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
The 13C-labeled fatty acids octanoic-1-13C acid and palmitic-1-13C acid were synthetically prepared from Ba 13CO3. The yield of the former was more than 90% and that of the latter was above 85%. MS, IR, 1H-NMR and 13N...The 13C-labeled fatty acids octanoic-1-13C acid and palmitic-1-13C acid were synthetically prepared from Ba 13CO3. The yield of the former was more than 90% and that of the latter was above 85%. MS, IR, 1H-NMR and 13NMR were performed to analyze the structures of the two 13C-fatty acids, compared with their unlabeled fatty acids.展开更多
Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity,...Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.MethodsA high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.ResultsThe expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.ConclusionsAdipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.展开更多
Particulate samples were collected from the Changjiang river system during a flood period, in May 1997, and POC, stable isotope and lipids associated with particles were examined. Results showed the decrease （0.84% ...Particulate samples were collected from the Changjiang river system during a flood period, in May 1997, and POC, stable isotope and lipids associated with particles were examined. Results showed the decrease （0.84% ～ 1.88%） of organic carbon content from the upper reaches to the estuary.δ^13 values of particulate organic carbon was in the range of -24.9×10^-3 to -26.6×10^-3, which were close to the isotopic signature of continental C3 vegetation. Total particulate n-alkanes concentrations varied from 1.4 to 10.1μg/dm^3,or from 23.7 to 107μg/g of total suspended matter. Fatty acids were present in all the samples, from 1.4 to 5.4μg/dm^3, with saturated and unsaturated straight-chain and branched compounds in the carbon number range from C12 to C30. Both δ^13 and the ratio of carbon content to nitrogen content indicate the predominance of terrestrial inputs （soil organic matter） among the particles. The biomarker approach has been used to identify the relative portion of terrigenous and autochthonous fraction in the particulate samples. The distribution of fatty acids suggests a striking phytoplanktonic and microbial signal in most particle samples. The terrestrial alkanes are used to estimate the contribution of terrestrial inputs along the mainstream.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 fibe...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
BACKGROUND Shifting on lifestyle,diet,and physical activity contributed on increasing number of obese people around the world.Multiple factors influence the development of obesity.Some research suggested that gut micr...BACKGROUND Shifting on lifestyle,diet,and physical activity contributed on increasing number of obese people around the world.Multiple factors influence the development of obesity.Some research suggested that gut microbiota(GM)plays an important role in nutrient absorption and energy regulation of individuals,thus affecting their nutritional status.Report of Indonesia Basic Health Research showed that the prevalence of obesity in every province tended to increase.Although the root cause of obesity is excessive calorie intake compared with expenditure,the differences in gut microbial ecology between healthy and obese humans may affect energy homeostasis.GM affect body weight,especially obesity.Probiotics that are consumed while alive and able to colonize in the intestine are expected to increase the population of good bacteria,especially Bifidobacteria and Lactobacilli,and suppress pathogens such as Enterobacteriaceae and Staphylococcus.The strain of L.plantarum Dad-13 has been demonstrated to survive and colonize in the gastrointestinal tract of healthy Indonesian adults who consume fermented milk containing L.plantarum Dad-13.The consumption of probiotic L.plantarum Dad-13 powder decreased E.coli and non-E.coli coliform bacteria in school-aged children in Indonesia.L.plantarum is a dominant bacterium in the average Indonesian’s GM.For this reason,this bacterium is probably a more suitable probiotic for Indonesians.AIM To determine the effect of the consumption of indigenous probiotic Lactobacillus plantarum Dad-13 powder in overweight adults in Yogyakarta(Indonesia).METHODS Sixty overweight volunteers with a body mass index(BMI)equal to or greater than 25 consume indigenous probiotic powder L.plantarum Dad-13(2×109 CFU/gram/sachet)for 90 d.The study was a randomized,double-blind,placebocontrolled study.The volunteers filled in a diary on a daily basis,which consisted of questions on study product intake(only during ingestion period),other food intake,number of bowel movements,fecal quality(consistency and color),any medications received,and any symptom of discomfort,such as diarrhea,constipation,vomiting,gassing,sensation of illness,etc.Fecal samples and the subjects’diaries were collected on the morning of day 10+1,which was marked as the end