Hepatic gluconeogenesis is a critical process that generates glucose from non-carbohydrate precursors during fasting to support vital organs like the brain and red blood cells. Postprandially, this process is rapidly ...Hepatic gluconeogenesis is a critical process that generates glucose from non-carbohydrate precursors during fasting to support vital organs like the brain and red blood cells. Postprandially, this process is rapidly suppressed to allow for glucose storage as glycogen and lipids in the liver. Failure to suppress gluconeogenesis after meals leads to elevated postprandial glucose levels, a key feature of type 2 diabetes. This dynamic switch is regulated by insulin and glucagon, but insulin resistance impairs this regulation. In this study, we identified a novel mechanism involving postprandial circulating hyaluronan(HA) and lysosomal hyaluronidase-1(HYAL1) that suppresses hepatic gluconeogenesis by rewiring hepatic metabolism and mitochondrial function. Hyal1 knockout(Hyal1 KO) mice exhibited increased gluconeogenesis, while liver-specific Hyal1 overexpression(Liv-Hyal1) mice showed reduced gluconeogenic activity. Transcriptomic analysis revealed minimal changes in liver gene expression due to Hyal1 deletion, but metabolomic profiling demonstrated that Hyal1 overexpression mitigated high-fat diet(HFD)-induced elevations in gluconeogenic pathway metabolites. Mechanistically, HYAL1-mediated HA digestion activates a feedback loop in HA synthesis, repartitioning the cellular uridine diphospho-N-acetyl-D-glucosamine(UDP-Glc NAc) pool. This reduces O-linked N-acetylglucosamine modification(O-Glc NAcylation) of mitochondrial ATP synthase subunits, decreasing ATP production and suppressing gluconeogenesis. Importantly, this pathway remains intact in the livers of HFD-fed, insulin-resistant mice. In summary, our findings reveal a new postprandial mechanism for regulating hepatic gluconeogenesis, highlighting the potential of enhancing postprandial HA levels or hepatic HYAL1 activity as a therapeutic strategy for managing excessive gluconeogenesis in insulin-resistant conditions, such as type 2 diabetes.展开更多
Dioxin is a highly toxic and caustic substance,which widely existed in the atmosphere,soil and water with tiny particles.Dioxin pollution has become a major problem that concerns the survival of mankind,which must be ...Dioxin is a highly toxic and caustic substance,which widely existed in the atmosphere,soil and water with tiny particles.Dioxin pollution has become a major problem that concerns the survival of mankind,which must be strictly controlled.The bond length,bond angle,energy,dipole moment,orbital energy level distribution of dioxin under the external field are investigated using DFT(density functional theory)on basis set level of B3LYP/6-31G(d,p).The results indicate that with the increase of the electric field,the length of one Carbon-Oxygen bond increases while another Carbon-Oxygen bond decreases.The energy gradually decreases with the electric field,while the change of the dipole moment has an opposite trend.In the infrared spectra,the vibration frequency decreases with the electric field increasing and shows an obvious red shift.Moreover,the ultraviolet-visible absorption spectra under different electric fields are analyzed with TD-DFT(time-dependent density functional theory)method.The wavelength of the strongest absorption peak increases and occurs red shift with the increase of the electric field.All the above results can provide reference for further research on the properties of dioxin under different external electric field.展开更多
Heavy metal pollution is a worldwide problem with many associated health risks, including bone loss, kidney damage, and several forms of cancer. There is a great need of bioremediation of these toxic metals from the e...Heavy metal pollution is a worldwide problem with many associated health risks, including bone loss, kidney damage, and several forms of cancer. There is a great need of bioremediation of these toxic metals from the environment, as well as implementing a monitoring system to control the spreading pollution. This study focuses on the bioremediation potential of Rhodobacter sphaeroides in the presence of the toxic gold chloride (AuCl3). Growth characteristics of the bacterial cells exposed to a range of toxic gold concentrations were analyzed through the growth kinetics and the colony forming units under aerobic, photosynthetic, and anaerobic growth conditions. The localization of the gold particles within two cellular fractions, cytoplasm and the plasma membrane, are analyzed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Results of this study demonstrated the photosynthetic growth condition as best suited for the metal tolerance, compared to the aerobic and anaerobic growth conditions. Results also revealed the overall accumulation and localization of gold particles, while not different between the membrane and the cytoplasmic fractions increased at different concentrations of the gold contamination. The results of the localization under photosynthetic growth condition revealed the accumulation reached the highest very quickly, and an overall shift in localization of the gold particles from an equal distribution to an increase within the membrane fraction at the highest concentrations of gold contamination. The localization of the gold particles was validated by Transmission Electron Microscopy (TEM) where the results confirmed the increase in accumulation within the membrane, and photosynthetic membranes, of R. sphaeroides.展开更多
