A mouse model of weight gain after nicotine withdrawal

概要

Nagoya City University Academic Repository

学 位 の 種 類

博士 (医学)

報 告 番 号

甲第１８７６号

学 位 記 番 号

第１３３０号

氏

竹田 勝志

名

授 与 年 月 日

令和 4 年 3 月 24 日

A mouse model of weight gain after nicotine withdrawal
(禁煙後の体重増加の病態モデルとしての高脂肪食下ニコチン離脱マウス
の樹立と解析)
学位論文の題名
Biochemical and Biophysical Research Communications, 588: 140-146,
2022

論文審査担当者

主査：

新実 彰男

副査：

大石 久史, 瀧口 修司

Body weight gain after smoking cessation is often encountered in daily clinical practice and has
been reported in epidemiological studies. There is a report showing that cardiovascular
benefits of smoking cessation are compromised by weight gain. Other studies have shown that
weight gain after smoking cessation is accompanied by an increased risk of developing
newly-onset type 2 diabetes mellitus or the metabolic syndrome. Moreover, weight gain
following smoking cessation is associated with an increased risk of smoking relapse. Therefore,
development of effective measures to prevent weight gain after smoking cessation is in urgent
need. Underlying mechanisms, however, have not been fully understood. We here report an
establishment of a mouse model that exhibits an augmented body weight gain after nicotine
withdrawal. Male C57BL/6J mice were fed with high fat diet for four weeks, followed by
two-week nicotine infusion using osmotic minipumps. Mice were then treated for another two
weeks either with vehicle or nicotine by other sets of minipumps. Body weight was increased
immediately after nicotine withdrawal and significantly higher than that of mice continued on
nicotine. The amount of diet consumed during the first week after nicotine cessation was larger
in mice switched to vehicle, while oxygen consumption was comparable. Expression of
orexigenic agouti-related peptide was elevated in the hypothalamus. Pair-feeding experiment
revealed the accelerated weight gain after nicotine withdrawal is explained by enhanced food
intake. To showcase an efficacy of pharmacologic intervention, exendin-4, which is a
glucagon-like peptide-1 analog with a weight-reducing effect, was administered. Exendin-4
suppressed food intake and weight gain in mice withdrawn from nicotine. Therefore, our
current model provides a unique platform to investigate the basic mechanisms underlying an
alteration of energy metabolism just after smoking cessation. Furthermore, it can serve as an
ideal animal model to undertake proof-of-concept preclinical experiments for the development
of novel therapies to mitigate this health hazard. ...

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