Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal g...Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal ganglia.The predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal degeneration.Among the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis pathway.Currently there is no effective treatment to prevent the inexorable course of these disorders.The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN.Recently,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative stress.In addition,PKAN fibroblasts showed a morphological senescence-like phenotype.Interestingly,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression.However,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein.The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts.Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations.Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment.The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate.The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available,and monitoring its effect on the pathophysiological changes,can help for a better therapeutic strategy.In addition,these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.展开更多
During T-cell-mediated inflammatory responses,T cells are activated upon recognizing specific antigens presented by antigenpresenting cells.This recognition initiates signaling through the TCR and CD28,leading to thei...During T-cell-mediated inflammatory responses,T cells are activated upon recognizing specific antigens presented by antigenpresenting cells.This recognition initiates signaling through the TCR and CD28,leading to their activation and subsequent clonal expansion.Within the signaling cascades triggered by TCR and CD28 engagement,the CD28-PI3K pathway serves as a central regulator of metabolic reprogramming in T cells,supporting the biosynthetic needs essential for their effective proliferation.In this study,we found that the regulation of PANK4 plays a role in TCR/CD28-mediated CD4^(+)T-cell proliferation by regulating de novo lipid synthesis.The CD28 signaling pathway negatively regulates PANK4 through direct binding with PDK1,thereby controlling de novo lipid synthesis for CD4^(+)T-cell proliferation.Interestingly,we found that Pank4-deficient CD4^(+)T cells enhance coenzyme A synthesis and glutaminolysis,whereby glutamine contributes carbon for fatty acid synthesis and provides nitrogen for coenzyme A biosynthesis.The regulatory role of PANK4 in CD4^(+)T-cell proliferation was confirmed in models of experimental colitis and influenza A virus infection,where Pank4-deficient CD4^(+)T cells exhibited greater expansion than their wild-type counterparts when co-transferred.Our findings suggest that PANK4 regulation of de novo lipid synthesis is crucial for TCR/CD28-induced CD4^(+)T-cell proliferation and represents a potential target for modulating general CD4^(+)T-cell responses.展开更多
Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated ＂acanthocytic＂ red blood cells. The clinical manifestation...Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated ＂acanthocytic＂ red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington＇s disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.展开更多
Results from 12 switchback field trials involving 1216 cows were combined to assess the effects of a protected B vitamin blend (BVB) upon milk yield (kg), fat percentage (%), protein %, fat yield (kg) and protein yiel...Results from 12 switchback field trials involving 1216 cows were combined to assess the effects of a protected B vitamin blend (BVB) upon milk yield (kg), fat percentage (%), protein %, fat yield (kg) and protein yield (kg) in primiparous and multiparous cows. Trials consisted of 3 test periods executed in the order control-test-control. No diet changes other than the inclusion of 3 grams/cow/ day of the BVB during the test period occurred. Means from the two control periods were compared to results obtained during the test period using a paired T test. Cows include in the analysis were between 45 and 300 days in milk (DIM) at the start of the experiment and were continuously available for all periods. The provision of the BVB resulted in increased (P < 0.05) milk, fat %, protein %, fat yield and protein yield. Regression models showed that the amount of milk produced had no effect upon the magnitude of the increase in milk components. The increase in milk was greatest in early lactation and declined with DIM. Protein and fat % increased with DIM in mature cows, but not in first lactation cows. Differences in fat yields between test and control feeding periods did not change with DIM, but the improvement in protein yield in mature cows declined with DIM. These results indicate that the BVB provided economically important advantages throughout lactation, but expected results would vary with cow age and stage of lactation.展开更多
Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for ...Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for every nutrient in actual dietary practice. Design: We evaluated (1) whether the DRIs for all nutrients can be fulfilled in a formula with energy and protein exceeding their DRIs, (2) whether the DRIs for all nutrients can be fulfilled in a formula prepared in accordance with Japanese government-recommended weaning guidelines, and (3) what kinds of formulas can be prepared if the DRIs for all nutrients are fulfilled without referring to the weaning guidelines. Setting: Simulation of diet menu on the basis of published data in our university and survey of diet menu in a university hospital attached to a national medical school. Subjects: The three types of formulas were planned for ten days. Results: It was impossible to simultaneously fulfil the DRIs for 6 - 8-month-old infants concerning pantothenic acid, vitamin D, and iron and those for 9 - 11-month-old infants concerning these nutrients plus protein. Conclusion: According to the DRIs-2010, the DRI for all nutrients could not be fulfilled in an ingestible formula.展开更多
Objective: It has been suggested that pantothenic acid may have antibacterial and skin softening activity. The aim of this study was to explore the feasibility, tolerability, safety and preliminary efficacy of oral ad...Objective: It has been suggested that pantothenic acid may have antibacterial and skin softening activity. The aim of this study was to explore the feasibility, tolerability, safety and preliminary efficacy of oral administration of a dietary supplement containing pantothenic acid in healthy human males and females with mild to moderate facial acne vulgaris. Methods: An open-label, single arm study of healthy adults who had been previously diagnosed with mild to moderate acne vulgaris was performed. Subjects were asked to take the study agent, a dietary supplement containing pantothenic acid, for eight weeks. The primary endpoint of the study was to assess the feasibility of oral administration of the study agent in subjects over an eight week period. Safety and tolerability were measured utilizing the assessment of adverse events by the National Cancer Institute’s Common Criteria for Adverse Event Reporting. Secondary endpoints measuring the efficacy of an oral panthothetic acid dietary supplement for the treatment of mild to moderate facial acne utilized changes in the extent of global facial skin blemishes, assessment of quality of life utilizing the Dermatology Life Quality Index (DLQI) and analysis of questions about the subject's beliefs and attitudes towards skin care and lifestyle. Results: Eleven subjects were enrolled and ten completed the study (90.9%). There were no reported adverse events. Of the 10 evaluable subjects, the average age (mean ± SD) was 31.8 ± 8. Analysis of the global number of skin blemishes demonstrated a significant mean reduction in lesion count following the use of the study agent at week 8 (endpoint) (11.18 ± 6.38, p = 0.02) compared to the average number of baseline blemishes (20.45 ± 10.44). DLQI scores were significantly lower at week 8 vs. baseline (p = 0.0194). Conclusions: The results from this study indicated that the administration of a pantothenic based dietary supplement in healthy human adults with mild to moderate acne vulgaris is feasible, safe and well tolerated. Secondary analysis shows that administration of the study agent significantly reduced global facial blemishes. Further randomized, placebo-controlled trials are warranted.展开更多
This experiment was conducted to study the effects of pantothenic acid on the growth performance,slaughter performance, lipid metabolism, and antioxidant function of one-to four-week-old Wulong geese and determine the...This experiment was conducted to study the effects of pantothenic acid on the growth performance,slaughter performance, lipid metabolism, and antioxidant function of one-to four-week-old Wulong geese and determine the appropriate supplemental level of pantothenic acid. A total of 360 one-day-old Wulong geese were randomly divided into 6 groups with 6 replicates per group and 10 geese(5 males and 5 females) per replicate. The geese in group Ⅰ(control group) were fed a basal diet, and the geese in groups Ⅱ to Ⅵ(experimental groups) were given the basal diet supplemented with 8, 15, 30, 60, and120 mg/kg pantothenic acid, respectively. The experiment lasted for 4 weeks. Based on the results of unrelated comparative analysis, the body weight was the highest when the dietary pantothenic acid level was 27.57 mg/kg. When the dietary pantothenic acid level was 