Effects Of Different Protein Levels On Glucose And Lipid Metabolism In Overweight/Obese Rats Under Limited Energy

Objective:To study the effects of different protein levels on glucose and lipid metabolism in overweight/obese rats under energy-limited conditions,and analyze the multiple regulation and connection between various signaling pathways of glucose and lipid metabolism;Discuss the regulation mechanism of different protein intake on the body's glucose and lipid metabolism while reducing the energy intake of overweight/obese rats,providing a theoretical basis for reasonable weight loss.Method:72 SD rats(half male and half female)were randomly selected after one week of adaptive feeding.6 rats were fed with normal diet as normal control group(NC),and the rest were fed with high-fat diet.After 9 weeks,the rats were randomly divided into model control group(MC),low energy and low protein group(LP),low energy and normal protein group(NP)and low energy and high protein group(HP)according to their body weight.Then they were intervened with energy and protein intake for 9 weeks,and their body weight and food intake were measured every weekend.After the intervention,the mice were weighed and killed,and the serum,adipose tissue(periepididymal,subcutaneous,retroperitoneal and interscapular)and liver tissue were collected.(1)Detect blood glucose,blood lipids,insulin(INS),glucagon(GC),adiponectin(APN),leptin(LEP)content;(2)Detect liver fat content and signals related to liver lipid metabolism factor content:?fat synthesis-related signal pathway factors:adenylate activated protein kinase(AMPK),carbohydrate response element binding protein(ChREBP),sterol regulatory element protein 1c(SREBP-1c),acetyl-Coenzyme A carboxylase(ACC),fatty acid synthase(FAS);?signal factors related to fatty acid oxidation:peroxisome proliferator activated receptor a(PPAR?),carnitine palmitoyl transferase-1(CPT-1);?cholesterol synthesis related signal factors:sterol regulatory element binding protein 2(SREBP-2),3-hydroxy-3-methylglutaryl coenzyme A(HMGCOA),low-density lipoprotein receptor(LDL-R);?cholesterol decomposition related signal factors:peroxisome proliferator activated receptor ?(PPAR?),cholesterol 7?-hydroxylase(CYP7A1);(3)Detection of signal factor content in pathways related to liver glucose metabolism:?gluconeogenesis related signals pathway factors:Silent Information Regulator 1(SIRT1),Peroxisome Proliferator Activated Receptor ? Coactivator 1?(PGC-1?),Forkhead Box Protein O1(FoxO1);?signal pathways related to glycogen synthesis factors:insulin receptor substrate 2(IRS2),phosphoinositide 3-kinase(PI3K),protein kinase B(AKT),glycogen synthase kinase-3 ?(GSK3)Results:1.Food intake,body weight and body fat of rats:(1)After energy limitation,the daily food intake,energy and fat intake of rats were significantly lower than those in the MC group(P<0.05);among the 3 intervention groups,protein intake showed an upward trend,while carbohydrates decreased are significant differences in trends(P<0.05),but no gender difference in this trend.(2)After energy limitation,the body weight of rats was significantly lower than the NC group and MC group(P<0.05);among the 3 intervention groups,the weight of the rats in the HP group was the lightest,but there was no significant difference.and all the trends were no gender difference(3)After energy limitation,the white fat and brown fat mass of rats were significantly lower than the MC group(P<0.05);among the 3 intervention groups,there was no significant difference in fat mass in each group,and all the trends were no gender difference.2.Effects of different protein levels on blood glucose,blood lipids and related hormones in overweight/obese rats under energy-limited state:(1)After energy limitation,the content of TG in both male and female rats was significantly lower than the MC group(P<0.05),and HDL-C was significantly higher than the MC group(P<0.05);among the 3 intervention groups,the contents of male rats were no significant difference in indicators.The contents of TC and VLDL-C in the HP group of female rats were significantly lower than those in the LP and NP groups(P<0.05).(2)After energy limitation,the contents of GLU and GC in male rats were significantly lower than those in the MC group(P<0.05).There was no significant difference in the contents of GLU and GC among the 3 intervention groups.The contents of INS in the NP and HP groups were significantly higher than those in the LP group(P<0.05),there was no significant difference in GLU content between the intervention group of female rats and the MC group(P<0.05).The INS change trend of the 3 intervention groups was the same as male rats.With increasing of protein intake,the GC content showed an upward trend.3.Effects of different protein levels on liver lipid metabolism in overweight/obese rats under energy-limited state:(1)After energy limitation,the liver weight and liver fat weight of male and female rats were significantly lower than the MC group(P<0.05);there was no significant difference in liver weight between the 3 intervention groups(P<0.05),and the weight of liver fat of male rats in the HP group was significantly lower than that in the LP group and NP group(P<0.05),but there was no significant difference in female mice.