Susceptibility of Different Mouse Wild Type Strains to Develop Diet-Induced NAFLD/AFLD-Associated Liver Disease

Abstract

Although non-alcoholic and alcoholic fatty liver disease have been intensively studied, concerning pathophysiological mechanisms are still incompletely understood. This may be due to the use of different animal models and resulting model-associated variation. Therefore, this study aimed to compare three frequently used wild type mouse strains in their susceptibility to develop diet-induced features of non-alcoholic/alcoholic fatty liver disease. Fatty liver disease associated clinical, biochemical, and histological features in C57BL/6, CD-1, and 129Sv WT mice were induced by (i) high-fat diet feeding, (ii) ethanol feeding only, and (iii) the combination of high-fat diet and ethanol feeding. Hepatic and subcutaneous adipose lipid profiles were compared in CD-1 and 129Sv mice. Additionally hepatic fatty acid composition was determined in 129Sv mice. In C57BL/6 mice dietary regimens resulted in heterogeneous hepatic responses, ranging from pronounced steatosis and inflammation to a lack of any features of fatty liver disease. Liver-related serum biochemistry showed high deviations within the regimen groups. CD-1 mice did not exhibit significant changes in metabolic and liver markers and developed no significant steatosis or inflammation as a response to dietary regimens. Although 129Sv mice showed no weight gain, this strain achieved most consistent features of fatty liver disease, apparent from concentration alterations of liver-related serum biochemistry as well as moderate steatosis and inflammation as a result of all dietary regimens. Furthermore, the hepatic lipid profile as well as the fatty acid composition of 129Sv mice were considerably altered, upon feeding the different dietary regimens. Accordingly, diet-induced non-alcoholic/alcoholic fatty liver disease is most consistently promoted in 129Sv mice compared to C57BL/6 and CD-1 mice. As a conclusion, this study demonstrates the importance of genetic background of used mouse strains for modeling diet-induced non-alcoholic/alcoholic fatty liver disease.

Social stress shortens lifespan in mice

“…The vulnerability to HFD‐induced obesity was similar among the two groups probably due to the large hyperphagia shown by the dominant mice (Figure 3b,c). This finding in the C57BL/6J strain is at variance with previous data obtained in CD1 mice (Sanghez et al., 2013; Bartolomucci et al., 2009) thus suggesting a strain difference in metabolism (Fengler et al., 2016; Zou et al., 2013). …”

Impact of Fabp1/Scp-2/Scp-x gene ablation (TKO) on hepatic phytol metabolism in mice

“…Finally, phytol-diet alone greatly reduced hepatic triacylglyceride accumulation by 77% in WT males, and less so, by 52% in WT females (52). Because nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic lipid accumulation, these studies suggested that the lower hepatic expression of FABP1, SCP-2, and SCP-x in WT females may make females more susceptible to NAFLD, correlating with high-fat-induced NAFLD in some strains of female (73), but not male, mice (74), as well as with the higher prevalence of NAFLD in women (74,75). Furthermore, phytol-diet made WT mice less susceptible to hepatic triacylglyceride accumulation, more so males than females and correlated with WT females having lower hepatic expression of FABP1, SCP-2, and SCP-x than WT males (60,61).…”

Reducing endogenous insulin is linked with protection against hepatic steatosis in mice

“…Considering the strong positive association of age with hepatic steatosis in rodents and humans [20][21][22] , 30 week-old male C57BL/6J mice that transgenically express Ad36E4orf1 protein (E4orf1-Tg, n = 15) in the adipose tissue upon doxycycline induction 13 and age-matched wild-type (WT, n = 15) counterparts (Jackson Laboratory) were offered chow-doxycycline diet (chow-dox, 16% Kcal from fat, dox 600 ppm/kg) for 6 weeks followed by 10 weeks of HFdoxycycline diet (HF-dox, 60% Kcal from fat, dox 600 ppm/ kg). All animals were housed in the same room ≤5 mice/ cage on a 12-h light/12-h dark cycle, had ad libitum access to food, and received humane care.…”