of the baseline period and the start of the ingestion period.During the ingestion period(from day 11 to day 101),several parameters to measure and analyze the results included body weight and height(once a month),the lipid profile,GM analysis using MiSeq,short-chain fatty acid(SCFA)analysis using gas chromatography,and the measurement of fecal pH using a pH meter.RESULTS The consumption of indigenous probiotic powder L.plantarum Dad-13 caused the average body weight and BMI of the probiotic group to decrease from 84.54±17.64 kg to 83.14±14.71 kg and 33.10±6.15 kg/m2 to 32.57±5.01 kg/m2,respectively.No significant reduction of body weight and BMI in the placebo group was observed.An analysis of the microbiota showed that the number of Bacteroidetes,specifically Prevotella,increased significantly,while that of Firmicutes significantly decreased.No significant change in lipid profile in both groups was found.Also,no significant change in SCFAs(e.g.,butyrate,propionate,acetic acid)and pH level was found after the consumption of the probiotic.CONCLUSION No significant differences in pH before and after ingestion were observed in both the probiotic and placebo groups as well as in the lipid profile of both cholesterol and triglyceride,high-density lipoprotein(HDL),low-density lipoprotein(LDL),and the LDL/HDL ratio.In addition,no significant changes in the concentration of SCFAs(e.g.,acetic acid,propionate,and butyrate)were found after consumption.Interestingly,a significant decrease in body weight and BMI(P<0.05)was determined in the treatment group.An analysis of GM shows that L.plantarum Dad-13 caused the Firmicutes population to decrease and the Bacteroidetes population(especially Prevotella)to increase.展开更多
Compound-specific stable isotope analysis of individual amino acids(CSIA-AA)has been widely used in ecological and biogeochemical studies.It has been proven to be powerful in tracing the diet sources and trophic inter...Compound-specific stable isotope analysis of individual amino acids(CSIA-AA)has been widely used in ecological and biogeochemical studies.It has been proven to be powerful in tracing the diet sources and trophic interactions.However,assessing the N sources of mesopelagic fishes has been inconclusive because the mesopelagic fishes’unique domain(water depth ranged from 0 to 1000 m)and unresolved nitrogen isotopes of various forms.This study proposes a new method for coupling instruments(ion chromatography and PreconIRMS)and chemical method of oxidation-reduction of amino acids,and also combinedδ15N of AAs withδ13C of fatty acids(FAs)to analyze the trophic interactions of mesopelagic fishes in the South China Sea(SCS).AAs were isolated by ion chromatography with high peak resolution and collected by an automated fraction collector.The chemical method then converted the AAs into N2 O with a robust oxidation yields and suitable molar ratio of NH2 OH to.Finally,theδ15N of AAs at 20 nmol were measured with a reasonable precision(<0.6‰).With this method,this study report the first batch high precisionδ15N of AAs andδ13C of FAs of mesopelagic fishes collected from SCS.Diaphus luetkeni,Chauliodus minimus and Bathygadus antrodes showed similarδ13C values of 20:4 n-6(~-28‰),while Argyropelecus affinis and Stomias had similar values(~-32‰).These results reflect that mesopelagic fishes had complex diet sources.An increase of 4‰inδ15N of glutamic acid(Glu)was found between piscivorous and planktivorous fishes,which might suggest a trophic discrimination factor of mesopelagic fishes in the SCS.This study usedδ13C of 20:4 n-6 to reveal the diet sources of mesopelagic fishes andδ15N of Glu to clarify trophic level between piscivorous and planktivorous fishes.Thus,this combinative method could therefore ultimately be applied in a variety of deep-sea ecosystem.展开更多
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
Auxin plays a critical role in lateral root(LR)formation.The signaling module composed of auxin-response factors(ARFs)and lateral organ boundaries domain transcription factors mediates auxin signaling to control almos...Auxin plays a critical role in lateral root(LR)formation.The signaling module composed of auxin-response factors(ARFs)and lateral organ boundaries domain transcription factors mediates auxin signaling to control almost every stage of LR development.Here,we show that auxin-induced degradation of the APETALA2/Ethylene Responsive Factor(AP2/ERF)transcription factor ERF13,dependent on MITOGENACTIVATED PROTEIN KINASE MPK14-mediated phosphorylation,plays an essential role in LR development.Overexpression of ERF13 results in restricted passage of the LR primordia through the endodermal layer,greatly reducing LR emergence,whereas the erf13 mutants showed an increase in emerged LR.ERF13 inhibits the expression of 3-ketoacyl-CoA synthase16(KCS16),which encodes a fatty acid elongase involved in very-long-chain fatty acid(VLCFA)biosynthesis.Overexpression of KCS16 or exogenous VLCFA treatment rescues the LR emergence defects in ERF13 overexpression lines,indicating a role downstream of the auxin-MPK14-ERF13 signaling module.Collectively,our study uncovers a novel molecular mechanism by which MPK14-mediated auxin signaling modulates LR development via ERF13-regulated VLCFA biosynthesis.展开更多
Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it techn...Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method.Levels of acyl-carnitines,which function to convey fatty acyls into mitochondria matrix forβ-oxidation,indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs.Herein,we report a robust,integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines.Using this method,we monitored changes in intermediary lipid profiles across Drosophila development under control(ND)and high-fat diet(HFD).We observed specific accumulations of medium-chain(C8-C12)and long-chain(≥C16)acyl-carnitines distinct to L3 larval and pupal stages,respectively.These observations suggested development-specific,chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development,which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra-and intra-mitochondrial acyl-CoA pools.We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs(accumulated as C12:0-carnitines in L3 stage)over C16:0-CoAs.Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs(C16-C18),leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6 A activity.HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa,thereby adversely affecting overall development.Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems.展开更多
Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibito...Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.展开更多
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.
文摘The 13C-labeled fatty acids octanoic-1-13C acid and palmitic-1-13C acid were synthetically prepared from Ba 13CO3. The yield of the former was more than 90% and that of the latter was above 85%. MS, IR, 1H-NMR and 13NMR were performed to analyze the structures of the two 13C-fatty acids, compared with their unlabeled fatty acids.
基金National Natural Science Foundation of China(82070398,81922008)Key Basic Research Projects of Basic Strengthening Plan(2022-JCJQ-ZD-095-00)Top Young Talents Special Support Program in Shaanxi Province(2020).
文摘Background Diabetic cardiomyopathy (DCM) causes the myocardium to rely on fatty acid β-oxidation for energy. The accumulation of intracellular lipids and fatty acids in the myocardium usually results in lipotoxicity, which impairs myocardial function. Adipsin may play an important protective role in the pathogenesis of DCM. The aim of this study is to investigate the regulatory effect of Adipsin on DCM lipotoxicity and its molecular mechanism.MethodsA high-fat diet (HFD)-induced type 2 diabetes mellitus model was constructed in mice with adipose tissue-specific overexpression of Adipsin (Adipsin-Tg). Liquid chromatography-tandem mass spectrometry (LC–MS/MS), glutathione-S-transferase (GST) pull-down technique, Co-immunoprecipitation (Co-IP) and immunofluorescence colocalization analyses were used to investigate the molecules which can directly interact with Adipsin. The immunocolloidal gold method was also used to detect the interaction between Adipsin and its downstream modulator.ResultsThe expression of Adipsin was significantly downregulated in the HFD-induced DCM model (P < 0.05). Adipose tissue-specific overexpression of Adipsin significantly improved cardiac function and alleviated cardiac remodeling in DCM (P < 0.05). Adipsin overexpression also alleviated mitochondrial oxidative phosphorylation function in diabetic stress (P < 0.05). LC–MS/MS analysis, GST pull-down technique and Co-IP studies revealed that interleukin-1 receptor-associated kinase-like 2 (Irak2) was a downstream regulator of Adipsin. Immunofluorescence analysis also revealed that Adipsin was co-localized with Irak2 in cardiomyocytes. Immunocolloidal gold electron microscopy and Western blotting analysis indicated that Adipsin inhibited the mitochondrial translocation of Irak2 in DCM, thus dampening the interaction between Irak2 and prohibitin (Phb)-optic atrophy protein 1 (Opa1) on mitochondria and improving the structural integrity and function of mitochondria (P < 0.05). Interestingly, in the presence of Irak2 knockdown, Adipsin overexpression did not further alleviate myocardial mitochondrial destruction and cardiac dysfunction, suggesting a downstream role of Irak2 in Adipsin-induced responses (P < 0.05). Consistent with these findings, overexpression of Adipsin after Irak2 knockdown did not further reduce the accumulation of lipids and their metabolites in the cardiac myocardium, nor did it enhance the oxidation capacity of cardiomyocytes expose to palmitate (PA) (P < 0.05). These results indicated that Irak2 may be a downstream regulator of Adipsin.ConclusionsAdipsin improves fatty acid β-oxidation and alleviates mitochondrial injury in DCM. The mechanism is related to Irak2 interaction and inhibition of Irak2 mitochondrial translocation.
