polyunsaturated fatty acids(n-3 PUFAs,such as alpha-linolenic acid,eicosapentaenoic acid,and docosahexaenoic acid),and bioactive n-3 PUFAderived lipid molecules in ALD.Given that majority of n-6 and n-3 PUFAs-derived metabolites are potent endogenous signaling molecules,knowledge regarding the changes in these lipid mediators may shed new light on the mechanisms contributing to ALD pathogenesis and reveal novel therapeutic targets and biomarkers of this disease.The current review summarizes relevant scientific literature regarding the role of dietary fat,distinct fatty acids,and bioactive fatty acid metabolites in ALD,and highlights recent advances in the field.
基金
supported by National Institutes of Health(NIH)grants R01 AA024102-01A1(I.A.Kirpich),U01AA022489(C.J.McClain),1U01AA021901-01(C.J.McClain),1U01AA021893-01(C.J.McClain),R01AA023681(C.J.McClain)
the Department of Veterans Affairs I01BX000350(C.J.McClain).Research reported in this publication was supported by the National Institute of Environmental Health Sciences of the National Institutes of Health under Award Number T35ES014559(K.H.Zirnheld)
an Institutional Development Award(IDeA)from the National Institute of General Medical Sciences of the National Institutes of Health under grant number P20GM113226(C.J.McClain)
the National Institute on Alcohol Abuse and Alcoholism of the National Institutes of Health under Award Number P50AA024337(C.J.McClain).