26.17 mg/kg, the average daily gain peaked. When the dietary pantothenic acid level was 15.50 mg/kg, the feed:gain ratio was the lowest.The percentage of abdominal fat in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ(P < 0.05). The content of total cholesterol in serum in groups III to Ⅴ was significantly lower than that in group Ⅰ(P < 0.05). The triglyceride content in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ(P < 0.01). The high-density lipoprotein—cholesterol content in group Ⅳ was significantly higher than that in group Ⅰ(P < 0.05). The total antioxidant capacity of serum and liver in group Ⅳ was significantly higher than that in group Ⅰ(P < 0.05). The malondialdehyde content in the liver in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ(P < 0.05), Glutathione peroxidase activity in the serum in group Ⅳ was significantly higher than that in group Ⅰ(P < 0.05). Glutathione peroxidase activity in the liver in groups Ⅳ and Ⅴ was significantly higher than that in group Ⅰ(P < 0.01). The addition of pantothenic acid in the diet of one-to four-week-old Wulong geese significantly affected the growth performance,slaughter performance, lipid metabolism, and antioxidant function of the geese. In terms of economic benefits, the optimal supplemental level of pantothenic acid in one-to four-week-old geese was15.50 mg/kg.展开更多
Pantothenic acid deficiency(PAD)in animals causes growth depression,fasting hypoglycemia and impaired lipid and glucose metabolism.However,a systematic multi-omics analysis of effects of PAD on hepatic function has ap...Pantothenic acid deficiency(PAD)in animals causes growth depression,fasting hypoglycemia and impaired lipid and glucose metabolism.However,a systematic multi-omics analysis of effects of PAD on hepatic function has apparently not been reported.We investigated liver proteome and metabolome changes induced by PAD to explain its effects on growth and liver metabolic disorders.Pekin ducks(1-dold,n=128)were allocated into 2 groups,with 8 replicates and 8 birds per replicate.For 16 d,all ducks had ad libitum access to either a PAD or a pantothenic acid adequate(control,CON)diet,formulated by supplementing a basal diet with 0 or 8 mg pantothenic acid/kg of diet,respectively.Liver enlargement,elevated liver glycogen concentrations and decreased liver concentrations of triglyceride and unsaturated fatty acids were present in the PAD group compared to the CON group.Based on integrated liver proteomics and metabolomics,PAD mainly affected glycogen synthesis and degradation,glycolysis and gluconeogenesis,tricarboxylic acid(TCA)cycle,peroxisome proliferator-activated receptor(PPAR)signaling pathway,fatty acid beta oxidation,and oxidative phosphorylation.Selected proteins were confirmed by Western blotting.Downregulation of proteins and metabolites involved in glycogen synthesis and degradation,glycolysis and gluconeogenesis implied that these processes were impaired in PAD ducks,which could have contributed to fasting hypoglycemia,liver glycogen storage,insufficient ATP production,and growth retardation.In contrast,PAD also upregulated proteins and metabolites involved in fatty acid beta oxidation,the TCA cycle,and oxidative phosphorylation processes in the liver;presumably compensatory responses to produce ATP.We inferred that PAD decreased liver triglyceride and unsaturated fatty acids by activating fatty acid beta oxidation and impairing unsaturated fatty acid synthesis.These findings contributed to our understanding of the mechanisms of PAD-induced changes in hepatic metabolism.展开更多
基金supported by FIS PI16/00786 grant,Instituto de Salud Carlos Ⅲ,Spain and Fondo Europeo de Desarrollo Regional(FEDER-Unión Europea),Proyectos de Investigación de Excelencia de la Junta de Andalucía CTS-5725AEPMI(Asociación de Enfermos de Patología Mitocondrial) and ENACH(Asociación de Enfermos de Neurodegeneración con Acumulación Cerebral de Hierro)(to JASA)
文摘Neurodegeneration with brain iron accumulation is a broad term that describes a heterogeneous group of progressive and invalidating neurologic disorders in which iron deposits in certain brain areas,mainly the basal ganglia.The predominant clinical symptoms include spasticity,progressive dystonia,Parkinson's disease-like symptoms,neuropsychiatric alterations,and retinal degeneration.Among the neurodegeneration with brain iron accumulation disorders,the most frequent subtype is pantothenate kinase-associated neurodegeneration(PKAN) caused by defects in the gene encoding the enzyme pantothenate kinase 2(PANK2)which catalyzed the first reaction of the coenzyme A biosynthesis pathway.Currently there is no effective treatment to prevent the inexorable course of these disorders.The aim of this review is to open up a discussion on the utility