Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed tha...Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 (UCP2) and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue (WAT), suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue (BAT), suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.展开更多
Caveolin-2,a protein about 20 kD,is a major component of the inner surface of caveolae,small invaginations of the plasma membrane.Similar with caveolin-1 and caveolin-3,it serves as a protein marker of caveolae.Caveol...Caveolin-2,a protein about 20 kD,is a major component of the inner surface of caveolae,small invaginations of the plasma membrane.Similar with caveolin-1 and caveolin-3,it serves as a protein marker of caveolae.Caveolin-1 and-2 are located next to each other at 7q31.1 on human chromosome,the proteins encoded are co-localized and form a stable hetero-oligomeric complex,distributing similarly in tissue and cultured cells.Caveolin-3 is located on different chromosomes but confirmed to interact with caveolin-2.Caveolin-2 is similar to caveolin-1 in many respects but differs from the latter in functional domains,especially in G-protein binding domain and caveolin scaffolding domain.The mRNAs of both caveolin-1 and caveolin-2 are most abundantly expressed in white adipose tissue and are induced during differentiation of 3T3-L1 cells to adipocytes.Caveolin-2-deficinet mice demonstrate clear pulmonary defects,with little or no change in caveolin-1 expression and caveolae formation,suggesting that caveolin-2 plays a selective role in lung functions.Caveolin-2 is also involved in lipid metabolism and human cancers.展开更多
This study was conducted to evaluate the effects of dietary lipid sources on the growth performance and fatty acid composition of the swimming crab, P ortunus trituberculatus. Four isonitrogenous and isoenergetic expe...This study was conducted to evaluate the effects of dietary lipid sources on the growth performance and fatty acid composition of the swimming crab, P ortunus trituberculatus. Four isonitrogenous and isoenergetic experimental diets were formulated to contain four separate lipid sources, including fish, soybean, rapeseed, and linseed oils(FO, SO, RO, and LO, respectively). With three replicates of 18 crabs each for each diet, crabs(initial body weight, 17.00 ±0.09 g) were fed twice daily for 8 weeks. There were no significant differences among these groups in terms of weight gain, specific growth rate, and hepatosomatic index. However, the RO groups' survival rate was significantly lower than FO groups. The feed conversion and protein efficiency ratios of RO groups were poorer than other groups. The proximate compositions of whole body and hepatopancreas were significantly affected by these dietary treatments. Tissue fatty acid composition mainly reflected dietary fatty acid compositions. Crabs fed FO diets exhibited significantly higher arachidonic, eicosapentaenoic, and docosahexaenoic acid contents in muscle and hepatopancreas compared with VO crabs. Linoleic, oleic, and linolenic acids in muscle and hepatopancreas were the highest in the SO, RO, and LO groups, respectively. The present study suggested that SO and LO could substitute for FO in fishmeal-based diets for swimming crabs, without affecting growth performance and survival.展开更多
Objective To investigate protective effects of electroacupuncture on injury of lipid peroxidation-induced by liver ischemia in rats with sepsis.Methods Forty-eight male SD rats were subjected to sepsis by cecal ligati...Objective To investigate protective effects of electroacupuncture on injury of lipid peroxidation-induced by liver ischemia in rats with sepsis.Methods Forty-eight male SD rats were subjected to sepsis by cecal ligation and puncture (CLP),and were randomly divided into a sham operation group (group A),a CLP model group (group B),a CLP model plus electroacupuncture (EA) at Zúsānlǐ (足三里 ST 36) group (group C),a CLP model plus electroacupuncture at a sham acupoint group (group D),a CLP model with vagotomy group (group E) and a CLP model plus electroacupuncture group after vagotomy (group F),with 8 rats in each group.CLP was performed after abdominal vagotomy in group E and group F.EA (2 mA,2/100 Hz) was applied at bilateral "Zúsānlǐ" (足三里 ST 36) in group C and group F,and at sham acupoints in group D,respectively,for 1 hour.The hepatic blood flow (HBF) was detected by a laser-doppler flowmetry at 6 hours after CLP.The activity of plasma alanine transarninase (ALT) was determined;contents of hepatic malondialdehyde (MDA),activity of xanthine oxidase (XOD) and the rate of water content in the hepati tissue were assessed,respectively.Results Hepatic blood flow was (56.97±11.95) U in group C,which was significantly lower than (80.12± 19.57) U shown in group A,but higher than (42.61±10.97) U in group B,(44.53±9.23) U in group D,(30.05 ±4.46) U in group E and (30.46±6.38) U in group F (all P0.05) at 6 hours after CLP.Meanwhile,the levels of MDA,XOD,ALT and hepatic water content in group C were all significantly higher than those in group A,but lower than those in the other four groups (all P0.05).The levels of MDA,XOD,ALT and hepatic water content in group E and group F were all significantly higher than those in group D (all P0.05),while their hepatic blood flow were lower than that in group D (both P0.05),and no significant differences were found in all the indices mentioned above between group E and group F (all P0.05).Conclusion Electroacupuncture at "Zúsānlǐ" (足三里 ST 36) can improve hepatic ischemia,inhibit lipid peroxidation and alleviate hepatic edema and dysfunction in septic rats,which might be related with the completeness of vagus nerves.展开更多
Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular or...Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular organelle responsible for lipid storage.We previously observed that Fsp27,a member of the CIDE family proteins,is localized to LD-contact sites and promotes atypical LD fusion and growth.Cidea,a close homolog of Fsp27,is expressed at high levels in brown adipose tissue.However,the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown.Here,we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth.Next,we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype.In addition,Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold.Furthermore,we observed that the brown and white adipose tissues of Cidea/Fsp27double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27single deficient mice.Overall,these data reveal an important role of Cidea in controlling lipid droplet fusion,lipid storage in brown and white adipose tissue,and the development of obesity.展开更多
We investigated the bio-distributions of [125 I]Spiro-I formulated in sterically stabilized liposomes (SSL) or targeted liposomes (SSTL) in mice,especially their brain uptake.The [125 I]Spiro-I liposomes were prep...We investigated the bio-distributions of [125 I]Spiro-I formulated in sterically stabilized liposomes (SSL) or targeted liposomes (SSTL) in mice,especially their brain uptake.The [125 I]Spiro-I liposomes were prepared by film-ultrasound dispersion method.Cereport (RMP-7) was covalently conjugated with DSPE-PEG,which was attached to the surface of SSL to form SSTL.The encapsulation efficiencies (ee%) of [125 I]Spiro-I-SSL and [125 I]Spiro-I-SSTL were 97.47%±4.01% and 93.02%±2.98%,respectively.The average particle sizes were (66.47±0.76) nm and (71.40±0.45) nm,respectively.After intravenous administration,[125 I]Spiro-I was quickly eliminated from blood.SSL could prolong the retention time of [125 I]Spiro-I in blood and SSTL improved its brain uptake.The AUC of [125 I]Spiro-I-SSTL in brain was increased by 1.52 times as compared to [125 I]Spiro-I,indicating that SSTL could be used for the formulation of [125 I]Spiro-I for the imaging of central nervous system (CNS).展开更多
Objective: To differentiate rat adipose tissue-derived mesenchymal stem cells (ADSCs) into cells with a nucleus pulposus-like phenotype in vitro, so as to lay a foundation for the cell-based transplantation therapy...Objective: To differentiate rat adipose tissue-derived mesenchymal stem cells (ADSCs) into cells with a nucleus pulposus-like phenotype in vitro, so as to lay a foundation for the cell-based transplantation therapy of degenerated intervertebral discs. Methods: Rat ADSCs were isolated only from the subcutaneous inguinal region and purified by limited dilution. ADSCs of the third passages were analyzed by fluorescence activated cell sorter (FACS) to detect the cell surface markers (Sca-1, CD44, CD45, CDI lb). To induce ADSCs to- wards a nucleus pulposus-like phenotype, ADSCs were immobilized in 3-dimensional alginate hydrogels and cultured in an inducing medium containing transforming growth factor-beta1 (TGF- β1) under hypoxia (2% O2), while control groups under normoxia (21% O2) in alginate beads in medium with or without the presence of TGF-β 1. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was carried out to evaluate phenotypic and biosynthetic activities in the process of differentiation. Meanwhile, Alcian blue staining were used to detect the formation of sulfated glycosaminoglycans (GAGs) in the differentiated cells. Results: The purified ADSCs were fibroblast-like and proliferated rapidly in vitro. The flow cytometry showed that ADSCs were positive for Sca-1 and CD44, negative for CD45 and CD11b. The results of RT-PCR manifested that the gene expressions of Sox-9, aggrecan and collagen Ⅱ, which were chondrocyte specific, were upregulated in medium containing TGF-β1 under hypoxia (2% O2). Likewise, gene expression of HIF-1 a, which was characteristics of in- tervertebral discs, was also upregulated. Simultaneously, Alcian blue staining exhibited the formation of many GAGs. Conclusions: The approach in our experiment is a simple and effective way to acquire a large quantity of homogenous ADSCs. Rat ADSCs can be differentiated into nucleus pulposus-like cells. ADSCs may replace bone marrow mesenchymal stem cells as a new kind of seed cells in regeneration of degenerated intervertebral discs using cell transolantation therarw.展开更多
文摘Activating transcription factor 4 (ATF4) has been shown to play key roles in many physiological processes. There are no reports, however, demonstrating a direct link between ATF4 and lipid metabolism. We noticed that Atf4- deficient mice are lean, suggesting a possible role for ATF4 in regulating lipid metabolism. The goal of our current study is to investigate the involvement of ATF4 in lipid metabolism and elucidate the underlying mechanisms. Studies using Atf4-deficient mice revealed increased energy expenditure, as measured by oxygen consumption. These mice also showed increases in lipolysis, expression of uncoupling protein 2 (UCP2) and p-oxidation genes and decreases in expression of lipogenic genes in white adipose tissue (WAT), suggesting increased utilization and decreased synthesis of fatty acids, respectively. Expression of UCP1, 2 and 3 was also increased in brown adipose tissue (BAT), suggesting increased thermogenesis. The effect of ATF4 deletion on expression of UCPs in BAT suggests that increased thermogenesis may underlie increased energy expenditure. Thus, our study identifies a possible new function for ATF4 in regulating lipid metabolism and thermogenesis.
