Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseas...Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.展开更多
Background:Early-weaning of piglets is often accompanied by severe disorders,especially diarrhea.The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeosta...Background:Early-weaning of piglets is often accompanied by severe disorders,especially diarrhea.The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host.Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets.However,the metabolic response to L.frumenti administration remains unclear.Then,we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L.frumenti or phosphatebuffered saline(PBS).Results:A total of 1006-day-old crossbred piglets(Landrace×Yorkshire)were randomly divided into two groups and piglets received PBS(sterile,2 m L)or L.frumenti(suspension in PBS,10~8 CFU/m L,2 m L)by oral administration once per day from 6 to 20 days of age.Piglets were weaned at 21 days of age.Serum and liver samples for metabolomic analyses were collected at 26 days of age.Principal components analysis(PCA)showed that L.frumenti altered metabolism in serum and liver.Numerous correlations(P<0.05)were identified among the serum and liver metabolites that were affected by L.frumenti.Concentrations of guanosine monophosphate(GMP),inosine monophosphate(IMP),and uric acid were higher in serum of L.frumenti administration piglets.Pathway analysis indicated that L.frumenti regulated fatty acid and amino acid metabolism in serum and liver.Concentrations of fatty acidβ-oxidation related metabolites in serum(such as3-hydroxybutyrylcarnitine,C4-OH)and liver(such as acetylcarnitine)were increased after L.frumenti administration.Conclusions:Our findings suggest that L.frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets,where it promotes fatty acidβ-oxidation and energy production.High serum concentrations of nucleotide intermediates,which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets,were further detected.These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.展开更多
Low-temperature storage is convenient for postharvest preservation of peach fruit,but peach fruit is sensitive to cold damage,which lowers its quality.Nitric oxide(NO)has the potential to improve the bitter resistance...Low-temperature storage is convenient for postharvest preservation of peach fruit,but peach fruit is sensitive to cold damage,which lowers its quality.Nitric oxide(NO)has the potential to improve the bitter resistance of peach fruit.In this work,peach fruit was treated with 15μmol L^(−1)NO and 5μmol L^(−1)c-PTIO[2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxo-3-oxide],to study changes in mitochondrial fatty acids and expression of the C-repeat binding factor(CBF).The results showed that 15μmol L^(−1)exogenous NO significantly maintained fruit quality,reduced peroxidation of mitochondrial fatty acids,increased the activities of the antioxidants superoxide dismutase(SOD),peroxidase(POD),catalase(CAT),ascorbic acid peroxidase(APX),and reduced the content of hydrogen peroxide(H_(2)O_(2)).Meanwhile,NO treatment suppressed the increase in browning index and ion leakage rate,increased the activity of S-nitrosoglutathione reductase(GSNOR),the contents of S-nitrosothiols(SNOs),and the ratios of mitochondrial NAD^(+)/NADH and NADP^(+)/NADPH,increased the expression levels of PpCBF1/5/6.However,the expression levels of PpCBF2/3/4 were not significantly regulated by exogenous NO.Peaches treated with c-PTIO showed opposite effects to those treated with exogenous NO.These results suggest that exogenous NO can improve antioxidant capacity,preserve mitochondrial fatty acids,and upregulate the expression of PpCBF1/5/6 to alleviate cold tolerance and maintain the peach quality during storage.展开更多
BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in...BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown. A high ratio may promote lipogenic pathways and contribute to reactive oxygen species(ROS)-mediated damage, perhaps leading to mitochondrial dysfunction.Therefore, these parameters were investigated to understand their contribution to NAFLD development.AIM To examine the effect of increasing ratios of omega-6:3 fatty acids on mitochondrial function and lipid metabolism mediators.METHODS Hep G2-derived VL-17 A cells were treated with normal(1:1, 4:1) and high(15:1,25:1) ratios of omega-6: omega-3 fatty acids [arachidonic acid(AA):docosahexaenoic acid(DHA)] at various time points. Mitochondrial