AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease(NAFLD) and the related underlying mechanism.METHODS: After 9 d of acclimation to a constant temperature-controlled room(...AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease(NAFLD) and the related underlying mechanism.METHODS: After 9 d of acclimation to a constant temperature-controlled room(20 ℃-22 ℃) under 12h light/dark cycles,male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet(n = 8) or a high-fat diet(HFD)(n = 32) for 10 d.Animals receiving HFD were then randomly divided into 4 groups and administered with 0,12.5,25,or 50 mg/kg(body weight) per day of lutein for the next 45 d.At the end of the experiment,the perinephric and abdominal adipose tissues of the rats were isolated and weighed.Additionally,serum and liver lipid metabolic condition parameters were measured,and liver function and insulin resistance state indexes were assessed.Liver samples were collected and stained with hematoxylin eosin and Oil Red O,and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses.RESULTS: Our data showed that after being fed a high-fat diet for 10 d,the rats showed a significant gain in body weight,energy efficiency,and serum total cholesterol(TC) and triglyceride(TG) levels.Lutein supplementation induced fat loss in rats fed a highfat diet,without influencing body weight or energy efficiency,and decreased serum TC and hepatic TC and TG levels.Moreover,lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content,and also improved insulin sensitivity.Lutein administration also increased the expression of key factors in hepatic insulin signaling,such as insulin receptor substrate-2,phosphatidylinositol 3-kinase,and glucose transporter-2 at the gene and protein levels.Furthermore,high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1,which are associated with lipid metabolism and insulin signaling.CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.展开更多
Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear...Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.展开更多
基金Supported by Grants from the National High Technology Research and Development Program of China,No.2010AA023003the National Natural Science Foundation of China,No.NSFC-81172657
文摘AIM: To investigate the therapeutic effects of lutein against non-alcoholic fatty liver disease(NAFLD) and the related underlying mechanism.METHODS: After 9 d of acclimation to a constant temperature-controlled room(20 ℃-22 ℃) under 12h light/dark cycles,male Sprague-Darley rats were randomly divided into two groups and fed a standard commercial diet(n = 8) or a high-fat diet(HFD)(n = 32) for 10 d.Animals receiving HFD were then randomly divided into 4 groups and administered with 0,12.5,25,or 50 mg/kg(body weight) per day of lutein for the next 45 d.At the end of the experiment,the perinephric and abdominal adipose tissues of the rats were isolated and weighed.Additionally,serum and liver lipid metabolic condition parameters were measured,and liver function and insulin resistance state indexes were assessed.Liver samples were collected and stained with hematoxylin eosin and Oil Red O,and the expression of the key factors related to insulin signaling and lipid metabolism in the liver were detected using Western blot and real-time polymerase chain reaction analyses.RESULTS: Our data showed that after being fed a high-fat diet for 10 d,the rats showed a significant gain in body weight,energy efficiency,and serum total cholesterol(TC) and triglyceride(TG) levels.Lutein supplementation induced fat loss in rats fed a highfat diet,without influencing body weight or energy efficiency,and decreased serum TC and hepatic TC and TG levels.Moreover,lutein supplementation decreased hepatic levels of lipid accumulation and glutamic pyruvic transaminase content,and also improved insulin sensitivity.Lutein administration also increased the expression of key factors in hepatic insulin signaling,such as insulin receptor substrate-2,phosphatidylinositol 3-kinase,and glucose transporter-2 at the gene and protein levels.Furthermore,high-dose lutein increased the expression of peroxisome proliferators activated receptor-α and sirtuin 1,which are associated with lipid metabolism and insulin signaling.CONCLUSION: These results demonstrate that lutein has positive effects on NAFLD via the modulation of hepatic lipid accumulation and insulin resistance.
基金supported by grants to Chunyu Zeng from the Program of Innovative Research Team by National Natural Science Foundation(81721001,China)National Natural Science Foundation of China(31430043,31730043)+5 种基金Program for Changjiang Scholars,and Innovative Research Team in University(IRT1216,China)the National Key R&D Program of China(2018YFC1312700)by grant to Jingwen Guo from the National Natural Science Foundation of China(82000476)by grant to Yijie Hu from the Excellent Talents Project of Third Military Medical University(B-3232,China)by grant to Hongyong Wang from the Clinical Technology Innovation and Cultivation Program of AMU(CX2019JS220,China)by grant to Xinyue Li from Chongqing Natural Science Foundation(CSTB2022NSCQ-BHX0025,China)。
文摘Myocardial dysfunction is the most serious complication of sepsis.Sepsis-induced myocardial dysfunction(SMD)is often associated with gastrointestinal dysfunction,but its pathophysiological significance remains unclear.The present study found that patients with SMD had higher plasma gastrin concentrations than those without SMD.In mice,knockdown of the gastrin receptor,cholecystokinin B receptor(Cckbr),aggravated lipopolysaccharide(LPS)-induced cardiac dysfunction and increased inflammation in the heart,whereas the intravenous administration of gastrin ameliorated SMD and cardiac injury.Macrophage infiltration plays a significant role in SMD because depletion of macrophages by the intravenous injection of clodronate liposomes,48 h prior to LPS administration,alleviated LPSinduced cardiac injury in Cckbr-deficient mice.The intravenous injection of bone marrow macrophages(BMMs)overexpressing Cckbr reduced LPS-induced myocardial dysfunction.Furthermore,gastrin treatment inhibited toll-like receptor 4(TLR4)expression through the peroxisome proliferator-activated receptor a(PPAR-a)signaling pathway in BMMs.Thus,our findings provide insights into the mechanism of the protective role of gastrin/CCKBR in SMD,which could be used to develop new treatment modalities for SMD.
