Key result
Nicotine administration primarily affected mediastinal brown adipose tissue in male rats, decreasing vacuolation and norepinephrine turnover while increasing UCP-1 and norepinephrine content.
Why the study?
Does nicotine affect norepinephrine metabolism and UCP-1 expression in rat brown adipose tissue?
Does nicotine affect norepinephrine metabolism and UCP-1 expression in rat brown adipose tissue?
Nicotine primarily affects mediastinal brown adipose tissue in male rats, providing a potential mechanistic explanation for the gender and location of hibernomas observed in varenicline carcinogenicity studies.
May explain male rat hibernoma findings in varenicline studies; leaves open human relevance.
In a two-year carcinogenicity study with administration of high doses of the partial nicotinic agonist varenicline (recently approved for smoking cessation), mediastinal hibernomas occurred in three male rats. To investigate potential mechanisms for partial and full nicotinic agonists to contribute to development of hibernomas, the effects of nicotine on rat brown adipose tissue (BAT) were studied. Male and female rats were administered nicotine at doses of 0, 0.3, and 1 mg/kg subcutaneously for fourteen days. Intrathoracic (mediastinal periaortic and mediastinal perithymic) BAT and interscapular BAT were examined microscopically, and determinations of uncoupling protein-1 (UCP-1) expression and norepinephrine (NE) content were made. Additionally, NE turnover was measured in mediastinal periaortic and perithymic BAT. Nicotine (1 mg/kg) administration resulted in decreased vacuolation only in mediastinal periaortic and mediastinal perithymic BAT of males and elevated UCP-1 in mediastinal periaortic BAT of males and females. Increased NE content occurred only in mediastinal periaortic BAT of males given 0.3 and 1 mg/kg doses, whereas NE turnover was decreased in both males and females given 1 mg/kg. Together, these data demonstrate that nicotine primarily affects mediastinal BAT in male rats, consistent with the gender and location of the hibernomas observed in the two-year carcinogenicity study.
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Brees et al. (2008) studied Hibernomas / Brown adipose tissue metabolism. Nicotine vs. 0 mg/kg (control) was evaluated on Brown adipose tissue (BAT) vacuolation, UCP-1 expression, and norepinephrine (NE) content and turnover. Nicotine administration primarily affected mediastinal brown adipose tissue in male rats, decreasing vacuolation and norepinephrine turnover while increasing UCP-1 and norepinephrine content.
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