activity and function were examined via MTT assay and Seahorse XF24 analyzer, respectively.Triglyceride accumulation was determined by using Enzy Chrom? and levels of ROS were measured by fluorescence intensity. Protein expression of the mediators of lipogenic, lipolytic and endocannabinoid pathways was assessed by Western blotting.RESULTS High AA:DHA ratio decreased mitochondrial activity(P < 0.01;up to 80%) and promoted intracellular triglyceride accumulation(P < 0.05;40%-70%).Mechanistically, it altered the mediators of lipid metabolism;increased the expression of stearoyl-Co A desaturase(P < 0.05;22%-35%), decreased the expression of peroxisome proliferator-activated receptor-alpha(P < 0.05;30%-40%) and increased the expression of cannabinoid receptor 1(P < 0.05;31%).Furthermore, the high ratio increased ROS production(P < 0.01;74%-115%) and reduced mitochondrial respiratory functions such as basal and maximal respiration, ATP production, spare respiratory capacity and proton leak(P < 0.01;35%-68%).CONCLUSION High AA:DHA ratio induced triglyceride accumulation, increased oxidative stress and disrupted mitochondrial functions. Stimulation of lipogenic and steroidal transcription factors may partly mediate these effects and contribute to NAFLD development.展开更多
Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious i...Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious illness. In this editorial, we review the recent advances in understanding the pathogenesis of AFLP and discuss the studies documenting a fetal-maternal interaction with a causative association between carrying a fetus with a defect in mitochondrial fatty acid oxidation and development of AFLP. Further, we discuss the impact of these recent advances on the offspring born to women who develop AFLP, such that screening for a genetic defect can be life saving to the newborn and would allow genetic counseling in subsequent pregnancies. The molecular basis and underlying mechanism for this unique fetal-maternal interaction causing maternal liver disease is discussed.展开更多
E3 ligases are key enzymes required for protein degradation.Here,we identified a C3H2C3 RING domaincontaining E3 ubiquitin ligase gene named GhATL68b.It is preferentially and highly expressed in developing cotton fib...E3 ligases are key enzymes required for protein degradation.Here,we identified a C3H2C3 RING domaincontaining E3 ubiquitin ligase gene named GhATL68b.It is preferentially and highly expressed in developing cotton fiber cells and shows greater conservation in plants than in animals or archaea.The four orthologous copies of this gene in various diploid cottons and eight in the allotetraploid G.hirsutum were found to have originated from a single common ancestor that can be traced back to Chlamydomonas reinhardtii at about 992 million years ago.Structural variations in the GhATL68b promoter regions of G.hirsutum,G.herbaceum,G.arboreum,and G.raimondii are correlated with significantly different methylation patterns.Homozygous CRISPR-Cas9 knockout cotton lines exhibit significant reductions in fiber quality traits,including upper-half mean length,elongation at break,uniformity,and mature fiber weight.In vitro ubiquitination and cell-free protein degradation assays revealed that GhATL68b modulates the homeostasis of 2,4-dienoyl-CoA reductase,a rate-limiting enzyme for theβ-oxidation of polyunsaturated fatty acids(PUFAs),via the ubiquitin proteasome pathway.Fiber cells harvested from these knockout mutants contain significantly lower levels of PUFAs important for production of glycerophospholipids and regulation of plasma membrane fluidity.The fiber growth defects of the mutant can be fully rescued by the addition of linolenic acid(C18:3),the most abundant type of PUFA,to the ovule culture medium.This experimentally characterized C3H2C3 type E3 ubiquitin ligase involved in regulating fiber cell elongation may provide us with a new genetic target for improved cotton lint production.展开更多
“Crossover”概念可以解释耐力项目运动中,运动强度和耐力训练对糖、脂肪代谢平衡的影响。根据“Crossover”的概念:耐力训练引起肌肉的生化适应,增加脂肪的氧化供能。小强度运动(≤45% VO2 m ax)以脂肪供能为主,大强度运动(～75% VO2 ...“Crossover”概念可以解释耐力项目运动中,运动强度和耐力训练对糖、脂肪代谢平衡的影响。根据“Crossover”的概念:耐力训练引起肌肉的生化适应,增加脂肪的氧化供能。小强度运动(≤45% VO2 m ax)以脂肪供能为主,大强度运动(～75% VO2 m ax)糖是主要供能底物,即便是经过耐力训练也不例外。展开更多
基金Supported by the National Natural Science Foundation of China,No.81873915 and No.31872738the Key Plan of Nantong S&T Development,No.MS12020021the S&T Program of Medical School of Nantong University,No.TDYX2021010.
