Fatty liver: Role of inflammation and fatty acid nutrition

Abstract 

Nonalcoholic fatty liver disease (NAFLD) refers to a wide spectrum of liver damage, ranging from simple steatosis to nonalcoholic steatohepatitis (NASH), advanced fibrosis, and cirrhosis. NAFLD is strongly associated with insulin resistance and is defined by accumulation of liver fat >5% per liver weight in the presence of <10g of daily alcohol consumption. The exact prevalence of NAFLD is uncertain because of the absence of simple noninvasive diagnostic tests to facilitate an estimate of prevalence but in subgroups of people such as those with type 2 diabetes, the prevalence may be as high as 70%. NASH is an important subgroup within the spectrum of NAFLD that progresses over time with worsening fibrosis and cirrhosis, and NASH is associated with increased risk for cardiovascular disease. It is, therefore, important to understand the pathogenesis of NASH specifically, to develop strategies for interventions to treat this condition. The purpose of this review is to discuss the roles of inflammation, fatty acids and fatty acids in nutrition, in the pathogenesis and potential treatment of NAFLD.

Abbreviations: NEFA, nonesterified fatty acid, HSL, hormone sensitive lipase, LPL, lipoprotein lipase, VLDL, very-low density lipoprotein, n-3 PUFA, omega – 3 polyunsaturated fatty acid, SREBP-1c, sterol regulatory element binding protein–1c, ACC, acetyl CoA carboxylase, FAS, fatty acid synthentase, mGAT, mitochondrial glycerol 3 phosphate acyltransferase, aGPAT, acylglycerol-sn-3-phosphate acyltransferase, PAP, phosphatidic acid phosphatase, DGAT2, diacyl glycerol acyltransferase–2, CCT–CTP, phosphocholine cytidylyltransferase, CPT–CDP-choline, 1,2 diacylglycerol choline phosphotransferase, PEMT, phosphatidylethanolamine N-methyltransferase, ChREBP, carbohydrate response element binding protein, LXR, liver X receptor, SCD-1, stearoyl CoA desaturase–1, CPT-1, carnitine palmitoyl transferase–1, UCP-2, uncoupling protein – 2, NADPH, nicotinamide adenine dinucleotide phosphate (reduced form)