Article ID | Journal | Published Year | Pages | File Type |
---|---|---|---|---|
8536976 | Pharmacology & Therapeutics | 2018 | 65 Pages |
Abstract
Obese and type 2 diabetic (T2DM) patients have a high prevalence of nonalcoholic fatty liver disease (NAFLD). NAFLD is a continuum of chronic liver diseases ranging from benign hepatosteatosis to nonalcoholic steatohepatitis (NASH), cirrhosis and primary hepatocellular cancer (HCC). Because of its strong association with the obesity epidemic, NAFLD is rapidly becoming a major public health concern worldwide. Surprisingly, there are no FDA approved NAFLD therapies; and current therapies focus on the co-morbidities associated with NAFLD, namely, obesity, hyperglycemia, dyslipidemia, and hypertension. The goal of this review is to provide background on the disease process, discuss human studies and preclinical models that have examined treatment options. We also provide an in-depth rationale for the use of dietary Ï3 polyunsaturated fatty acid (Ï3 PUFA) supplements as a treatment option for NAFLD. This focus is based on recent studies indicating that NASH patients and preclinical mouse models of NASH have low levels of hepatic C20-22 Ï3 PUFA. This decline in hepatic PUFA may account for the major phenotypic features associated with NASH, including steatosis, inflammation and fibrosis. Finally, our discussion will address the strengths and limitations of Ï3 PUFA supplements use in NAFLD therapy.
Keywords
ChREBPLDLRMUFAPPARNASCD36FADSMCDFXRNEFAAKT2collagen 1A1ECMmTORCATP citrate lyaseDNLCOL1A1γGTFABPElongaseELOVLACYLMlxNAFLDEPACOXEGFPI3KALAALTMMPACCERK1/2HCCγ-Glutamyl transferaseASTAspartate aminotransferaseAlanine aminotransferasecyclooxygenaseAtglde novo lipogenesisnonalcoholic steatohepatitisacetyl coA carboxylaseα-linolenic acidEicosapentaenoic aciddocosahexaenoic acidFatty acid desaturaseLinoleic acidfatty acid synthasenon-esterified fatty acidsmonounsaturated fatty acidsFatty acid oxidationNonalcoholic fatty liver diseaseARADHAMetabolic syndromeextracellular signal regulated kinasecomparative gene identification-58epidermal growth factorFAOFasnphosphoinositol-3-kinaseadipocyte triglyceride lipaseExtracellular matrixMatrix metalloproteaseMETSNash Fatty acid binding proteinHepatocellular carcinomacholesterol esterslow density lipoprotein receptor
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Authors
Donald B. Jump, Kelli A. Lytle, Christopher M. Depner, Sasmita Tripathy,