Dietary α-linolenic acid-rich flaxseed oil prevents against alcoholic hepatic steatosis via ameliorating lipid homeostasis at adipose tissue-liver axis in mice.

Key Findings

Consistently excessive alcohol intake leads to alcoholic liver disease (ALD) which includes liver damage from simple steatosis (fatty liver) to hepatitis, progressive fibrosis, and cirrhosis. Reducing alcohol-induced hepatic fat accumulation may block or delay the progression of steatosis to more advanced stages of ALD. Low levels of omega-3 polyunsaturated fatty acids (PUFAs), including α-linolenic acid (ALA, 18:3 n-3), in serum and liver tissue biopsies is common in patients with alcoholic and non-alcoholic liver disease. This study showed that flaxseed oil alleviated alcohol-induced hepatic steatosis by improving adipose function and lipid homeostasis at the adipose tissue-liver axis. Flaxseed oil reduced ethanol-stimulated adipose lipolysis by attenuating endoplasmic reticulum (ER) stress, leading to a reduced fatty acid influx to the liver. Adipose adiponectin production by up-regulating PPARG expression in adipose tissue and activating AMPK in the liver was also a result. The protective effect of dietary flaxseed oil was attributed to ALA itself and its conversion to EPA.

ABSTRACT

Low levels of n-3 polyunsaturated fatty acids (PUFAs) in serum and liver tissue biopsies are the common characteristics in patients with alcoholic liver disease. The α-linolenic acid (ALA) is a plant-derived n-3 PUFA and is rich in flaxseed oil. However, the impact of ALA on alcoholic fatty liver is largely unknown. In this study, we assessed the potential protective effects of ALA-rich flaxseed oil (FO) on ethanol-induced hepatic steatosis and observed that dietary FO supplementation effectively attenuated the ethanol-induced hepatic lipid accumulation in mice. Ethanol exposure stimulated adipose lipolysis but reduced fatty acid/lipid uptake, which were normalized by FO. Our investigations into the corresponding mechanisms demonstrated that the ameliorating effect of FO might be associated with the lower endoplasmic reticulum stress and normalized lipid metabolism in adipose tissue. In the liver, alcohol exposure stimulated hepatic fatty acid uptake and triglyceride synthesis, which were attenuated by FO. Additionally, dietary FO upregulated plasma adiponectin concentration, hepatic adiponectin receptor 2 expression, and the activation of hepatic adenosine monophosphate-activated protein kinase. Collectively, dietary FO protects against alcoholic hepatic steatosis by improving lipid homeostasis at the adipose tissue-liver axis, suggesting that dietary ALA-rich flaxseed oil might be a promising approach for prevention of alcoholic fatty liver.