文摘Nonalcoholic fatty liver disease(NAFLD)or metabolic-associated fatty liver disease has been characterized by the lipid accumulation with injury of hepatocytes and has become one of the most common chronic liver diseases in the world.The complex mechanisms of NAFLD formation are still under identification.Carnitine palmitoyltransferase-Ⅱ(CPT-Ⅱ)on inner mitochondrial membrane(IMM)regulates long chain fatty acidβ-oxidation,and its abnormality has had more and more attention paid to it by basic and clinical research in NAFLD.The sequences of its peptide chain and DNA nucleotides have been identified,and the catalytic activity of CPT-Ⅱ is affected on its gene mutations,deficiency,enzymatic thermal instability,circulating carnitine level and so on.Recently,the CPT-Ⅱ dysfunction has been discovered in models of liver lipid accumulation.Meanwhile,the malignant transformation of hepatocyte-related CD44^(+) stem T cell activation,high levels of tumor-related biomarkers(AFP,GPC3)and abnormal activation of Wnt3a expression as a key signal molecule of the Wnt/β-catenin pathway run parallel to the alterations of hepatocyte pathology.This review focuses on some of the progress of CPT-Ⅱ inactivity on IMM with liver fatty accumulation as a possible novel pathogenesis for NAFLD in hepatocarcinogenesis.
基金supported by the National Key Research and Development Program of China(2017YFD0500503 and 2018YFD0500404)the Natural Science Foundation of China(31730090)Hubei Provincial Natural Science Foundation of China(2018CFA020).
文摘Background:Early-weaning of piglets is often accompanied by severe disorders,especially diarrhea.The gut microbiota and its metabolites play a critical role in the maintenance of the physiologic and metabolic homeostasis of the host.Our previous studies have demonstrated that oral administration of Lactobacillus frumenti improves epithelial barrier functions and confers diarrhea resistance in early-weaned piglets.However,the metabolic response to L.frumenti administration remains unclear.Then,we conducted simultaneous serum and hepatic metabolomic analyses in early-weaned piglets administered by L.frumenti or phosphatebuffered saline(PBS).Results:A total of 1006-day-old crossbred piglets(Landrace×Yorkshire)were randomly divided into two groups and piglets received PBS(sterile,2 m L)or L.frumenti(suspension in PBS,10~8 CFU/m L,2 m L)by oral administration once per day from 6 to 20 days of age.Piglets were weaned at 21 days of age.Serum and liver samples for metabolomic analyses were collected at 26 days of age.Principal components analysis(PCA)showed that L.frumenti altered metabolism in serum and liver.Numerous correlations(P<0.05)were identified among the serum and liver metabolites that were affected by L.frumenti.Concentrations of guanosine monophosphate(GMP),inosine monophosphate(IMP),and uric acid were higher in serum of L.frumenti administration piglets.Pathway analysis indicated that L.frumenti regulated fatty acid and amino acid metabolism in serum and liver.Concentrations of fatty acidβ-oxidation related metabolites in serum(such as3-hydroxybutyrylcarnitine,C4-OH)and liver(such as acetylcarnitine)were increased after L.frumenti administration.Conclusions:Our findings suggest that L.frumenti regulates lipid metabolism and amino acid metabolism in the liver of early-weaned piglets,where it promotes fatty acidβ-oxidation and energy production.High serum concentrations of nucleotide intermediates,which may be an alternative strategy to reduce the incidence of diarrhea in early-weaned piglets,were further detected.These findings broaden our understanding of the relationships between the gut microbiota and nutrient metabolism in the early-weaned piglets.
基金This work was supported by the National Natural Science Foundation of China(31800581 and 32071808).
