title: Cigarette smoking exacerbates nonalcoholic fatty liver disease in obese rats.
abstract: The prevalence of cigarette smoking (CS) is increased among obese subjects, who are susceptible to develop nonalcoholic fatty liver disease (NAFLD). We investigated the hepatic effects of CS in control and obese rats. Control and obese Zucker rats were divided into smokers and nonsmokers (n = 12 per group). Smoker rats were exposed to 2 cigarettes/day, 5 days/week for 4 weeks. The effects of CS were assessed by biochemical analysis, hepatic histological examination, immunohistochemistry, and gene expression analysis. Phosphorylation of AKT and extracellular signal-regulated kinase (ERK) and quantification of carbonylated proteins were assessed by western blotting. As expected, obese rats showed hypercholesterolemia, insulin resistance, and histological features of NAFLD. Smoking did not modify the lipidic or glucidic serum profiles. Smoking increased alanine aminotransferase serum levels and the degree of liver injury in obese rats, whereas it only induced minor changes in control rats. Importantly, CS increased the histological severity of NAFLD in obese rats. We also explored the potential mechanisms involved in the deleterious effects of CS. Smoking increased the degree of oxidative stress and hepatocellular apoptosis in obese rats, but not in controls. Similarly, smoking increased the hepatic expression of tissue inhibitor of metalloproteinase-1 and procollagen-alpha2(I) in obese rats, but not in controls. Finally, smoking regulated ERK and AKT phosphorylation. The deleterious effects of CS were not observed after a short exposure (5 days).
  
  
  CONCLUSIONS
  CS causes oxidative stress and worsens the severity of NAFLD in obese rats. Further studies should assess whether this finding also occurs in patients with obesity and NAFLD.
authors.affiliation: Centro de Investigación Biomédica En Red de Enfermedades Hepáticas y Digestivas, Institut D'Investigacions Biomèdiques August Pi i Sunyer, and Liver Unit, Hospital Clínic, Barcelona, Catalonia, Spain.
authors.forename: Lorenzo
authors.initials: L
authors.lastname: Azzalini
authors.forename: Elisabet
authors.initials: E
authors.lastname: Ferrer
authors.forename: Leandra N
authors.initials: LN
authors.lastname: Ramalho
authors.forename: Montserrat
authors.initials: M
authors.lastname: Moreno
authors.forename: Marlene
authors.initials: M
authors.lastname: Domínguez
authors.forename: Jordi
authors.initials: J
authors.lastname: Colmenero
authors.forename: Víctor I
authors.initials: VI
authors.lastname: Peinado
authors.forename: Joan A
authors.initials: JA
authors.lastname: Barberà
authors.forename: Vicente
authors.initials: V
authors.lastname: Arroyo
authors.forename: Pere
authors.initials: P
authors.lastname: Ginès
authors.forename: Joan
authors.initials: J
authors.lastname: Caballería
authors.forename: Ramón
authors.initials: R
authors.lastname: Bataller
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005234:Fatty Liver / Q000209:etiology*; D009765:Obesity / Q000150:complications / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D011924:Rats, Zucker; D012907:Smoking / Q000009:adverse effects*; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000096:biosynthesis
chemical_list: D019715:Tissue Inhibitor of Metalloproteinase-1