There is a worldwide distribution of heavy metal pollution that can be managed with a bioremediation approach using microorganisms. Several bacterial species belonging to the Proteobacteria have been shown to tolerate...There is a worldwide distribution of heavy metal pollution that can be managed with a bioremediation approach using microorganisms. Several bacterial species belonging to the Proteobacteria have been shown to tolerate heavy metal stress, including toxic salts of noblemetals. Rhodobacter sphaeroides, a model bacterium has previously been utilized for bioremediation studies. A bioinformatics approach was employed here to identify the distribution of genes associated with heavy metal tolerance among the sequenced bacterial genomes currently available on the NCBI database. The distribution of these genes among different groups of bacteria and the Cluster of Orthologous Groups (COGs) were further characterized. A total of 170,000 heavy metal related genes were identified across all bacterial species, with a majority of the genes found in Proteobacteria (46%) and Terrabacteria (39%). Analysis of COGs revealed that the majority of heavy metal related genes belong to metabolism (COG 3), including ionic transport, amino acid biosynthesis, and energy production.展开更多
Alcoholic liver disease(ALD)encompasses a range of conditions resulting from prolonged and excessive alcohol consumption,causing liver damage such as alcoholic fatty liver,inflammation,fibrosis,and cirrhosis.Alcohol c...Alcoholic liver disease(ALD)encompasses a range of conditions resulting from prolonged and excessive alcohol consumption,causing liver damage such as alcoholic fatty liver,inflammation,fibrosis,and cirrhosis.Alcohol consumption contributes to millions of deaths each year.So far,the effective treatments for ALD are limited.To date,the most effective treatment for ALD is still prevention by avoiding excessive alcohol consumption,and only few specialized medicines are in the market for the treatment of patients suffering from ALD.Small molecules targeting various pathways implicated in ALD pathogenesis can potentially be used for effective therapeutics development.In this review,we provide a concise overview of the latest research findings on potential therapeutic targets,specifically emphasizing small-molecule interventions for the treatment and prevention of ALD.展开更多
基金supported by the USDA/ARS (cooperative agreement 3092-51000062)the NIH R01DK136532 and R01DK136619 to Y.Z.,the NIH R00AG068239,R01DK138035,and R01AG084646 to S.Z.,the NIH R00CA237618 and USDA/ARS (cooperative agreement 309251000-064) to X.G.+2 种基金the CPRIT Scholar in Cancer Research (RR210029) to D.G.supported by the CPRIT Core Facility Support Award RP210227 “Proteomic and Metabolomic Core Facility”,the NCI Cancer Center Support Grant P30CA125123,the NIH R01CA220297 and R01CA216426the intramural funds from the Dan L.Duncan Cancer Center (DLDCC) at the Baylor College of Medicine。
文摘Hepatic gluconeogenesis is a critical process that generates glucose from non-carbohydrate precursors during fasting to support vital organs like the brain and red blood cells. Postprandially, this process is rapidly suppressed to allow for glucose storage as glycogen and lipids in the liver. Failure to suppress gluconeogenesis after meals leads to elevated postprandial glucose levels, a key feature of type 2 diabetes. This dynamic switch is regulated by insulin and glucagon, but insulin resistance impairs this regulation. In this study, we identified a novel mechanism involving postprandial circulating hyaluronan(HA) and lysosomal hyaluronidase-1(HYAL1) that suppresses hepatic gluconeogenesis by rewiring hepatic metabolism and mitochondrial function. Hyal1 knockout(Hyal1 KO) mice exhibited increased gluconeogenesis, while liver-specific Hyal1 overexpression(Liv-Hyal1) mice showed reduced gluconeogenic activity. Transcriptomic analysis revealed minimal changes in liver gene expression due to Hyal1 deletion, but metabolomic profiling demonstrated that Hyal1 overexpression mitigated high-fat diet(HFD)-induced elevations in gluconeogenic pathway metabolites. Mechanistically, HYAL1-mediated HA digestion activates a feedback loop in HA synthesis, repartitioning the cellular uridine diphospho-N-acetyl-D-glucosamine(UDP-Glc NAc) pool. This reduces O-linked N-acetylglucosamine modification(O-Glc NAcylation) of mitochondrial ATP synthase subunits, decreasing ATP production and suppressing gluconeogenesis. Importantly, this pathway remains intact in the livers of HFD-fed, insulin-resistant mice. In summary, our findings reveal a new postprandial mechanism for regulating hepatic gluconeogenesis, highlighting the potential of enhancing postprandial HA levels or hepatic HYAL1 activity as a therapeutic strategy for managing excessive gluconeogenesis in insulin-resistant conditions, such as type 2 diabetes.
