| Objective: The underlying mechanisms of lipid metabolism abnormalities related to obesity remain unclear.In recent years,numerous studies have indicated a close relationship between micro RNAs and lipid metabolism,among which micro RNA-155(mi R-155)in the liver may play a crucial regulatory role in obesity-related lipid metabolism abnormalities.However,the specific mechanisms need to be further investigated.Literature review suggests that mi R-155 may inhibit the expression of liver X receptor alpha(LXRα),a key regulator of essential lipid homeostasis,leading to a significant increase in the expression of sterol regulatory element-binding protein 1(SREBP-1).This,in turn,promotes the synthesis of fatty acid synthase(FAS),thereby enhancing lipid synthesis metabolism in the liver,resulting in increased lipid synthesis and abnormal lipid metabolism.Additionally,the elevated levels of mi R-155 in the liver may also affect the secretion of tumor necrosis factor alpha(TNFα)by regulating peroxisome proliferator-activated receptor gamma(PPARγ),thereby influencing the synthesis of peroxisome proliferator-activated receptor gamma coactivator 1 alpha(PGC1-α),and ultimately leading to a decrease in the content of carnitine palmitoyltransferase 1(CPT-1).This,in turn,exacerbates hepatic lipid accumulation.Studies have indicated that obesity starting early in life may pose greater risks for adulthood diseases.Therefore,this study aims to establish a mouse model of early-onset obesity and investigate the role of liver mi R-155 in obesity-related lipid metabolism abnormalities,as well as the potential regulatory pathways involved in lipid metabolism,providing a theoretical basis for the mechanistic research of obesity-related lipid metabolism.Methods: Forty-eight offspring mice,including 24 males and 24 females,from 12 pairs of C57BL/6J mice were randomly selected and housed in pairs after 7 days of adaptive feeding.The male and female offspring mice were divided into high-fat diet(HFD)group and control group(CON),with 12 mice in each group.The HFD group was fed a60% high-fat diet during lactation for 21 days and continued to receive the same diet after weaning until sacrificed at 12 weeks old.The CON group was fed a regular diet.After 12 weeks of feeding,the mice were sacrificed and the liver tissue was stained with HE and oil red O for pathological examination.Blood and liver tissue were used for biochemical analysis of levels of total cholesterol(TC),triglycerides(TG),low-density lipoprotein(LDL),and high-density lipoprotein(HDL)in both male and female mice.Western blot analysis was used to examine the protein expression levels of LXRα,SREBP-1,FAS,PPARγ,TNFα,PGC1-α,and CPT-1 in the liver.q RT-PCR was performed to measure the expression levels of mi R-155-5p,LXRα,SREBP-1,and FAS genes in the liver.This study established a mouse model of early-life obesity to investigate the role of liver mi R-155 in obesity-related lipid metabolism disorders and the possible regulatory pathways involved,providing a theoretical basis for the study of the mechanism of obesity-related lipid metabolism disorders.Results: 1.From weaning at 21 days to 12 weeks,the body weight of both male and female mice in the HFD group was significantly higher than that in the CON group(P<0.01).2.At the end of the 12-week experiment,the body fat,body fat percentage,and lean body weight of both male and female mice in the HFD group were significantly higher than those in the CON group(P<0.05).3.The perirenal fat weight and coefficient,as well as the gonadal fat weight and coefficient of both male and female mice in the HFD group,were significantly increased compared with those in the CON group(P<0.01).4.The liver histology of the CON group mice showed uniform hepatocyte size and morphology without fat accumulation-induced vacuoles.The HFD group mice exhibited severe hepatic steatosis with occasional hepatocyte atrophy.5.The liver histology of the CON group mice stained with Oil Red O showed no obvious lipid deposits,while the HFD group mice exhibited severe hepatic lipid deposition.6.From the21 st day of weaning until 12 weeks,the body weights of male and female mice in the HFD group were significantly higher than those in the CON group(P<0.01).At the end of the 12-week experiment,the HFD group showed significant increases in body fat mass,body fat percentage,and lean body mass compared to the CON group in both male and female mice(P<0.05).Furthermore,the perirenal and gonadal fat mass and coefficients in the HFD group were significantly higher than those in the CON group(P<0.01).7.The serum levels of TC,TG,and LDL in the male and female mice in the HFD group were significantly higher than those in the CON group(P<0.05),while the HDL levels were significantly lower than those in the CON group.The hepatic levels of TC and TG in the HFD group were significantly higher than those in the CON group in both male and female mice(P<0.05).The protein expression levels of LXRα and CPT-1 in the liver of male and female mice in the HFD group were significantly lower than those in the CON group(P<0.01),whereas the protein expression levels of SREBP-1,FAS,PPARγ,TNFα,and PGC1-αwere significantly higher than those in the CON group(P<0.01).8.The m RNA expression levels of mi R-155-5p,SREBP-1,and FAS in the liver of male and female mice in the HFD group were significantly higher than those in the CON group(P<0.05),whereas the m RNA expression level of LXRα was significantly lower than that in the CON group(P<0.05).Conclusion: 1.Lipid metabolism abnormalities in male and female mice with early-onset obesity were observed.2.Obesity-related lipid metabolism abnormalities may be associated with elevated expression of hepatic mi R-155-5p,affecting the LXRα/SREBP-1/FAS pathway and enhancing lipid synthesis metabolism,leading to elevated blood lipid levels.3.Obesity-related lipid metabolism abnormalities may be associated with elevated expression of hepatic mi R-155-5p,affecting the PPARγ/TNFα/PGC1-α/CPT-1 pathway and inhibiting lipid breakdown metabolism,resulting in elevated blood lipid levels. |
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