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

Abstract Introduction This study investigates the effects of varying nicotine doses and administration frequencies on mouse body weight, adipose tissues, and liver. Methods Male C57BL6/J mice received subcutaneous nicotine doses (0.5mg/kg, 1mg/kg, or 2mg/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 2mg/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 4mg/kg. Conclusions Nicotine-induced weight reduction is frequency-dependent, with 2mg/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 2mg/kg leads to optimal weight reduction. Nicotine induces browning in white adipose tissue, increases brown adipose tissue quantity and UCP1 expression, and affects energy expenditure. The findings underscore nicotine's nuanced effects across different adipose tissue types and lay groundwork for further exploration of its mechanisms and therapeutic potential in weight management.