Modest effect of differential dietary vitamin A intake on the pathogenesis of alcohol-associated liver disease.
Alcohol Clin Exp Res (Hoboken)
; 48(6): 1036-1049, 2024 Jun.
Article
en En
| MEDLINE
| ID: mdl-38649284
ABSTRACT
BACKGROUND:
Chronic 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.METHODS:
We 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.RESULTS:
As 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.CONCLUSIONS:
Altered 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.
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Idioma:
En
Revista:
Alcohol Clin Exp Res (Hoboken)
Año:
2024
Tipo del documento:
Article
País de afiliación:
Canadá
Pais de publicación:
Estados Unidos