Researchers: ethyl lactate ameliorates liver injury and alcohol-associated liver disease

A research team led by Prof. LI Yu from the Shanghai Institute of Nutrition and Health (SINH) of the Chinese Academy of Sciences (CAS) and collaborators have discovered that ethyl lactate, a key nonethanol ingredient found in distilled liquors, ameliorates alcoholic hepatic steatosis (fatty liver), inflammation, and acute-on-chronic liver injury in alcohol-associated liver disease (ALD). The study was published online in Advanced Science.

Increasing global alcohol exposure has aggravated the global prevalence of ALD. Aberrant upregulation of hepatic lipogenesis induced by excessive alcohol consumption is a critical driver of the progression of ALD, and the severity of ALD is highly dependent on the level of alcohol intake. Distilled spirits, with higher ethanol content than wine and beer, may increase the potential for more ethanol ingestion. Currently, there are no effective therapeutic approaches to limiting lipogenesis in ALD patients. 

Alcoholic beverages are complex mixtures of water, ethanol, and nonethanol ingredients. Due to their various raw materials, fermentation processes, and aging processes, distilled spirits produce abundant nonethanol ingredients such as esters, acids, higher alcohols, and aldehydes. These nonethanol ingredients determine the quality, type, taste, and flavor of various alcoholic beverages. However, whether nonethanol ingredients in alcoholic beverages regulate the pathogenesis of ALD has largely remained unclear. 

In this study, researchers first identified 40 chemical compounds in five widely consumed distilled spirits, i.e., whisky, brandy, baijiu, rum, and vodka, using gas chromatography with flame ionization detection (GC-FID) and high-performance liquid chromatography with ultraviolet detection (HPLC-UV). Thirteen chemical compounds were identified as the main nonethanol ingredients of distilled spirits, based on their concentrations. 

To investigate the roles of these nonethanol ingredients in regulating the pathogenesis of ALD, the researchers performed in vivo screening by using a mouse model of chronic-plus-binge ethanol feeding (also known as the Gao-Binge Model). They found that ethyl lactate, alone among these thirteen compounds, ameliorates hepatic steatosis, inflammation, and acute-on-chronic liver injury in a dose-dependent manner. 

Mechanistically, researchers found that ethyl lactate ameliorates hepatic steatosis and acute-on-chronic liver injury in ALD by inducing fibroblast growth factor 21 (FGF21), which inhibits alcohol-induced aberrant activation of mTORC1 (the mechanistic Target of Rapamycin Complex 1, a protein complex that serves as a cellular regulator of growth, metabolism, and protein synthesis), and hepatic lipogenesis. 

Interestingly, ethyl lactate is widely present not only in alcoholic beverages but also in other fermented foods such as vinegar, bread, and sausages. It is also a recognized food flavoring agent. 

This study advances the understanding of the foodborne small molecule ethyl lactate in regulating the progression of ALD, and may provide a new strategy for the prevention and treatment of ALD as well as obesity-related metabolic disorders.