Browsing by Subject "Lipidexport"

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Geschlechtsspezifische Unterschiede in der Entstehung von alkoholbedingten Lebererkrankungen
(2010) Wagnerberger, Sabine; Bode, Christiane
Women are assumed to have a higher susceptibility to alcohol-induced liver disease (ALD) than men. Gender-related differences in food preference were described in previous studies for several populations. As certain micronutrients are reported to take influence on the development of ALD in animal experiments, the hypothesis of the present retrospective cross-sectional study was that gender-dependent (micro-) nutrient intake in patients with ALD may cause the higher susceptibility of women to this disease. In 210 patients (male: 158, female: 52) with different stages of ALD (ALD1: mild stage of liver damage; ALD2: moderately severe changes of the liver with signs of hepatic inflammation; ALD3: severely impaired liver function) and in 336 controls (male: 208, female: 128), nutrient intake was determined by a computer-guided diet history and related to the severity of ALD in dependence on the sex of the patients. No significant differences between males and females with ALD were calculated for the intake (per kg body/day) of protein, carbohydrates, fat, and the intake (per kg body/day) of most micronutrients. In females with ALD, higher intake was found for vitamin C (ALD3), calcium (ALD2), iron (ALD1 and ALD2), and zinc (ALD1), but the consumption of none of these micronutrients seems to contribute to a higher susceptibility to ALD in females. In the present study, a higher activity of ?liver-specific? enzymes and a higher DeRitis quotient was measured in female patients with ALD despite equal or lower amounts of consumed alcohol. This may indicate a higher susceptibility to the development of ALD in women. However, the data of calculated daily macro- and micronutrient intake do not suggest any explicit influence of gender-specific nutrition in the development of ALD. In a chronic setting of alcohol intake, women and female rodents are more susceptible to alcohol-induced liver disease than men and male mice. Starting from this background, the purpose of the present study was to determine if female mice are also more susceptible to acute alcohol-induced steatosis than male mice and to investigate whether this is due to alterations in hepatic lipid export. Male and female C57/Bl6-mice received one single dose of ethanol (6 g/kg) or isocaloric maltose-dextrin solution (control) intragastrically. Hepatic triglycerides, lipid accumulation, mRNA expression of microsomal triglyceride transfer protein (MTP) and apolipoprotein (Apo) B, as well as MTP activity were measured 12, 24, and 48 h after alcohol intake. In both genders, acute alcohol ingestion markedly increased hepatic lipid and triglyceride levels; however, total lipid accumulation was ~2-fold higher and more persistent in livers of female than in male mice. Fourty-eight h after ethanol treatment hepatic triglyceride concentrations in male and female ethanol-treated mice were similar to those of controls. MTP activity was significantly increased only in male mice 12 h after ethanol ingestion; whereas expression of MTP mRNA was significantly reduced in female alcohol-treated animals compared to controls at this timepoint. Expression of ApoB was also reduced only in livers of female mice after 12 h; however, differences did not reach level of significance. The results of the present study suggest that the markedly more pronounced and more prolonged susceptibility to acute alcohol-induced liver steatosis of female mice results at least partly from a gender-specific regulation of hepatic lipid export. In our experiments, the selective estrogen recepor modulator (SERM) toremifen did not protect against alcohol-induced hepatic lipid accumulation. The liver plays an important role not only in the metabolism of ethanol but also in the immune system. Lymphatic NK cells are present at an unusually high frequency among liver-resident lymphocytes (30-50 %). By producing the pro-inflammatoric and anti-fibrotic cytokine IFN-g NK cells are involved in the development of liver diseases. Results of studies of our own working group indicate a decrease of IL-12-induced IFN-g production in NK-92 cells after treatment with ethanol for 6 h. The aim of the present study was to investigate whether male (testosterone) or female (estrogen, progesterone, FSH, LH) sex hormones influence the ethanol-induced immunosuppression in NK-92 cells. Therefore, NK-92 cells were incubated with different sex hormones for 19 h and were subsequently treated with ethanol (1-3 ?) and sex hormones for 18 h. Concentrations of IFN-g were determined by ELISA. According to previous studies ethanol treatment resulted in a significant decrease of released IFN-g in comparison to NK-92 cells that were not incubated with ethanol. However, treatment with male and female sex hormones did not affect IFN-g release in NK-92 cells. The results of the present study suggest that solely ethanol treatment but not incubation with sex hormones has an immun modulating effect on NK-92 cells.