Determining the Effect of Diet on Liver and Renal Health in a Mouse Model of Chronic Alcohol Intake

Abstract

Diet and alcohol consumption are significant contributors to health and disease worldwide. Liver disease is a consequence of poor diet and alcohol consumption; however preclinical animal studies have not adequately considered the combined effect of poor diet and chronic alcohol intake into study design. Given the physiological cross talk between the liver and kidney and the occurrence of hepatorenal syndrome in alcoholics, we set out to determine how poor diet and chronic alcohol intake influence liver and kidney health in mice. All experiments were performed in accordance with protocols approved by the Liberty University IACUC and conform to the FASEB standards for the use of animals in research and education. 3‐week old male C57Bl/6 mice were purchased from The Jackson Laboratory and acclimated to the new environment and chow diet for 1‐week. Mice were then given ad libitum access to chow (18% protein), our novel Americanized diet (AD), or a commercially available “Western” diet (WD) (n=6). After 6 weeks, all mice began a chronic alcohol exposure of 10% ethanol solution given as the only source of water for 3 weeks. Body weight, food, and beverage intake were recorded weekly. Systolic blood pressure was determined using a non‐invasive tail‐cuff method and renal blood flow estimated using contrast‐enhanced ultrasonography. Mice were then euthanized and blood and liver tissues collected. Blood was analyzed for circulating ALT activity and HDL, triglycerides, and glucose concentrations. All statistical analyses were performed using general linear models in SPSS with “Diet” as the independent variable. Diet had a significant effect on ethanol consumption (P<0.001), with mice fed chow having the highest ethanol intake (6 mg ethanol/g body weight) as compared to mice fed the WD (3.4 mg/g). Mice fed the WD had the greatest body weight, dietary intake, adiposity, and circulating HDL concentration as compared to mice fed chow (P<0.001). Mice fed chow had the highest circulating glucose levels (P<0.001). Histological analyses revealed excessive hepatic steatosis as the primary finding and was most severe in mice fed WD. No overt changes were noted in mice fed chow. Circulating ALT activity was elevated in mice fed the WD as compared to mice fed AD or chow, further suggesting increased liver injury in these mice. Mice fed the AD had intermediate values for all measurements with the exception of systolic blood pressure. Mice fed the AD had a 10 mmHg increase in systolic pressure as compared to mice fed chow or the WD (P=0.03). This occurred despite a lack of difference in renal hemodynamics between the different dietary groups (P≥0.3). Our data suggest that diet and alcohol have an additive effect in regards to liver damage and the development of metabolic dysfunction. The physiological mechanism by which consumption of our novel AD caused moderate hypertension in mice when combined with chronic alcohol intake will be pursued in future studies. Taken together, our findings highlight the need to consider the role of diet in preclinical animal models studying the physiological effects of chronic alcohol intake.Support or Funding InformationLUCOM Intramural Grant #2018‐01.This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.