Diet plays key role in liver problems in addition to alcohol, study says
29 Sep 2017 --- A new study published in Alcohol and Alcoholism has found that mice that consumed high amounts of alcohol, but had a healthy diet otherwise, did not necessarily develop the most severe liver injuries, suggesting that diet may play an important role in the development of liver issues.
Alcoholic liver disease is a global health burden and refers to a disease spectrum ranging from hepatomegaly and simple fatty liver (hepatic steatosis), to more severe pathologies such as alcoholic steatohepatitis and hepatic cirrhosis. In the US, about half of the population drinks alcohol and approximately 38 million people are estimated to engage in binge drinking behavior, according to the study’s Oxford University Press USA press release.
“The detrimental effects of sustained heavy alcohol intake on liver health are well established. However, animal models of alcohol-induced liver injury that replicate the human disease are more difficult to establish,” says the paper's lead author, Iain H. McKillop, Ph.D.
McKillop adds that the study’s collaborators at Indiana University – Purdue University Indianapolis (IUPUI) have developed a mouse model of alcohol intake that mirrors many of the characteristics of human alcohol consumption, in which mice given the choice between water and alcohol preferentially choose alcohol.
“Our data report that while cHAP mice drink more total alcohol than other models, the resulting degree of liver injury was less. These results suggest that other factors, such as dietary composition and/or genetic breeding leading to greater hepatic tolerance to alcoholic liver injury, may be involved,” McKillop says.
Diet aggravates liver injury
The new study sought to compare mice bred to preferentially consume high amounts of alcohol (crossed-High Alcohol Preferring, or cHAP, mice) to other mice using a chronic-binge ethanol ingestion model to induce alcoholic liver disease.
The mice were randomized and given different diets over a four-week period. Researchers collected tissue and serum. The researchers discovered that the cHAP mice on a diet of alcohol and water consumed significantly more alcohol than cHAP or other mice maintained on an alcohol diet.
However, cHAP and other mice on the alcohol diet together with the artificial sugar maltodextrin had greater hepatosteatosis and overall degree of liver injury compared to mice that consumed a diet of alcohol and water together with maltodextrin.
These data suggest factors other than the total amount of alcohol consumed may affect the degree of alcoholic liver disease development.
Additionally, this model may provide an additional rodent model to study the effects of ethanol on hepatic pathology that more closely mimics human patterns of ethanol consumption in heavy drinkers. This is because cHAP mice exhibit increasing ethanol consumption over time, consume ethanol in parallel with normal dietary intake and show higher levels of daily ethanol consumption than mice maintained on the controlled diet.
In discussing these outcomes, the authors speculated saturated fat in the diet of the standard rodent chow used, and epigenetic changes during strain development, may have accounted for lack of liver injury.
This position is corroborated by studies demonstrating a protective role for saturated fats in chronic ethanol-fed rodents in which diminished inflammation and decreased micro- and macrovesicular steatosis occurs to promote hepatic fatty oxidation. Saturated fats may also inhibit the development of alcoholic liver disease by maintaining the growth of intestinal microbiota.
The findings suggest that although cHAP mice consume consistently high/sustained levels of ethanol, other factors such as disparities in specific dietary components, differences in the patterns of alcohol consumption, and timing of feeding relative to peak blood-alcohol content, alter the degree of liver injury in cHAP versus other mice.
“Translating these data to human studies – to understand the differing effects of alcohol consumption and patterns of drinking on the development and progression of liver disease – may identify risk factors other than total alcohol consumed for developing liver disease,” McKillop adds.
“A critical role of the gut microbiome and fecal metabolites is becoming increasingly appreciated,” write Irina Kirpich and Craig McClain in an editorial accompanying the study. “Marked differences in the composition of the diets used in this study may help explain why mice consuming the highest amounts of alcohol did not develop the most severe liver injury. Diet and microbiome may be important variables in the different outcomes observed in various experimental alcoholic liver disease models.”