of using cellular models derived from patients as a valuable tool for the development of precision medicine in PKAN.Recently,we have described that dermal fibroblasts obtained from PKAN patients can manifest the main pathological changes of the disease such as intracellular iron accumulation accompanied by large amounts of lipofuscin granules,mitochondrial dysfunction and a pronounced increase of markers of oxidative stress.In addition,PKAN fibroblasts showed a morphological senescence-like phenotype.Interestingly,pantothenate supplementation,the substrate of the PANK2 enzyme,corrected all pathophysiological alterations in responder PKAN fibroblasts with low/residual PANK2 enzyme expression.However,pantothenate treatment had no favourable effect on PKAN fibroblasts harbouring mutations associated with the expression of a truncated/incomplete protein.The correction of pathological alterations by pantothenate in individual mutations was also verified in induced neurons obtained by direct reprograming of PKAN fibroblasts.Our observations indicate that pantothenate supplementation can increase/stabilize the expression levels of PANK2 in specific mutations.Fibroblasts and induced neurons derived from patients can provide a useful tool for recognizing PKAN patients who can respond to pantothenate treatment.The presence of low but significant PANK2 expression which can be increased in particular mutations gives valuable information which can support the treatment with high dose of pantothenate.The evaluation of personalized treatments in vitro of fibroblasts and neuronal cells derived from PKAN patients with a wide range of pharmacological options currently available,and monitoring its effect on the pathophysiological changes,can help for a better therapeutic strategy.In addition,these cell models will be also useful for testing the efficacy of new therapeutic options developed in the future.
基金supported by grants from the National Research Foundation of Korea(grant numbers:NRF-2021R1A2C3011211,NRF-2022M3A9I2017587,and NRF-2022R1C1C1003619)Creative-Pioneering Researchers Program(grant number:370-2024114)from Seoul National University,the Ministry of Food and Drug Safety in Korea(grant number:RS-2024-00331849)Ascending SNU Future Leader Fellowship through Seoul National University.
文摘During T-cell-mediated inflammatory responses,T cells are activated upon recognizing specific antigens presented by antigenpresenting cells.This recognition initiates signaling through the TCR and CD28,leading to their activation and subsequent clonal expansion.Within the signaling cascades triggered by TCR and CD28 engagement,the CD28-PI3K pathway serves as a central regulator of metabolic reprogramming in T cells,supporting the biosynthetic needs essential for their effective proliferation.In this study,we found that the regulation of PANK4 plays a role in TCR/CD28-mediated CD4^(+)T-cell proliferation by regulating de novo lipid synthesis.The CD28 signaling pathway negatively regulates PANK4 through direct binding with PDK1,thereby controlling de novo lipid synthesis for CD4^(+)T-cell proliferation.Interestingly,we found that Pank4-deficient CD4^(+)T cells enhance coenzyme A synthesis and glutaminolysis,whereby glutamine contributes carbon for fatty acid synthesis and provides nitrogen for coenzyme A biosynthesis.The regulatory role of PANK4 in CD4^(+)T-cell proliferation was confirmed in models of experimental colitis and influenza A virus infection,where Pank4-deficient CD4^(+)T cells exhibited greater expansion than their wild-type counterparts when co-transferred.Our findings suggest that PANK4 regulation of de novo lipid synthesis is crucial for TCR/CD28-induced CD4^(+)T-cell proliferation and represents a potential target for modulating general CD4^(+)T-cell responses.
文摘Neuroacanthocytosis is an autosomal recessive or dominant inherited disease characterized by widespread, non-specific nervous system symptoms, or spiculated ＂acanthocytic＂ red blood cells. The clinical manifestations typically involve chorea and dystonia, or a range of other movement disorders. Psychiatric and cognitive symptoms may also be present. The two core neuroacanthocytosis syndromes, in which acanthocytosis is atypical, are autosomal recessive chorea-acanthocytosis and X-linked McLeod syndrome. Acanthocytes are found in a smaller proportion of patients with Huntington＇s disease-like 2 and pantothenate kinase-associated neurodegeneration. Because the clinical manifestations are diverse and complicated, in this review we present features of inheritance, age of onset, neuroimaging and laboratory findings, as well as the spectrum of central and peripheral neurological abnormalities and extraneuronal involvement to help distinguish the four specific syndromes.
