Research Article: Influence of nicotine on choline-deficient, L-amino acid-defined diet-induced non-alcoholic steatohepatitis in rats

Date Published: June 29, 2017

Publisher: Public Library of Science

Author(s): Hiroyuki Kanamori, Yukiomi Nakade, Taeko Yamauchi, Kazumasa Sakamoto, Tadahisa Inoue, Takaya Yamamoto, Yuji Kobayashi, Norimitsu Ishii, Tomohiko Ohashi, Kiyoaki Ito, Yoshio Sumida, Haruhisa Nakao, Yoshitaka Fukuzawa, Masashi Yoneda, Pavel Strnad.

http://doi.org/10.1371/journal.pone.0180475

Abstract

Nicotine, a major compound in cigarette smoke, decreases food intake and body weight gain in mammals; however, the influence of nicotine on the progression of non-alcoholic steatohepatitis (NASH) remains controversial. This study aimed to investigate the effect of nicotine on NASH in rat models. Male Wistar rats were fed choline-deficient, l-amino acid-defined (CDAA) diet and treated with nicotine or saline. Food intake, body weight gain, presence of hepatic steatosis, inflammation, and fibrosis were assessed 6 weeks after the rats were fed CDAA diet. Hepatic branch vagotomy was performed to elucidate the mechanism through which nicotine affected steatohepatitis.

Partial Text

With the increased occurrence of the metabolic syndrome, the incidence of non-alcoholic fatty liver disease (NAFLD) has also dramatically increased in recent years, becoming a major health issue and the most common liver disease worldwide [1, 2]. Non-alcoholic steatohepatitis (NASH), which is characterized by steatosis, necroinflammation, and cytopathic changes, causes liver cirrhosis and lies within the NAFLD spectrum [3]. Although the pathogenesis of NASH remains elusive, an accumulation of excess lipids in the liver may be a prerequisite for developing NASH [4].

The CDAA-diet-fed rats co-administered with saline showed a significantly reduced body weight gain compared to that of CSAA-diet-fed rats co-administered with saline (Table 2), whereas the food intake of the CDAA diet-fed rats co-administered with saline was comparable to that of CSAA-diet-fed rats co-administered with saline (Table 2). While the CSAA diet did not induce hepatic steatosis, the CDAA diet induced hepatic steatosis, which was assessed by the levels of hepatic TG and Oil Red O staining (Table 2, Table 3, Fig 1A and 1B). The levels of hepatic TG and FFA in CDAA-diet-fed rats co-administered with saline were significantly higher than those in CSAA-diet-fed rats co-administered with saline (Table 2). On the contrary, the serum levels of TG in CDAA-diet-fed rats co-administered with saline were significantly lower than those in CSAA-diet-fed rats co-administered with saline (Table 2). Serum levels of ALT in CDAA-diet-fed rats co-administered with saline were significantly higher than those in CSAA-diet-fed rats co-administered with saline (Table 2).

In this study, we showed that continuous administration of nicotine improved CDAA diet-induced hepatic steatosis and inflammation, and decreased the levels of hepatic TG, FFA, and the number of CD68-positive macrophages. We also demonstrated that nicotine administration significantly reduced body weight gain and food intake in CDAA diet-fed rats. A previous report indicated that nicotine administration improves obesity, hepatic steatosis, and serum lipid profile by decreasing food intake in high fat diet (HFD)-induced obese rats [11]. Conversely, Friedman et al. showed that HFD, co-administered with nicotine, produced higher levels of lipid accumulation in the liver compared to those fed with HFD alone [18]. While Friedman et al. administered nicotine at a dose of 0.75 mg/kg, which could not change food intake, other investigators administered nicotine at doses of at least 1.5 mg/kg, which attenuates food intake [11, 18, 19]. These differences in the doses of nicotine may affect food intake in rodents.

 

Source:

http://doi.org/10.1371/journal.pone.0180475

 

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