基金This study is funded by the special funds from the National Key Basic Research Program of China under contract Nos 2006CB400601 and 2004CB720505the National Natural Science Foundation of China under contract Nos 90211009,40476037 and 40476036+2 种基金Shanghai Rising-star Project in China under contract No.04QMX1420the Program for New Century Excellent Talents in University of China under contract No.NCET-04-0424the Ministry of Education of China under contract No.PCSIRT0427.
文摘Particulate samples were collected from the Changjiang river system during a flood period, in May 1997, and POC, stable isotope and lipids associated with particles were examined. Results showed the decrease （0.84% ～ 1.88%） of organic carbon content from the upper reaches to the estuary.δ^13 values of particulate organic carbon was in the range of -24.9×10^-3 to -26.6×10^-3, which were close to the isotopic signature of continental C3 vegetation. Total particulate n-alkanes concentrations varied from 1.4 to 10.1μg/dm^3,or from 23.7 to 107μg/g of total suspended matter. Fatty acids were present in all the samples, from 1.4 to 5.4μg/dm^3, with saturated and unsaturated straight-chain and branched compounds in the carbon number range from C12 to C30. Both δ^13 and the ratio of carbon content to nitrogen content indicate the predominance of terrestrial inputs （soil organic matter） among the particles. The biomarker approach has been used to identify the relative portion of terrigenous and autochthonous fraction in the particulate samples. The distribution of fatty acids suggests a striking phytoplanktonic and microbial signal in most particle samples. The terrestrial alkanes are used to estimate the contribution of terrestrial inputs along the mainstream.
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.
基金Supported by Ristekdikti Kalbe-Science Awards,No.048/KFLegal/RKSA/I/2019.
文摘BACKGROUND Shifting on lifestyle,diet,and physical activity contributed on increasing number of obese people around the world.Multiple factors influence the development of obesity.Some research suggested that gut microbiota(GM)plays an important role in nutrient absorption and energy regulation of individuals,thus affecting their nutritional status.Report of Indonesia Basic Health Research showed that the prevalence of obesity in every province tended to increase.Although the root cause of obesity is excessive calorie intake compared with expenditure,the differences in gut microbial ecology between healthy and obese humans may affect energy homeostasis.GM affect body weight,especially obesity.Probiotics that are consumed while alive and able to colonize in the intestine are expected to increase the population of good bacteria,especially Bifidobacteria and Lactobacilli,and suppress pathogens such as Enterobacteriaceae and Staphylococcus.The strain of L.plantarum Dad-13 has been demonstrated to survive and colonize in the gastrointestinal tract of healthy Indonesian adults who consume fermented milk containing L.plantarum Dad-13.The consumption of probiotic L.plantarum Dad-13 powder decreased E.coli and non-E.coli coliform bacteria in school-aged children in Indonesia.L.plantarum is a dominant bacterium in the average Indonesian’s GM.For this reason,this bacterium is probably a more suitable probiotic for Indonesians.AIM To determine the effect of the consumption of indigenous probiotic Lactobacillus plantarum Dad-13 powder in overweight adults in Yogyakarta(Indonesia).METHODS Sixty overweight volunteers with a body mass index(BMI)equal to or greater than 25 consume indigenous probiotic powder L.plantarum Dad-13(2×109 CFU/gram/sachet)for 90 d.The study was a randomized,double-blind,placebocontrolled study.The volunteers filled in a diary on a daily basis,which consisted of questions on study product intake(only during ingestion period),other food intake,number of bowel movements,fecal quality(consistency and color),any medications received,and any symptom of discomfort,such as diarrhea,constipation,vomiting,gassing,sensation of illness,etc.Fecal samples and the subjects’diaries were collected on the morning of day 10+1,which was marked as the end of the baseline period and the start of the