Alcohol produces distinct hepatic lipidome and eicosanoid signature in lean and obese

Puneet Puri,Jun Xu,Terhi Vihervaara,Riikka Katainen,Kim Ekroos,Kalyani Daita,Hae-Ki Min,Andrew Joyce,Faridoddin Mirshahi,Hidekazu Tsukamoto,Arun J Sanyal

doi:10.1194/jlr.m066175

Abstract

Alcohol- and obesity-related liver diseases often coexist. The hepatic lipidomics due to alcohol and obesity interaction is unknown. We characterized the hepatic lipidome due to 1) alcohol consumption in lean and obese mice and 2) obesity and alcohol interactions. In the French-Tsukamoto mouse model, intragastric alcohol or isocaloric dextrose were fed with either chow (lean) or high-fat, high-cholesterol diet (obese). Four groups (lean, lean alcohol, obese, and obese alcohol) were studied. MS was performed for hepatic lipidomics, and data were analyzed. Alcohol significantly increased hepatic cholesteryl esters and diacyl-glycerol in lean and obese but was more pronounced in obese. Alcohol produced contrasting changes in hepatic phospholipids with significant enrichment in lean mice versus significant decrease in obese mice, except phosphatidylglycerol, which was increased in both lean and obese alcohol groups. Most lysophospholipids were increased in lean alcohol and obese mice without alcohol use only. Prostaglandin E2; 5-, 8-, and 11-hydroxyeicosatetraenoic acids; and 9- and 13-hydroxyoctadecadienoic acids were considerably increased in obese mice with alcohol use. Alcohol consumption produced distinct changes in lean and obese with profound effects of obesity and alcohol interaction on proinflammatory and oxidative stress-related eicosanoids.

Highlights

Alcohol- and obesity-related liver diseases often coexist
nonalcoholic fatty liver disease (NAFLD) was defined as a condition with a spectrum of liver histology similar to that seen in alcoholic liver disease (ALD) but occurred in the absence of alcohol consumption in amounts that was considered harmful [4]
The total hepatic 13-HODE, increased only in obese versus lean mice (+86% difference, P = 0.04) (Fig. 4C). Both ALD and NAFLD are associated with increased steatosis, cell death, and inflammation

Summary

Introduction

Alcohol- and obesity-related liver diseases often coexist. The hepatic lipidomics due to alcohol and obesity interaction is unknown. ALD and NAFLD are considered to represent distinct conditions separated by the amount of alcohol consumed despite having similar liver histology Implicit in this concept is that these conditions have a distinct molecular and physiological basis for disease development. It is no surprise that alcohol use Abbreviations: AA, arachidonic acid; ALD, alcoholic liver disease; CE, cholesteryl ester; COX, cyclooxygenase; CYP450, cytochrome P450; DAG, diacylglycerol; DHET, dihydroxyeicosatrienoic acid; EET, epoxyeicosatrienoic acid; ES, external standard; HEPE, hydroxyeicosapentaenoic acid; HFCD, high-fat, high-cholesterol diet; 9-HODE, 9-hydroxy-10,12-octadecadienoic acid; 13-HODE, 13-hydroxy-9,11-octadecadienoic acid; iG, intragastric; IS, internal standard; LA, lean alcohol; LOX, lipoxygenase; LPC, lyso-PC; LPE, lyso-PE; LPG, lyso-PG; LPI, lyso-PI; NAFLD, nonalcoholic fatty liver disease; OA, obese alcohol; PC, phosphatidylcholine; PE, phosphatidylethanolamine; PG, phosphatidylglycerol; PGD2, prostaglandin D2; PGE2, prostaglandin E2; PGF2 , prostaglandin F2 ; PI, phosphatidylinositol; SPE, solid-phase extraction

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