A lipidomic analysis of nonalcoholic fatty liver disease

Abstract

The spectrum of nonalcoholic fatty liver disease (NAFLD) includes a nonalcoholic fatty liver (NAFL) and nonalcoholic steatohepatitis (NASH). The specific types and amounts of lipids that accumulate in NAFLD are not fully defined. The free fatty acid (FFA), diacylglycerol (DAG), triacylglycerol (TAG), free cholesterol (FC), cholesterol ester, and phospholipid contents in normal livers were quantified and compared to those of NAFL and NASH, and the distribution of fatty acids within these classes was compared across these groups. Hepatic lipids were quantified by capillary gas chromatography. N onalcoholic fatty liver disease (NAFLD) is a common cause of chronic liver disease in North America. 1 NAFLD is associated with insulin resistance and the metabolic syndrome. 2,3 The clinical-histologic spectrum of NAFLD extends from a nonalcoholic fatty liver (NAFL) to nonalcoholic steatohepatitis (NASH). 4 Although NASH is distinguished from NAFL by the presence of cytologic ballooning and inflammation, both conditions are characterized by a fatty liver. 4,5 Thus, hepatic fat accumulation is the hallmark of NAFLD.The compositions of the lipids that accumulate in the livers of subjects with NAFLD are not well characterized. Most of the published literature has focused on triglyceride accumulation as the key defect in NAFLD. 6,7 However, it is not known whether there are substantial changes in other lipid classes, such as cholesterol and specific phospholipids (PLs). Although an increase in the n-6:n-3 fatty acid ratio in total lipids in NAFLD has been described recently, 8,9 the distribution of these fatty acids within specific lipid classes has not been extensively characterized. Given the important biological activities of many lipids, such information could provide potential insights into the pathophysiology of NAFLD and the metabolic syndrome.A lipidomic approach was taken to quantify the major lipid classes and the distribution of fatty acids within these classes in the liver. The specific aims of the study were to (1) quantify the absolute and relative amounts of free fatty acids (FFAs), diacylglycerol (DAG), triacylglycerol

Desmosterol in Human Nonalcoholic Steatohepatitis

“…To investigate potential mechanisms between serum desmosterol and NASH, we measured total cholesterol and desmosterol in liver tissue as well (available from 62 subjects not differing from the total study group in age, gender distribution, and BMI, Supporting Table 4). As expected, [20][21][22] liver cholesterol correlated with steatosis (r ¼ 0.353, P ¼ 0.005), inflammation (r ¼ 0.421, P ¼ 0.001), and NAFLD activity score (r ¼ 0.378, P ¼ 0.002). The correlation of liver desmosterol with steatosis and inflammation was also significant, but of smaller magnitude ( Table 2).…”

“…16 In NAFLD, liver steatosis is associated with increased cholesterol synthesis and decreased cholesterol absorption. 17 Interestingly, triglyceride accumulation alone may not induce liver injury or inflammation, 18,19 whereas the accumulation of free cholesterol [20][21][22] and the dysregulation of the cholesterol synthesis pathway 23 relates to NASH.…”

Liver and plasma lipid changes induced by cyclic fatty acid monomers from heated vegetable oil in the rat

“…These latter results suggest that lipid accumulation in the liver might not resulted from disturbances in carbohydrate homeostasis (Adeli et al, 2001), due likely to the normal physiological state of rats used in this study. Increased hepatic lipid content is rarely associated with increased cholesterol or phospholipid content, but more often with increased liver TAG (Puri et al., 2007). In this study, only an increase in TAG contributed to the increase in total hepatic fat in the CFAM groups.…”

“…Hepatic PC content is required both for the assembly and secretion of very low‐density lipoprotein (VLDL) and chylomicrons (Skipski et al., 1967). Therefore, as shown in mice, PC protects against the development of steatosis (Niebergall & Vance, 2012) and a decrease in liver PC has been observed in human cases of hepatic steatosis (Puri et al., 2007). Moreover, a recent review (van der Veen et al., 2017) highlighted the importance of the cellular molar PC/PE ratio in the development of hepatic steatosis.…”

Lyso‐phosphatidylcholine: A potential metabolomic biomarker for alcoholic liver disease?

“…More recently (3) lower LYPC levels were found in nonalcoholic fatty liver disease/nonalcoholic steatohepatitis patients compared with controls. The link between LPS and LYPC is considered to be phosphatidylcholine-specific phospholipase C, the levels and activity of which are increased by LPS.…”