Study On Caffeine Intervention In Fatty Liver And Partial Substitution Of Nicotine In Anti-Withdrawal

Modern diets are developing towards a high-fat pattern which contains refined sugar and saturated fatty acids.The risk of nonalcoholic fatty liver disease（NAFLD）with histological characteristics of liver steatosis increases with the widespread of high-fat diet（HFD）pattern.Nicotine is the main psychoactive substance that causes tobacco addiction.Nicotine exposure under a high-fat diet will aggravate the degree of intrahepatic steatosis and lead to the development of fatty liver to liver fibrosis.E-cigarettes are one of the most popular forms of nicotine delivery,which have adjustable composition with the addition of bioactive substances.According to the latest regulations,only coffee and cocoa extracts can be added into the e-cigarettes,except essences and spices for tobacco.Caffeine has lower addiction compared to nicotine and has physiological functions of refreshing,anti-fatigue and promoting fat metabolism.In this paper,we first explored the intervention effect of caffeine on the liver steatosis of nicotine ingested mice under HFD,aiming at the liver fat metabolism disorder of smokers under HFD.Besides,the effects of partially replacing nicotine by caffeine on nicotine withdrawal symptoms on mice was also investigated.Additionally,using electronic cigarettes as the application carrier,we prepared the coffee extract for electronic cigarettes with propylene glycol as the solvent.The detailed contents and results of this research are listed below:（1）The intervention effect of caffeine on liver fat metabolism in mice with nicotine intake on a high-fat diet was studied.The results showed that both HFD and nicotine were high risk factors for NAFLD,and nicotine could aggravate steatosis caused by HFD,leading to further deterioration of NAFLD.Caffeine intervention could not only effectively inhibit the weight growth of nicotine ingested mice under HFD,reduce visceral fat,but also reduced the content of TG,T-CHO and LDL-C in blood,increased the content of HDL-C.It also reduced liver oxidative stress and hepatocyte damage,promoted the expression of fat oxidative decomposition genes and inhibited the expression of fat synthesis genes,and improved steatosis in the liver.（2）The effects of partial replacement of nicotine by caffeine on nicotine withdrawal symptoms in mice were explored,through animal ethology and brain dopamine determination.The results showed that partial substitution of nicotine with caffeine effectively reduced the symptoms of nicotine withdrawal,increased the motor activity and pain threshold of mice during withdrawal,reduced their anxiety and depressive behaviors,and improved their memory and cognitive abilities,increased dopamine levels in VTA and PFC.（3）The coffee extract was developed for e-cigarettes as the suitable application vectors.The process was optimized,and the in vitro antioxidant activity and flavor were measured The results showed that the optimal extraction conditions were propylene glycol concentration of75%,liquid to material ratio of 15:1,reflux time of 87 min,reflux temperature of 100℃,ultrasound power of 200 W,and ultrasound time of 5 min.Under these conditions,the highest caffeine extraction amount（9.28 mg/g coffee powder）was obtained.Antioxidant analysis in vitro showed that the DPPH free radical scavenging ability of the coffee extract was 12.99 m M Trolox/m L,and its iron ion reduction ability was 34.04 m M Fe SO₄/m L,which showed stronger overall antioxidant activity compared to traditional water extracts.GC-MS showed that the extract contains 26 volatile flavor components,exhibiting the characteristic aroma of coffee.