Increase in long-chain polyunsaturated fatty acid n−6/n−3 ratio in relation to hepatic steatosis in patients with non-alcoholic fatty liver disease

Abstract

Hepatic steatosis is a major feature associated with NAFLD (non-alcoholic fatty liver disease). The aims of the present study were to assess the levels of PUFA (polyunsaturated fatty acids) in liver total lipids, triacylglycerols (triglycerides) and phospholipids of NAFLD patients in relation to those in adipose tissue and hepatic indexes related to oxidative stress as factors contributing to hepatic steatosis. Eleven control subjects and 19 patients with NAFLD were studied. Analysis of liver and abdominal adipose tissue fatty acids was carried out by GLC. The liver content of protein carbonyl groups and malondialdehyde were taken as indexes related to oxidative stress. NAFLD patients had a depletion in LCPUFA (long-chain PUFA) of the n -6 and n -3 series in liver triacylglycerols, with decreased 20:4, n -6/18:2, n -6 and (20:5, n -3+22:6, n -3)/18:3, n -3 ratios, whereas liver phospholipids contained higher n -6 and lower n -3 LCPUFA. These findings were accompanied by an enhancement of (i) n -6/ n -3 ratio in liver and adipose tissue, (ii) 18:1, n -9 trans levels in adipose tissue, and (iii) hepatic lipid peroxidation and protein oxidation indexes. It is concluded that a marked enhancement in LCPUFA n -6/ n -3 ratio occurs in the liver of NAFLD patients, a condition that may favour lipid synthesis over oxidation and secretion, thereby leading to steatosis. Depletion of hepatic LCPUFA may result from both defective desaturation of PUFA, due to inadequate intake of precursors, such as 18:3, n -3, and higher intake of the 18:1, n -9 trans isomer leading to desaturase inhibition, and from an increased peroxidation of LCPUFA due to oxidative stress.

Up-regulated HOTAIR induced by fatty acids inhibits PTEN expression and increases triglycerides accumulation in HepG2 cells

“…The present study used FFAs to establish a cell model of human NAFLD. The results showed triglyceride accumulation in HepG2 cells after treatment with FFAs, consistent with previous studies [27][28][29][30].…”

“…When obesity causes triglycerides failure to be stored in the adipose tissue, triglycerides are transformed into FFAs that are transported to nonadipose tissues [26]. Saturated palmitic (PA; C16:0) and monounsaturated oleic (OA; C18:1) acids are the most abundant FFAs in the liver triglycerides of patients with NAFLD [27,28]. Previous studies showed that in vitro NAFLD models induced by FFAs mixture (PA/OA, 1:2 ratio) could lead to triglyceride accumulation in hepatocytes similar to that of patients with NAFLD, with minor toxic and apoptotic effects [29,30].…”

Prevention of reperfusion injury and microcirculatory failure in macrosteatotic mouse liver by omega‐3 fatty acids†‡

“…This is associated with changes in gene expression, with decreased fatty acid oxidation and triacylglycerol export, and enhanced lipid synthesis, leading to fat accumulation in the liver. 19,27 We believe that macrosteatosis (as a feature of non-alcoholic fatty liver disease) results, at least partially, from abnormal hepatic lipid metabolism caused by imbalanced dietary PUFAs. Inadequate dietary intake of ␣-linolenic compared with lenoleic acid (the parent n-3 and n-6 PUFAs, respectively) leads to defective elongation and desaturation of ␣-linolenic acid because both compete for the enzymes responsible for their elongation and desaturation, leading to decreased production of ␣-linolenic acid long-chain derivatives (EPA and docosapentaenoic acid).…”

Taurine Attenuates Hepatic and Cardiac Damage and Apoptosis in Rabbits Fed a High-Fat Diet

“…The current study was designed to assess the possible protective role of taurine against hypercholesterolemia-induced hepatic and cardic changes by histological and immunohistochemical studies. Ingestion of high-fat diet may lead to fatty acid accumulation and hepatic cell damage and inflammation (Araya et al, 2004). High fat diet have effects on cell death and steatosis (Mei et al, 2011).…”