文摘Low-temperature storage is convenient for postharvest preservation of peach fruit,but peach fruit is sensitive to cold damage,which lowers its quality.Nitric oxide(NO)has the potential to improve the bitter resistance of peach fruit.In this work,peach fruit was treated with 15μmol L^(−1)NO and 5μmol L^(−1)c-PTIO[2-(4-carboxyphenyl)-4,4,5,5-tetramethylimidazoline-1-oxo-3-oxide],to study changes in mitochondrial fatty acids and expression of the C-repeat binding factor(CBF).The results showed that 15μmol L^(−1)exogenous NO significantly maintained fruit quality,reduced peroxidation of mitochondrial fatty acids,increased the activities of the antioxidants superoxide dismutase(SOD),peroxidase(POD),catalase(CAT),ascorbic acid peroxidase(APX),and reduced the content of hydrogen peroxide(H_(2)O_(2)).Meanwhile,NO treatment suppressed the increase in browning index and ion leakage rate,increased the activity of S-nitrosoglutathione reductase(GSNOR),the contents of S-nitrosothiols(SNOs),and the ratios of mitochondrial NAD^(+)/NADH and NADP^(+)/NADPH,increased the expression levels of PpCBF1/5/6.However,the expression levels of PpCBF2/3/4 were not significantly regulated by exogenous NO.Peaches treated with c-PTIO showed opposite effects to those treated with exogenous NO.These results suggest that exogenous NO can improve antioxidant capacity,preserve mitochondrial fatty acids,and upregulate the expression of PpCBF1/5/6 to alleviate cold tolerance and maintain the peach quality during storage.
文摘BACKGROUND Non-alcoholic fatty liver disease(NAFLD) is a common cause of liver disease worldwide and is a growing epidemic. A high ratio of omega-6 fatty acids to omega-3 fatty acids in the diet has been implicated in the development of NAFLD. However, the inflicted cellular pathology remains unknown. A high ratio may promote lipogenic pathways and contribute to reactive oxygen species(ROS)-mediated damage, perhaps leading to mitochondrial dysfunction.Therefore, these parameters were investigated to understand their contribution to NAFLD development.AIM To examine the effect of increasing ratios of omega-6:3 fatty acids on mitochondrial function and lipid metabolism mediators.METHODS Hep G2-derived VL-17 A cells were treated with normal(1:1, 4:1) and high(15:1,25:1) ratios of omega-6: omega-3 fatty acids [arachidonic acid(AA):docosahexaenoic acid(DHA)] at various time points. Mitochondrial activity and function were examined via MTT assay and Seahorse XF24 analyzer, respectively.Triglyceride accumulation was determined by using Enzy Chrom? and levels of ROS were measured by fluorescence intensity. Protein expression of the mediators of lipogenic, lipolytic and endocannabinoid pathways was assessed by Western blotting.RESULTS High AA:DHA ratio decreased mitochondrial activity(P < 0.01;up to 80%) and promoted intracellular triglyceride accumulation(P < 0.05;40%-70%).Mechanistically, it altered the mediators of lipid metabolism;increased the expression of stearoyl-Co A desaturase(P < 0.05;22%-35%), decreased the expression of peroxisome proliferator-activated receptor-alpha(P < 0.05;30%-40%) and increased the expression of cannabinoid receptor 1(P < 0.05;31%).Furthermore, the high ratio increased ROS production(P < 0.01;74%-115%) and reduced mitochondrial respiratory functions such as basal and maximal respiration, ATP production, spare respiratory capacity and proton leak(P < 0.01;35%-68%).CONCLUSION High AA:DHA ratio induced triglyceride accumulation, increased oxidative stress and disrupted mitochondrial functions. Stimulation of lipogenic and steroidal transcription factors may partly mediate these effects and contribute to NAFLD development.