(2)After energy limitation,the APN content of both male and female rats was significantly higher than the MC group(P<0.05),and the LEP content was significantly lower than the MC group(P<0.05);among the 3 intervention groups of male rats,the content of APN and LEP in NP group was significantly higher than the LP group(P<0.05).With the increasing of protein intake,the content of APN and LEP showed an upward trend.However,there was no significant difference between the 3 intervention groups of female rats.(3)Pathways related to fat synthesis:After energy limitation,the contents of AMPK in the 3 intervention groups of male rats increased but there was no significant difference,and the contents of ChREBP,ACC,and FAS were significantly decreased(P<0.05).The LP and NP groups the content of SREBP-lc was significantly reduced(P<0.05).The content of SREBP-1c in the HP group was reduced but there was no significant difference.The content of AMPK in the 3 intervention groups of female rats was significantly increased(P<0.05),ChREBP,SREBP-lc,The contents of ACC and FAS were significantly reduced(P<0.05);among the 3 intervention groups,the contents of SREBP-1c and FAS in the HP group of male rats were significantly higher than those in the LP and NP groups,and the content of ChREBP was significantly lower than that in the LP and NP groups(P<0.05),and there was no significant difference in other indicators.The contents of ChREBP and ACC in the HP group of female rats were significantly lower than those in the LP and NP groups(P<0.05),and there were no significant differences in other indicators.(4)Pathways related to fatty acid oxidation:After energy limitation,the contents of PPAR? and CPT1 in rats were significantly higher than those in the MC group(P<0.05);among the 3 intervention groups,with the increase in protein intake,rats PPARa and CPT1 The content showed an upward trend,and the content of PPAR? in the HP group was significantly higher than that in the LP and NP groups(P<0.05),and there was no gender difference in this trend(5)Pathways related to cholesterol synthesis:After energy limitation,the contents of SREBP-2,HMG-COA,and LDL-R in rats were significantly higher than those in the MC group(P<0.05);among the 3 intervention groups,the amount of protein intake the content of SREBP-2,HMG-COA,and LDL-R in the HP group of the 3 intervention groups was the lowest,and there was no gender difference in this trend.(6)Pathways related to cholesterol decomposition:After energy limitation,the levels of PPARa and CYP7A1 in rats were significantly higher than those in the MC group(P<0.05);among the 3 intervention groups,with the increase in protein intake,the HP of the 3 intervention groups the content of PPAR? and CYP7A1 was the highest in the group,and there was no gender difference in this trend4.Effects of different protein levels on liver glucose metabolism in overweight/obese rats under energy-limited state:(1)Pathways related to glycogen synthesis:After energy limitation,the contents of IRS2,PI3K,and AKT in rats were significantly higher than those in the MC group(P<0.05),and the contents of GSK3 were significantly lower than those in the MC group(P<0.05);3 interventions Among the groups,the content of IRS2,PI3K,and AKT in the NP group was the highest,and the content of GSK3 was the lowest,and there was no gender difference in this trend.(2)Pathways related to gluconeogenesis:After energy limitation,the levels of SIRT1 and PGC-1? in rats were significantly higher than those in the MC group(P<0.05),and the content of FoxO1 was significantly lower than that in the MC group(P<0.05);3 interventions among the groups,the content of SIRT1 in the NP group was significantly higher than the LP group(P<0.05),and the content of PGC-1? was significantly higher than the LP and HP groups(P<0.05),and there was no gender difference in this trend.Conclusion:Energy limitation can reduce the expression of signal factors related to fat synthesis and cholesterol synthesis by promoting the expression of signal factors related to fat oxidation and cholesterol decomposition in the liver;at the same time,it can promote the expression of signal factors related to glycogen synthesis in the liver and reduce the expression of signal factors related to gluconeogenesis,thereby significantly reducing the weight,body fat and liver fat mass of overweight/obese rats,and improving blood sugar and blood lipids.Increasing the protein energy ratio of the energy-restricted diet to twice the normal intake can promote the expression of signal factors related to fat oxidation and cholesterol decomposition in the liver,and reduce the expression of signal factors related to cholesterol synthesis,thereby improving the body weight and body fat,blood lipid and blood cholesterol of rats,and the effect has gender differences,respectively,the effect of reducing the liver fat of male rats is stronger but the blood cholesterol is just the opposite.