文摘Results from 12 switchback field trials involving 1216 cows were combined to assess the effects of a protected B vitamin blend (BVB) upon milk yield (kg), fat percentage (%), protein %, fat yield (kg) and protein yield (kg) in primiparous and multiparous cows. Trials consisted of 3 test periods executed in the order control-test-control. No diet changes other than the inclusion of 3 grams/cow/ day of the BVB during the test period occurred. Means from the two control periods were compared to results obtained during the test period using a paired T test. Cows include in the analysis were between 45 and 300 days in milk (DIM) at the start of the experiment and were continuously available for all periods. The provision of the BVB resulted in increased (P < 0.05) milk, fat %, protein %, fat yield and protein yield. Regression models showed that the amount of milk produced had no effect upon the magnitude of the increase in milk components. The increase in milk was greatest in early lactation and declined with DIM. Protein and fat % increased with DIM in mature cows, but not in first lactation cows. Differences in fat yields between test and control feeding periods did not change with DIM, but the improvement in protein yield in mature cows declined with DIM. These results indicate that the BVB provided economically important advantages throughout lactation, but expected results would vary with cow age and stage of lactation.
文摘Objective: With regard to the 2010 edition of Dietary Reference Intakes for Japanese (DRIs-2010), we investigated whether the DRIs for two age groups, breast-fed infants aged 6-8 and 9-11 months, can be fulfilled for every nutrient in actual dietary practice. Design: We evaluated (1) whether the DRIs for all nutrients can be fulfilled in a formula with energy and protein exceeding their DRIs, (2) whether the DRIs for all nutrients can be fulfilled in a formula prepared in accordance with Japanese government-recommended weaning guidelines, and (3) what kinds of formulas can be prepared if the DRIs for all nutrients are fulfilled without referring to the weaning guidelines. Setting: Simulation of diet menu on the basis of published data in our university and survey of diet menu in a university hospital attached to a national medical school. Subjects: The three types of formulas were planned for ten days. Results: It was impossible to simultaneously fulfil the DRIs for 6 - 8-month-old infants concerning pantothenic acid, vitamin D, and iron and those for 9 - 11-month-old infants concerning these nutrients plus protein. Conclusion: According to the DRIs-2010, the DRI for all nutrients could not be fulfilled in an ingestible formula.
文摘Objective: It has been suggested that pantothenic acid may have antibacterial and skin softening activity. The aim of this study was to explore the feasibility, tolerability, safety and preliminary efficacy of oral administration of a dietary supplement containing pantothenic acid in healthy human males and females with mild to moderate facial acne vulgaris. Methods: An open-label, single arm study of healthy adults who had been previously diagnosed with mild to moderate acne vulgaris was performed. Subjects were asked to take the study agent, a dietary supplement containing pantothenic acid, for eight weeks. The primary endpoint of the study was to assess the feasibility of oral administration of the study agent in subjects over an eight week period. Safety and tolerability were measured utilizing the assessment of adverse events by the National Cancer Institute’s Common Criteria for Adverse Event Reporting. Secondary endpoints measuring the efficacy of an oral panthothetic acid dietary supplement for the treatment of mild to moderate facial acne utilized changes in the extent of global facial skin blemishes, assessment of quality of life utilizing the Dermatology Life Quality Index (DLQI) and analysis of questions about the subject's beliefs and attitudes towards skin care and lifestyle. Results: Eleven subjects were enrolled and ten completed the study (90.9%). There were no reported adverse events. Of the 10 evaluable subjects, the average age (mean ± SD) was 31.8 ± 8. Analysis of the global number of skin blemishes demonstrated a significant mean reduction in lesion count following the use of the study agent at week 8 (endpoint) (11.18 ± 6.38, p = 0.02) compared to the average number of baseline blemishes (20.45 ± 10.44). DLQI scores were significantly lower at week 8 vs. baseline (p = 0.0194). Conclusions: The results from this study indicated that the administration of a pantothenic based dietary supplement in healthy human adults with mild to moderate acne vulgaris is feasible, safe and well tolerated. Secondary analysis shows that administration of the study agent significantly reduced global facial blemishes. Further randomized, placebo-controlled trials are warranted.