文摘Acute fatty liver of pregnancy (AFLP) is a serious maternal illness occurring in the third trimester of pregnancy with significant perinatal and maternal mortality. Till recently, it has been considered a mysterious illness. In this editorial, we review the recent advances in understanding the pathogenesis of AFLP and discuss the studies documenting a fetal-maternal interaction with a causative association between carrying a fetus with a defect in mitochondrial fatty acid oxidation and development of AFLP. Further, we discuss the impact of these recent advances on the offspring born to women who develop AFLP, such that screening for a genetic defect can be life saving to the newborn and would allow genetic counseling in subsequent pregnancies. The molecular basis and underlying mechanism for this unique fetal-maternal interaction causing maternal liver disease is discussed.
基金supported by the National Natural Science Foundation of China(31830057)the National Key R&D Program of China(2022YFF1001400)the Foundation of Hubei Hongshan Laboratory(2021hszd014).
文摘E3 ligases are key enzymes required for protein degradation.Here,we identified a C3H2C3 RING domaincontaining E3 ubiquitin ligase gene named GhATL68b.It is preferentially and highly expressed in developing cotton fiber cells and shows greater conservation in plants than in animals or archaea.The four orthologous copies of this gene in various diploid cottons and eight in the allotetraploid G.hirsutum were found to have originated from a single common ancestor that can be traced back to Chlamydomonas reinhardtii at about 992 million years ago.Structural variations in the GhATL68b promoter regions of G.hirsutum,G.herbaceum,G.arboreum,and G.raimondii are correlated with significantly different methylation patterns.Homozygous CRISPR-Cas9 knockout cotton lines exhibit significant reductions in fiber quality traits,including upper-half mean length,elongation at break,uniformity,and mature fiber weight.In vitro ubiquitination and cell-free protein degradation assays revealed that GhATL68b modulates the homeostasis of 2,4-dienoyl-CoA reductase,a rate-limiting enzyme for theβ-oxidation of polyunsaturated fatty acids(PUFAs),via the ubiquitin proteasome pathway.Fiber cells harvested from these knockout mutants contain significantly lower levels of PUFAs important for production of glycerophospholipids and regulation of plasma membrane fluidity.The fiber growth defects of the mutant can be fully rescued by the addition of linolenic acid(C18:3),the most abundant type of PUFA,to the ovule culture medium.This experimentally characterized C3H2C3 type E3 ubiquitin ligase involved in regulating fiber cell elongation may provide us with a new genetic target for improved cotton lint production.
文摘目的检测PTEN、CPT1A及COX4在高原鼠兔脂代谢相关组织中的表达水平,探讨其在能量代谢及环境适应过程中可能的作用。方法同一时间从青海门源地区捕捉20只高原鼠兔,运用western blotting法检测白色脂肪、棕色脂肪、肝脏、肌肉组织中PTEN、CPT1A及COX4蛋白的表达水平。结果 Western blotting显示,PTEN、CPT1A及COX4蛋白表达存在显著的组织水平差异。PTEN在肝脏高表达,而在棕色脂肪、白色脂肪和肌肉组织中表达相对较少(P=0.001);CPT1A与COX4在四种组织中的表达呈现一致的趋势,即在肝脏、肌肉、棕色脂肪组织中高表达,而在白色脂肪组织中表达很少甚至不表达(P<0.001)。结论 PTEN可能参与肝脏脂代谢过程。CPT1A主要参与脂肪酸β氧化,与肝脏脂肪酸氧化、骨骼肌能量摄取以及棕色脂肪产热供能有关。为高原鼠兔在高寒环境中生存提供能量。COX4作为线粒体氧化呼吸链末端的酶,促进线粒体氧化呼吸作用,通过肝脏脂肪酸氧化提供能量,促进骨骼肌能量摄取,并诱导棕色脂肪产热供能,进而调节机体能量代谢平衡。
文摘“Crossover”概念可以解释耐力项目运动中,运动强度和耐力训练对糖、脂肪代谢平衡的影响。根据“Crossover”的概念:耐力训练引起肌肉的生化适应,增加脂肪的氧化供能。小强度运动(≤45% VO2 m ax)以脂肪供能为主,大强度运动(～75% VO2 m ax)糖是主要供能底物,即便是经过耐力训练也不例外。
