Abstract
Non-alcoholic fatty liver disease (NAFLD) poses a serious health hazard affecting 20–40% of adults in the general population in the USA and over 70% of the obese and extremely obese people. In addition to obesity, nicotine is recognized as a risk factor for NAFLD, and it has been reported that nicotine can exaggerate obesity-induced hepatic steatosis. The development of NAFLD has serious clinical complications because of its potential progression from simple hepatic steatosis to non-alcoholic steatohepatitis (NASH), liver cirrhosis, and hepatocellular carcinoma. Multiple mechanisms can be involved in nicotine plus high-fat diet-induced (HFD) hepatic steatosis. Emerging evidence now suggests that nicotine exacerbates hepatic steatosis triggered by HFD, through increased oxidative stress and hepatocellular apoptosis, decreased phosphorylation (inactivation) of adenosine-5-monophosphate-activated protein kinase and, in turn, up-regulation of sterol response-element binding protein 1-c, fatty acid synthase, and activation of acetyl-coenzyme A-carboxylase, leading to increased hepatic lipogenesis. There is also growing evidence that chronic endoplasmic reticulum stress through regulation of several pathways leading to oxidative stress, inflammation, perturbed hepatic lipid homeostasis, apoptosis, and autophagy can induce hepatic steatosis and its progression to NASH. Evidence also suggests a central role of the gut microbiota in obesity and its related disorders, including NAFLD. This review explores the contribution of nicotine and obesity to the development of NAFLD and its molecular underpinning.
Highlights
In 2009, approximately 20% (~60 million) of Americans smoked and about ~88 million non-smokers were exposed to secondhand smoke [1]
Non-alcoholic fatty liver disease is the most common liver disorder and is associated with metabolic syndrome and diabetes mellitus. It includes the whole spectrum of fatty liver, ranging from simple steatosis to steatohepatitis [non-alcoholic steatohepatitis (NASH)], which can progress to liver cirrhosis and hepatocellular carcinoma [20,21,22]
Animal experiments using first-hand, second-hand smoke, or nicotine and models of genetic or diet-induced obesity (DIO) provide perhaps the strongest evidence linking nicotine to hepatic steatosis and Non-alcoholic fatty liver disease (NAFLD)
Summary
In 2009, approximately 20% (~60 million) of Americans smoked and about ~88 million non-smokers were exposed to secondhand smoke [1]. Cigarette smoking is the leading preventable cause of death and disability worldwide [3, 4]. Smoking is a major risk factor for chronic obstructive pulmonary disease and lung cancer and devastating cardiovascular disease (CVD), such as myocardial infarction, sudden death, stroke, Obesity, Nicotine, and Hepatic Steatosis and peripheral vascular disease [5,6,7,8], with a dose–response correlation between CVD morbidity and mortality and the number of cigarettes smoked [8]. Nicotinic acetylcholine receptors (nAChRs) are a family of ionotropic receptor proteins formed by five homologous or identical subunits and are involved in signal transduction between neurons and muscle cells [10, 13, 14]. This review discusses emerging evidence of contribution of nicotine when combined with obesity to the development of hepatic steatosis and insights into the molecular mechanisms by which nicotine contributes to non-alcoholic fatty liver disease (NAFLD)
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