Basic nutritional investigationAn iso-α-acid-rich extract from hops (Humulus lupulus) attenuates acute alcohol-induced liver steatosis in mice
Introduction
Despite intense awareness training and many campaigns warning of the consequences of heavy alcohol drinking [1], alcohol consumption is still one of the leading causes of liver diseases worldwide [2], [3]. However, results from epidemiologic and animal studies suggest that different alcoholic beverages (e.g., hard spirits and fermented beverages) might vary in regard to their potential to harm the liver. Indeed, results from an older, pooled, cross-sectional time-series analysis suggest that consumption of spirits rather than beer or wine is associated with cirrhosis mortality in primarily beer-drinking countries [4], whereas others found no differences between alcoholic beverages and their effect on the development of liver cirrhosis [5]. Studies in rodents using acute but also chronic alcohol-feeding models showed that chronic intake of red but not white wine is less harmful for the liver than consumption of comparable amounts of plain ethanol [6], [7]. Our own group recently reported that acute intake of large amounts of beer (e.g., doses equivalent to an acute consumption of ∼2.5 L of beer in humans) and herein especially Pilsner beer is associated with a markedly less pronounced fat accumulation in the liver when compared with the consumption of plain ethanol [8]. However, to our knowledge, compounds in beer responsible for its less harmful effects on the liver have not yet been identified.
Among the main compounds found in beer are carbohydrates, amino acids, and vitamins [9]; however, hops in beer is a rich source of secondary plant compounds like kaempferol, quercetin, xanthohumol, and α-acids [10]. Results of several in vitro and some in vivo studies suggest that beer constituents may modulate carcinogen metabolism and apoptosis and may possess antioxidative, antiinflammatory capacity, or both [11]. For instance, it has been shown that xanthohumol may inhibit the development of obesity, hepatic steatosis, and even fibrosis [12]. Results of recent studies suggest that iso-α-acids also may affect the liver. Indeed, Stärkel et al. showed that tetra- and hexahydro-iso-α-acids may inhibit proliferation of hepatoma cells and reduce liver tumor formation in rats [13]. Furthermore, it recently has been reported that when consumed at “normal” doses, iso-α-acids are found in blood and urine at measurable amounts even 6 h after consumption, further suggesting that these compounds may exert physiological effects for an extend period of time after ingestion [14]. However, it has not yet been clarified whether iso-α-acids have an effect on alcohol-induced liver steatosis.
Starting from this background, the aim of the present study was to determine whether pretreatment with iso-α-acids attenuates the development of acute alcohol-induced liver steatosis in a mouse model.
Section snippets
Animal protocols
Female C57 Bl/6 J mice (aged 6–7 wk, Janvier, France) were housed in an animal facility at standardized 12-h light/dark cycle, 40% to 60% humidity, and 22 ± 2°C room temperature. All animal protocols were approved by the local Institutional Animal Care and Use Committee. Animals had free access to drinking water and standard pellet chow (Ssniff, Soest, Germany) at all times. For the experiment, mice were divided in two groups (n = 16/group). One group was pretreated with the iso-α-acid–rich
Effects of pretreating mice with an iso-α-acid–rich extract on blood alcohol levels and hepatic fat accumulation 12 h after ethanol ingestion
Twelve hours after acute ingestion of ethanol, plasma ethanol levels of ethanol-fed mice, regardless of additional treatments, did not differ from those of controls (see Table 1). Lipid accumulation as determined by densitometric analysis of oil red O staining of liver sections and measurement of hepatic TG concentration was significantly higher in livers of ethanol-fed mice than in other groups (see Fig. 1). Although still being significantly higher than in controls, hepatic TG levels in
Discussion
In the present study, using a binge-drinking mouse model, we determined the effect of an extract rich in iso-α-acids [15] on the development of acute alcohol-induced liver steatosis. Indeed, despite showing similar signs of drunkenness and blood alcohol levels 12 h after the alcohol binge, pretreatment of mice with the iso-α-acid–rich extract markedly attenuated the alcohol-induced hepatic fat accumulation. However, oil red O staining and TG accumulation as well as Plin2, previously shown to be
Conclusion
Data from the present study suggested that iso-α-acids derived from hops might protect the liver, at least in part, from acute alcohol-induced fat accumulation. The results further suggested that an oral intake of an iso-α-acid–rich extract protects the liver from acute alcohol-induced steatosis through mechanisms involving protection against the activation of iNOS. However, whether only iso-α-acids or other compounds derived from hops found in the extract used (e.g., <0.3 β-acids and <0.7
Acknowledgments
The authors acknowledge the Barth-Haas-Group, Germany for providing Isohop.
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This work was supported by Wissenschaftsförderung der Deutschen Brauwirtschaft e.V. C.H. is a consultant of Joh. Barth & Sohn GmbH. I.B. receives funding from Yakult Honsha Co., Ltd.