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尼古丁剂量和给药频率对小鼠体重及脂肪组织的影响

Effects of Nicotine Doses and Administration Frequencies on Mouse Body Weight and Adipose Tissues.

作者信息

Qin Runwen, Zhang Yi, Xu Shihua, Mei Yingwu, Jin Ge, Mi Yang, Zhang Haifeng

机构信息

Department of Biochemistry and Molecular Biology, School of Basic Medical Sciences, Zhengzhou University, Zhengzhou, China.

出版信息

Nicotine Tob Res. 2025 Feb 24;27(3):484-493. doi: 10.1093/ntr/ntae208.

DOI:10.1093/ntr/ntae208
PMID:39233590
Abstract

INTRODUCTION

This study investigates the effects of varying nicotine doses and administration frequencies on mouse body weight, adipose tissues, and liver.

AIMS AND METHODS

Male C57BL6/J mice received subcutaneous nicotine doses (0.5, 1, or 2 mg/kg) once daily (qd), twice daily (bid), or four times daily (qid) for 4 weeks. Body weight, inguinal white adipose tissue (iWAT), epididymal white adipose tissue (eWAT), brown adipose tissue (BAT) weight and size, and UCP1 expression were assessed, along with liver fat deposition and morphology.

RESULTS

Nicotine administration reduced body weight and decreased the weight and size of iWAT and eWAT compared to controls. The frequency of nicotine administration had a more significant impact on body weight and fat tissues than the dosage itself, with 2 mg/kg bid being optimal for weight reduction. Nicotine increased BAT cell numbers and amplified UCP1 expression in iWAT and BAT. It had minor effects on eWAT UCP1 expression and no substantial impact on liver fat deposition or morphology, except for a reduction in liver weight with doses exceeding 4 mg/kg.

CONCLUSIONS

Nicotine-induced weight reduction is frequency-dependent, with 2 mg/kg bid being the optimal regimen. The mechanisms may include reductions in iWAT and eWAT weights and cell sizes, induction of browning in iWAT, increased BAT quantity and UCP1 expression, and heightened energy expenditure in iWAT and BAT. Nicotine's ability to induce eWAT browning is relatively weak, indicating diverse mechanisms of action across different adipose tissue types. These findings provide a foundation for further exploration of nicotine's multifaceted functions and underlying mechanisms.

IMPLICATIONS

This study examines how different nicotine doses and administration frequencies affect mouse body weight and adipose tissues. It finds that administering nicotine bid (twice daily) at 2 mg/kg leads to optimal weight reduction. Nicotine induces browning in white adipose tissue, increases BAT quantity and UCP1 expression, and affects energy expenditure. The findings underscore nicotine's nuanced effects across different adipose tissue types and lay the groundwork for further exploration of its mechanisms and therapeutic potential in weight management.

摘要

引言

本研究调查了不同尼古丁剂量和给药频率对小鼠体重、脂肪组织和肝脏的影响。

目的和方法

雄性C57BL6/J小鼠接受皮下注射尼古丁剂量(0.5、1或2毫克/千克),每日一次(qd)、每日两次(bid)或每日四次(qid),持续4周。评估体重、腹股沟白色脂肪组织(iWAT)、附睾白色脂肪组织(eWAT)、棕色脂肪组织(BAT)的重量和大小以及UCP1表达,同时评估肝脏脂肪沉积和形态。

结果

与对照组相比,尼古丁给药降低了体重,并减小了iWAT和eWAT的重量和大小。尼古丁给药频率对体重和脂肪组织的影响比剂量本身更显著,2毫克/千克bid是减轻体重的最佳剂量。尼古丁增加了BAT细胞数量,并增强了iWAT和BAT中UCP1的表达。它对eWAT UCP1表达影响较小,对肝脏脂肪沉积或形态没有实质性影响,除了剂量超过4毫克/千克时肝脏重量减轻。

结论

尼古丁诱导的体重减轻与给药频率有关,2毫克/千克bid是最佳方案。其机制可能包括iWAT和eWAT重量及细胞大小的减少、iWAT的褐变诱导、BAT数量增加和UCP1表达增强,以及iWAT和BAT中能量消耗增加。尼古丁诱导eWAT褐变的能力相对较弱,表明其在不同脂肪组织类型中的作用机制不同。这些发现为进一步探索尼古丁的多方面功能及其潜在机制提供了基础。

意义

本研究考察了不同尼古丁剂量和给药频率如何影响小鼠体重和脂肪组织。研究发现,以2毫克/千克bid(每日两次)给药尼古丁可实现最佳体重减轻。尼古丁诱导白色脂肪组织褐变,增加BAT数量和UCP1表达,并影响能量消耗。这些发现强调了尼古丁在不同脂肪组织类型中的细微影响,并为进一步探索其在体重管理中的机制和治疗潜力奠定了基础。

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