College of Public Health Faculty Publish on Alcoholic Fatty Liver Disease

Dr. Yongke Lu, Assistant Professor in the Department of Health Sciences, and Dr. Kesheng Wang, Associate Professor in the Department of Epidemiology and Biostatistics of East Tennessee State University’s College of Public Health, identified a new signaling pathway that is associated with nicotine-enhanced alcoholic fatty liver. They discuss their research in an article entitled “Suppressed hepatocyte proliferation via a ROS-HNE-P21 pathway is associated with nicotine- and cotinine-enhanced alcoholic fatty liver in mice” that was published in Biochemical and Biophysical Research Communications. 

Alcohol drinking and tobacco smoking are two major public health issues and alcohol and tobacco are often co-abused. Previously, Dr. Lu’s lab found that nicotine enhanced alcoholic fatty liver in a CYP2A5-dependent manner. Cotinine, a major metabolite of nicotine, also enhances alcoholic fatty liver, for which CYP2A5 also plays an important metabolic role. Further study showed that lipid peroxidation caused by reactive oxygen species (ROS), a major cluster of free radicals generated during the process of nicotine and cotinine metabolism, may contribute to the nicotine-enhanced alcoholic fatty liver. 

In this study, the authors applied RNA-Seq analysis to further identify the ROS-induced hepatic genes that potentially contribute to nicotine- and cotinine-enhanced alcoholic fatty liver. RNA-Seq analysis indicates that cell proliferation inhibitory gene Cdkn1a (coding P21 protein) was upregulated by both nicotine and cotinine, which was confirmed by elevated P21 protein and reduced PCNA and Ki67, two major markers of hepatocyte proliferation. Inhibited hepatocyte proliferation is associated with alcoholic fatty liver. Interestingly, lipid peroxidation end product 4-hydroxynonenal (HNE), an inducer of Cdkn1a, was increased by nicotine and cotinine. Thus, a ROS-HNE-P21 axis was identified to be related to nicotine- and cotinine-enhanced alcoholic fatty liver. 

Biochemical and Biophysical Research Communications is a premier international journal devoted to the very rapid dissemination of timely and significant experimental results in diverse fields of biological research.