Improvement Of Lactobacillus Paracasei Jlus66 On Glucose And Lipid Metabolism Disorders And Cognitive Impairment In Obese Mice

In recent years,obesity and its complications caused by high-energy dietary patterns represented by high-fat diet(HFD)have become a world public health problem.Studies have shown that long-term HFD can lead to glycolipid metabolism disorder,affecting the normal operation of organs such as the liver and intestines,as well as damaging the brain and nervous system,eventually leading to cognitive impairment.The gut microbiota,as an environmental factor,influences systemic metabolism by affecting energy balance,inflammation,and gut barrier function,integrating peripheral and central food intake regulatory signals,resulting in weight loss.Probiotics affect food intake,body weight,and systemic metabolic function primarily by modulating gut microbiota.In this paper,L.paracasei Jlus66 isolated from natural fermented milk was used as the research object to study the improvement effect of L.paracasei Jlus66 on HFD-induced glycolipid metabolism disorder and cognitive impairment in mice through in vivo experiments.The main research contents and results are as follows:(1)Interventional effect of Jlus66 on HFD-induced obesity in mice.HFD-induced obesity and high-fat model in mice,and Jlus66 was used to intervene.The results showed that Jlus66 significantly attenuated HFD-induced obesity(p <0.01)and fat accumulation in mice,significantly decreased serum TG levels(p <0.05),and increased HDL-C levels(p < 0.01).(2)Interventional effect of Jlus66 on HFD-induced cognitive impairment in mice.The results of the water maze experiment showed that compared with the mice in the HFD group,the mice in the Jlus66 group could quickly find the underwater platform(p < 0.05);Western blots and RT-q PCR results showed that Jlus66 significantly increased the expression of neurotrophic factors and synaptic proteins(BDNF,PSD95,SNAP25)and genes(bdnf,snap25,psd95)(p < 0.01),alleviating the effects of HFD feeding memory impairment;regulated the expression of insulin-related proteins(IRS,AKT,GSK,GLUT4,PTP1B)and alleviated insulin resistance(p < 0.05 or p < 0.01);the expression of neuroinflammatory proteins(JNK,p38)and genes(Inos,Cox-2,Il-6)was decreased,and neuroinflammation was attenuated(p < 0.05 or p < 0.01).(3)Interventional effect of Jlus66 on HFD-induced disturbance of hepatic glucose and lipid metabolism in mice.The results showed that Jlus66 attenuated the HFD-induced increase in liver weight(p < 0.01)and the accumulation of fat vacuoles in mice;reduced the levels of TC,TG and LDL-C in the liver(p < 0.01)and increased the level of HDL-C(p < 0.01);Western blots and RT-q PCR results showed that Jlus66 improved the expression of insulin resistance protein and alleviated insulin resistance in the liver(p < 0.05 or p < 0.01);inhibited the expression of inflammatory proteins(p< 0.05),attenuated the inflammatory response of the liver;promoted the expression of mitochondrial genes(Cox5b,Sirt1,Cox7a1,Cox II,Cox8 b and Cycs)(p < 0.01),and attenuated liver mitochondrial dysfunction.(4)Interventional effects of Jlus66 on HFD-induced disturbances of intestinal and fat metabolism in mice.The results showed that Jlus66 reduced intestinal lipid accumulation,increased the expression of tight junction proteins(Zo-1,Claudin-1 and Occludin)(p < 0.01),protected the integrity of the jejunal barrier;reduced the expression of inflammatory and oxidative stress proteins and genes,and attenuated inflammation and oxidative stress in the jejunum.Meanwhile,Jlus66down-regulated the expression of fat accumulation genes(Fas,Acaca,Pparg,Ppara,Srebp1 c and Cidea)and inflammatory genes(Inos,Cox-2,Tnf-?,Il-1? and Il-6)(p <0.05 or p < 0.01),up-regulated the expression of thermogenic genes(Ucp1,Ucp4,Ucp5,Pgc1?,Prdm16 and Ebf2),mitochondrial genes,and autophagy genes(Atg3,Atg5,Atg7,Atg14,Lc3 and p62)(p < 0.05)or p < 0.01),alleviated the metabolic disturbance of adipose tissue caused by HFD.In summary,Jlus66 ameliorated HFD-induced glucose and lipid metabolism disorders and cognitive impairment by improving the expression of neurotrophic factors and synapse-related proteins and genes in the brain,as well as regulating insulin resistance and inflammatory responses in the liver and gut.This study lays a theoretical foundation for the development and utilization of probiotics in the field of health care and medicine.