Modest effect of differential dietary vitamin A intake on the pathogenesis of alcohol‐associated liver disease

Abstract

AbstractBackgroundChronic alcohol consumption is a major public health issue. The primary organ damaged by alcohol abuse is the liver, leading to alcohol‐associated liver disease (ALD). ALD begins with hepatic steatosis and can progress to fibrosis and cirrhosis; however, we have an incomplete understanding of ALD pathogenesis. Interestingly, the liver is also the major organ for vitamin A metabolism and storage, and ALD has previously been linked with altered hepatic vitamin A homeostasis. We hypothesize that alcohol‐induced vitamin A depletion disrupts its normal function in the liver, contributing to the pathogenesis of ALD. To test this hypothesis, we postulated that adding copious vitamin A to the diet might alleviate ALD, and conversely, that a vitamin A deficient diet would worsen ALD.MethodsWe conducted two dietary intervention studies in mice comparing deficient (0 IU/g diet) and copious (25 IU/g diet) dietary vitamin A intake versus control (4 IU/g diet), using the NIAAA chronic‐binge model of ALD. Hepatic steatosis was assessed using histopathological and biochemical approaches. Tissue Vitamin A levels were measured using high‐performance liquid chromatography. Markers of ALD, hepatic inflammation and lipid metabolism were analyzed by the quantitative polymerase chain reaction and western blotting.ResultsAs expected, a 0 IU/g Vitamin A diet decreased, and a 25 IU/g Vitamin A diet increased hepatic Vitamin A stores. However, alcohol induced changes in hepatic triglyceride levels, markers of hepatic lipid metabolism, inflammation and fibrosis were not significantly different in mice consuming a copious or deficient vitamin A diet compared to control.ConclusionsAltered vitamin A intake and hepatic vitamin A storage have a minor effect on the pathogenesis of ALD. Thus, given the known link between altered retinoic acid signaling and ALD, future studies that further explore this linkage are warranted.