基金National Key R&D Program of China(2017YFC0212700)National Natural Science Foundation of China(11304157)+1 种基金“Six Talent Peaks”project in Jiangsu Province(2015-JNHB-011)College Students’Practice Innovation Training Program of Nuist(201810300033Z)
基金The project is supported by Natural Science Foundation of Xinjiang(No.2017D01B36).
文摘Dioxin is a highly toxic and caustic substance,which widely existed in the atmosphere,soil and water with tiny particles.Dioxin pollution has become a major problem that concerns the survival of mankind,which must be strictly controlled.The bond length,bond angle,energy,dipole moment,orbital energy level distribution of dioxin under the external field are investigated using DFT(density functional theory)on basis set level of B3LYP/6-31G(d,p).The results indicate that with the increase of the electric field,the length of one Carbon-Oxygen bond increases while another Carbon-Oxygen bond decreases.The energy gradually decreases with the electric field,while the change of the dipole moment has an opposite trend.In the infrared spectra,the vibration frequency decreases with the electric field increasing and shows an obvious red shift.Moreover,the ultraviolet-visible absorption spectra under different electric fields are analyzed with TD-DFT(time-dependent density functional theory)method.The wavelength of the strongest absorption peak increases and occurs red shift with the increase of the electric field.All the above results can provide reference for further research on the properties of dioxin under different external electric field.
文摘Heavy metal pollution is a worldwide problem with many associated health risks, including bone loss, kidney damage, and several forms of cancer. There is a great need of bioremediation of these toxic metals from the environment, as well as implementing a monitoring system to control the spreading pollution. This study focuses on the bioremediation potential of Rhodobacter sphaeroides in the presence of the toxic gold chloride (AuCl3). Growth characteristics of the bacterial cells exposed to a range of toxic gold concentrations were analyzed through the growth kinetics and the colony forming units under aerobic, photosynthetic, and anaerobic growth conditions. The localization of the gold particles within two cellular fractions, cytoplasm and the plasma membrane, are analyzed using Inductively Coupled Plasma Optical Emission Spectroscopy (ICP-OES). Results of this study demonstrated the photosynthetic growth condition as best suited for the metal tolerance, compared to the aerobic and anaerobic growth conditions. Results also revealed the overall accumulation and localization of gold particles, while not different between the membrane and the cytoplasmic fractions increased at different concentrations of the gold contamination. The results of the localization under photosynthetic growth condition revealed the accumulation reached the highest very quickly, and an overall shift in localization of the gold particles from an equal distribution to an increase within the membrane fraction at the highest concentrations of gold contamination. The localization of the gold particles was validated by Transmission Electron Microscopy (TEM) where the results confirmed the increase in accumulation within the membrane, and photosynthetic membranes, of R. sphaeroides.
文摘There is a worldwide distribution of heavy metal pollution that can be managed with a bioremediation approach using microorganisms. Several bacterial species belonging to the Proteobacteria have been shown to tolerate heavy metal stress, including toxic salts of noblemetals. Rhodobacter sphaeroides, a model bacterium has previously been utilized for bioremediation studies. A bioinformatics approach was employed here to identify the distribution of genes associated with heavy metal tolerance among the sequenced bacterial genomes currently available on the NCBI database. The distribution of these genes among different groups of bacteria and the Cluster of Orthologous Groups (COGs) were further characterized. A total of 170,000 heavy metal related genes were identified across all bacterial species, with a majority of the genes found in Proteobacteria (46%) and Terrabacteria (39%). Analysis of COGs revealed that the majority of heavy metal related genes belong to metabolism (COG 3), including ionic transport, amino acid biosynthesis, and energy production.
基金supported by the National Institute of Diabetes and Digestive and Kidney(R01-DK121970)to Dr.Feng Li.
文摘Alcoholic liver disease(ALD)encompasses a range of conditions resulting from prolonged and excessive alcohol consumption,causing liver damage such as alcoholic fatty liver,inflammation,fibrosis,and cirrhosis.Alcohol consumption contributes to millions of deaths each year.So far,the effective treatments for ALD are limited.To date,the most effective treatment for ALD is still prevention by avoiding excessive alcohol consumption,and only few specialized medicines are in the market for the treatment of patients suffering from ALD.Small molecules targeting various pathways implicated in ALD pathogenesis can potentially be used for effective therapeutics development.In this review,we provide a concise overview of the latest research findings on potential therapeutic targets,specifically emphasizing small-molecule interventions for the treatment and prevention of ALD.
