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 uncovered that ethyl lactate, a main nonethanol ingredient found in distilled liquors, lowers alcoholic hepatosteatosis, 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 aggravates global prevalence of ALD, which is a major cause of liver-related morbidity and mortality. Aberrant upregulation of hepatic lipogenesis induced by excessive alcohol consumption is a critical driver for the progression of ALD. Distilled spirits, with higher ethanol content than wine and beer, increase susceptibility to more ethanol ingestion and ALD pathogenesis.

Currently, there are no effective approaches available for the treatment of ALD patients. The severity of ALD is highly dependent on the amount of alcohol intake.

Alcoholic beverages are complex mixtures composed of water, ethanol and nonethanol ingredients. Due to the special types of raw materials, fermentation processes and aging processes, distilled spirits produce abundant nonethanol ingredients such as esters, acids, higher alcohols and aldehydes.

Among which, the nonethanol ingredients determine the unique quality, taste, flavor and types of alcoholic beverages. Whether the nonethanol ingredient in alcoholic beverages regulates the pathogenesis of ALD remains largely unknown.

In this study, researchers first identified 40 chemical compounds in five typical distilled spirits in the world, including whiskey, 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 with higher concentrations were defined as the main nonethanol ingredients of distilled spirits.

To investigate the roles of the main nonethanol ingredients in regulating pathogenesis of ALD, researchers performed in vivo screening by using the mouse model of chronic-plus-binge ethanol feeding (also known as Gao-Binge). They found that among these 13 compounds, ethyl lactate 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 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 foodborne small molecule ethyl lactate in regulating the progression of ALD, which may provide a new strategy for the prevention and treatment of ALD as well as obesity-related metabolic disorders.