ingestion period.During the ingestion period(from day 11 to day 101),several parameters to measure and analyze the results included body weight and height(once a month),the lipid profile,GM analysis using MiSeq,short-chain fatty acid(SCFA)analysis using gas chromatography,and the measurement of fecal pH using a pH meter.RESULTS The consumption of indigenous probiotic powder L.plantarum Dad-13 caused the average body weight and BMI of the probiotic group to decrease from 84.54±17.64 kg to 83.14±14.71 kg and 33.10±6.15 kg/m2 to 32.57±5.01 kg/m2,respectively.No significant reduction of body weight and BMI in the placebo group was observed.An analysis of the microbiota showed that the number of Bacteroidetes,specifically Prevotella,increased significantly,while that of Firmicutes significantly decreased.No significant change in lipid profile in both groups was found.Also,no significant change in SCFAs(e.g.,butyrate,propionate,acetic acid)and pH level was found after the consumption of the probiotic.CONCLUSION No significant differences in pH before and after ingestion were observed in both the probiotic and placebo groups as well as in the lipid profile of both cholesterol and triglyceride,high-density lipoprotein(HDL),low-density lipoprotein(LDL),and the LDL/HDL ratio.In addition,no significant changes in the concentration of SCFAs(e.g.,acetic acid,propionate,and butyrate)were found after consumption.Interestingly,a significant decrease in body weight and BMI(P<0.05)was determined in the treatment group.An analysis of GM shows that L.plantarum Dad-13 caused the Firmicutes population to decrease and the Bacteroidetes population(especially Prevotella)to increase.
基金The National Basic Research Program(973 Program)of China under contract No.2014CB441502the National Natural Science Foundation of China under contract No.41876074the Cross-research Center Project by QNLM under contract No.JCZX202007。
文摘Compound-specific stable isotope analysis of individual amino acids(CSIA-AA)has been widely used in ecological and biogeochemical studies.It has been proven to be powerful in tracing the diet sources and trophic interactions.However,assessing the N sources of mesopelagic fishes has been inconclusive because the mesopelagic fishes’unique domain(water depth ranged from 0 to 1000 m)and unresolved nitrogen isotopes of various forms.This study proposes a new method for coupling instruments(ion chromatography and PreconIRMS)and chemical method of oxidation-reduction of amino acids,and also combinedδ15N of AAs withδ13C of fatty acids(FAs)to analyze the trophic interactions of mesopelagic fishes in the South China Sea(SCS).AAs were isolated by ion chromatography with high peak resolution and collected by an automated fraction collector.The chemical method then converted the AAs into N2 O with a robust oxidation yields and suitable molar ratio of NH2 OH to.Finally,theδ15N of AAs at 20 nmol were measured with a reasonable precision(<0.6‰).With this method,this study report the first batch high precisionδ15N of AAs andδ13C of FAs of mesopelagic fishes collected from SCS.Diaphus luetkeni,Chauliodus minimus and Bathygadus antrodes showed similarδ13C values of 20:4 n-6(~-28‰),while Argyropelecus affinis and Stomias had similar values(~-32‰).These results reflect that mesopelagic fishes had complex diet sources.An increase of 4‰inδ15N of glutamic acid(Glu)was found between piscivorous and planktivorous fishes,which might suggest a trophic discrimination factor of mesopelagic fishes in the SCS.This study usedδ13C of 20:4 n-6 to reveal the diet sources of mesopelagic fishes andδ15N of Glu to clarify trophic level between piscivorous and planktivorous fishes.Thus,this combinative method could therefore ultimately be applied in a variety of deep-sea ecosystem.
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This research was supported by the National Natural Science Foundation of China(Projects 31670275,31470371,31500227,and 31900246)the Shandong Province Natural Science Foundation Major Basic Research Program(2017C03)+1 种基金the China Postdoctoral Science Foundation(2019M662332,2019T120582)the Special Support for Post-doc Creative Funding in Shandong(201901010).
