Approximately 40∼50% of East Asians carry an inactive ALDH2 gene and exhibit acetaldehyde accumulation after alcohol consumption. However, the role of ALDH2 deficiency in the pathogene-sis of alcoholic liver injury remains obscure. METHODS: Wild-type (WT) and ALDH2-/- mice were subjected to ethanol feeding and/or carbon tetrachloride (CCl4) treatment, and liver injury was assessed. RESULTS: Compared with WT mice, ethanol-fed ALDH2-/- mice had higher levels of malondialde-hyde and acetaldehyde (MAA) adduct and greater hepatic inflammation, with higher hepatic interleukin-6 (IL-6) expression but surprisingly lower levels

of steatosis and serum alanine transaminase (ALT). Higher IL-6 levels were also detected in ethanol-treated, precision-cut liver slices from ALDH2-/- mice and in Kupffer cells isolated from ethanol-fed ALDH2-/- mice than those levels in WT mice. In vitro incubation with MAA enhanced the LPS-mediated Lapatinib stimulation of IL-6 production in Kupffer cells. In agreement with these findings, hepatic activation of the major IL-6 downstream signaling molecule signal transducer and activator of transcription 3 (STAT3) was higher in ethanol-fed ALDH2-/- mice than in WT mice. An additional deletion of hepatic STAT3 resulted in teatosis and hepatocellu-lar damage in ALDH2-/- mice. Finally,

ethanol-fed ALDH2-/-mice were more prone to CCl4-induced liver inflammation and fibrosis than ethanol-fed WT mice. CONCLUSIONS: ALDH2-/-mice are resistant to ethanol-induced steatosis medchemexpress but prone to inflammation and fibrosis via MAA-mediated paracrine activation of IL-6 in Kupffer cells. These findings suggest that individuals who have ALDH2 deficiency may be resistant Sunitinib manufacturer to steatosis, but are more prone to liver inflammation and fibrosis following alcohol consumption. Disclosures: The following people have nothing to disclose: Hyo-Jung Kwon, Young-Suk Won, Ogyi Park, Michael J. Duryee, Geoffrey Thiele, Akiko Matsumoto, Surendra Singh, Toshihiro

Kawamoto, Mohamed A. Abdelmegeed, Byoung-Joon Song, Vasilis Vasiliou, Geoffrey M. Thiele, Bin Gao Background: Under physiological state, free fatty acids (FFA) enter adipocytes and stored in the adipose tissues in the form of triglycerides (TG). Patients with alcoholic liver disease have been shown to have significantly lower percentage of body fat (%BF). This results in reducing TG storage as reflected by increasing serum FFA. In adipose tissue, Pref-1 is specifically expressed in preadipocytes but not in adipocytes. Increasing Pref-1 leads to inhibition of adipogenesis and reduced adipose tissue mass. Our aim is to investigate the association between alcohol consumption, serum Pref-1, and %BF in heavy drinkers compared to controls. Methods: 97 chronic heavy drinkers (mean age 41.3 years/69% men/81% Caucasian) were enrolled from Fairbanks Alcohol Treatment Center. 51 non-heavy drinkers (mean age 31.8 years/88% men/84% Caucasian) were recruited from Roudebush VAMC.