文摘This experiment was conducted to study the effects of pantothenic acid on the growth performance,slaughter performance, lipid metabolism, and antioxidant function of one-to four-week-old Wulong geese and determine the appropriate supplemental level of pantothenic acid. A total of 360 one-day-old Wulong geese were randomly divided into 6 groups with 6 replicates per group and 10 geese(5 males and 5 females) per replicate. The geese in group Ⅰ(control group) were fed a basal diet, and the geese in groups Ⅱ to Ⅵ(experimental groups) were given the basal diet supplemented with 8, 15, 30, 60, and120 mg/kg pantothenic acid, respectively. The experiment lasted for 4 weeks. Based on the results of unrelated comparative analysis, the body weight was the highest when the dietary pantothenic acid level was 27.57 mg/kg. When the dietary pantothenic acid level was 26.17 mg/kg, the average daily gain peaked. When the dietary pantothenic acid level was 15.50 mg/kg, the feed:gain ratio was the lowest.The percentage of abdominal fat in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ(P < 0.05). The content of total cholesterol in serum in groups III to Ⅴ was significantly lower than that in group Ⅰ(P < 0.05). The triglyceride content in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ(P < 0.01). The high-density lipoprotein—cholesterol content in group Ⅳ was significantly higher than that in group Ⅰ(P < 0.05). The total antioxidant capacity of serum and liver in group Ⅳ was significantly higher than that in group Ⅰ(P < 0.05). The malondialdehyde content in the liver in groups Ⅲ and Ⅳ was significantly lower than that in group Ⅰ(P < 0.05), Glutathione peroxidase activity in the serum in group Ⅳ was significantly higher than that in group Ⅰ(P < 0.05). Glutathione peroxidase activity in the liver in groups Ⅳ and Ⅴ was significantly higher than that in group Ⅰ(P < 0.01). The addition of pantothenic acid in the diet of one-to four-week-old Wulong geese significantly affected the growth performance,slaughter performance, lipid metabolism, and antioxidant function of the geese. In terms of economic benefits, the optimal supplemental level of pantothenic acid in one-to four-week-old geese was15.50 mg/kg.
基金supported by the earmarked fund for China Agricultural Research System(CARS-42)the science and technology innovation project of Chinese Academy of Agricultural Sciences(CXGC-IAS-09)Taishan Industry Leadership Talent Project of Shandong province in China(TSCY20190108)。
文摘Pantothenic acid deficiency(PAD)in animals causes growth depression,fasting hypoglycemia and impaired lipid and glucose metabolism.However,a systematic multi-omics analysis of effects of PAD on hepatic function has apparently not been reported.We investigated liver proteome and metabolome changes induced by PAD to explain its effects on growth and liver metabolic disorders.Pekin ducks(1-dold,n=128)were allocated into 2 groups,with 8 replicates and 8 birds per replicate.For 16 d,all ducks had ad libitum access to either a PAD or a pantothenic acid adequate(control,CON)diet,formulated by supplementing a basal diet with 0 or 8 mg pantothenic acid/kg of diet,respectively.Liver enlargement,elevated liver glycogen concentrations and decreased liver concentrations of triglyceride and unsaturated fatty acids were present in the PAD group compared to the CON group.Based on integrated liver proteomics and metabolomics,PAD mainly affected glycogen synthesis and degradation,glycolysis and gluconeogenesis,tricarboxylic acid(TCA)cycle,peroxisome proliferator-activated receptor(PPAR)signaling pathway,fatty acid beta oxidation,and oxidative phosphorylation.Selected proteins were confirmed by Western blotting.Downregulation of proteins and metabolites involved in glycogen synthesis and degradation,glycolysis and gluconeogenesis implied that these processes were impaired in PAD ducks,which could have contributed to fasting hypoglycemia,liver glycogen storage,insufficient ATP production,and growth retardation.In contrast,PAD also upregulated proteins and metabolites involved in fatty acid beta oxidation,the TCA cycle,and oxidative phosphorylation processes in the liver;presumably compensatory responses to produce ATP.We inferred that PAD decreased liver triglyceride and unsaturated fatty acids by activating fatty acid beta oxidation and impairing unsaturated fatty acid synthesis.These findings contributed to our understanding of the mechanisms of PAD-induced changes in hepatic metabolism.