文摘Auxin plays a critical role in lateral root(LR)formation.The signaling module composed of auxin-response factors(ARFs)and lateral organ boundaries domain transcription factors mediates auxin signaling to control almost every stage of LR development.Here,we show that auxin-induced degradation of the APETALA2/Ethylene Responsive Factor(AP2/ERF)transcription factor ERF13,dependent on MITOGENACTIVATED PROTEIN KINASE MPK14-mediated phosphorylation,plays an essential role in LR development.Overexpression of ERF13 results in restricted passage of the LR primordia through the endodermal layer,greatly reducing LR emergence,whereas the erf13 mutants showed an increase in emerged LR.ERF13 inhibits the expression of 3-ketoacyl-CoA synthase16(KCS16),which encodes a fatty acid elongase involved in very-long-chain fatty acid(VLCFA)biosynthesis.Overexpression of KCS16 or exogenous VLCFA treatment rescues the LR emergence defects in ERF13 overexpression lines,indicating a role downstream of the auxin-MPK14-ERF13 signaling module.Collectively,our study uncovers a novel molecular mechanism by which MPK14-mediated auxin signaling modulates LR development via ERF13-regulated VLCFA biosynthesis.
基金supported by the National Key R&D Program of China(2018YFA0506900,2018YFA0800901)the Strategic Priority Research Program of the Chinese Academy of Sciences(XDA12030211)the National Natural Science Foundation of China(31671226,31871194)。
文摘Acyl-coenzyme A thioesters(acyl-CoAs)denote a key class of intermediary metabolites that lies at the hub of major metabolic pathways.The great diversity in polarity between short-and long-chain acylCoAs makes it technically challenging to cover an inclusive range of acyl-CoAs within a single method.Levels of acyl-carnitines,which function to convey fatty acyls into mitochondria matrix forβ-oxidation,indicate the efficiency of mitochondrial import and utilization of corresponding acyl-CoAs.Herein,we report a robust,integrated platform to allow simultaneous quantitation of endogenous acyl-CoAs and acyl-carnitines.Using this method,we monitored changes in intermediary lipid profiles across Drosophila development under control(ND)and high-fat diet(HFD).We observed specific accumulations of medium-chain(C8-C12)and long-chain(≥C16)acyl-carnitines distinct to L3 larval and pupal stages,respectively.These observations suggested development-specific,chain length-dependent disparity in metabolic fates of acyl-CoAs across Drosophila development,which was validated by deploying the same platform to monitor isotope incorporation introduced from labelled 12:0 and 16:0 fatty acids into extra-and intra-mitochondrial acyl-CoA pools.We found that pupal mitochondria preferentially import and oxidise C12:0-CoAs(accumulated as C12:0-carnitines in L3 stage)over C16:0-CoAs.Preferential oxidation of medium-chain acyl-CoAs limits mitochondrial utilization of long-chain acyl-CoAs(C16-C18),leading to pupal-specific accumulation of long-chain acyl-carnitines mediated by enhanced CPT1-6 A activity.HFD skewed C16:0-CoAs towards catabolism over anabolism in pupa,thereby adversely affecting overall development.Our developed platform emphasizes the importance of integrating biological knowledge in the design of pathway-oriented platforms to derive maximal physiological insights from analysis of complex biological systems.
基金supported by the National Natural Science Foundation of China(No.82070883)Scientific Research Foundation for high-level faculty,China Pharmaceutical University(Nanjing,China)。
文摘Hepatocellular carcinoma(HCC)is an aggressive human cancer with increasing incidence worldwide.Multiple efforts have been made to explore pharmaceutical therapies to treat HCC,such as targeted tyrosine kinase inhibitors,immune based therapies and combination of chemotherapy.However,limitations exist in current strategies including chemoresistance for instance.Tumor initiation and progression is driven by reprogramming of metabolism,in particular during HCC development.Recently,metabolic associated fatty liver disease(MAFLD),a reappraisal of new nomenclature for nonalcoholic fatty liver disease(NAFLD),indicates growing appreciation of metabolism in the pathogenesis of liver disease,including HCC,thereby suggesting new strategies by targeting abnormal metabolism for HCC treatment.In this review,we introduce directions by highlighting the metabolic targets in glucose,fatty acid,amino acid and glutamine metabolism,which are suitable for HCC pharmaceutical intervention.We also summarize and discuss current pharmaceutical agents and studies targeting deregulated metabolism during HCC treatment.Furthermore,opportunities and challenges in the discovery and development of HCC therapy targeting metabolism are discussed.