基金Supported by National Basic Research Program of China (973 Program) (2004CB518602,2006CB503909)National High Technology Research and Development Program of China (863 Program) (2009AA02Z192)
文摘Caveolin-2,a protein about 20 kD,is a major component of the inner surface of caveolae,small invaginations of the plasma membrane.Similar with caveolin-1 and caveolin-3,it serves as a protein marker of caveolae.Caveolin-1 and-2 are located next to each other at 7q31.1 on human chromosome,the proteins encoded are co-localized and form a stable hetero-oligomeric complex,distributing similarly in tissue and cultured cells.Caveolin-3 is located on different chromosomes but confirmed to interact with caveolin-2.Caveolin-2 is similar to caveolin-1 in many respects but differs from the latter in functional domains,especially in G-protein binding domain and caveolin scaffolding domain.The mRNAs of both caveolin-1 and caveolin-2 are most abundantly expressed in white adipose tissue and are induced during differentiation of 3T3-L1 cells to adipocytes.Caveolin-2-deficinet mice demonstrate clear pulmonary defects,with little or no change in caveolin-1 expression and caveolae formation,suggesting that caveolin-2 plays a selective role in lung functions.Caveolin-2 is also involved in lipid metabolism and human cancers.
基金Supported by the Agriculture Science Technology Achievement Transformation Fund(No.2014GB2C22015)the Public Projects of Zhejiang Province(Nos.2013C32037,2013C31032)+3 种基金the Zhejiang Major Special Program of Breeding(No.2012C12907-3)the Ningbo Innovation and Entrepreneurship Project(No.2014C92011)the Zhejiang Provincial Oceanic and Fishery Bureau ProjectZhoushan Science and Technology Bureau Project(No.2013C41007)
文摘This study was conducted to evaluate the effects of dietary lipid sources on the growth performance and fatty acid composition of the swimming crab, P ortunus trituberculatus. Four isonitrogenous and isoenergetic experimental diets were formulated to contain four separate lipid sources, including fish, soybean, rapeseed, and linseed oils(FO, SO, RO, and LO, respectively). With three replicates of 18 crabs each for each diet, crabs(initial body weight, 17.00 ±0.09 g) were fed twice daily for 8 weeks. There were no significant differences among these groups in terms of weight gain, specific growth rate, and hepatosomatic index. However, the RO groups' survival rate was significantly lower than FO groups. The feed conversion and protein efficiency ratios of RO groups were poorer than other groups. The proximate compositions of whole body and hepatopancreas were significantly affected by these dietary treatments. Tissue fatty acid composition mainly reflected dietary fatty acid compositions. Crabs fed FO diets exhibited significantly higher arachidonic, eicosapentaenoic, and docosahexaenoic acid contents in muscle and hepatopancreas compared with VO crabs. Linoleic, oleic, and linolenic acids in muscle and hepatopancreas were the highest in the SO, RO, and LO groups, respectively. The present study suggested that SO and LO could substitute for FO in fishmeal-based diets for swimming crabs, without affecting growth performance and survival.
基金Supported by State Natural Sciences Foundation(NCFS):30672725Army Medical Health"11th Five-Year Plan"Special Subject:06Z055
文摘Objective To investigate protective effects of electroacupuncture on injury of lipid peroxidation-induced by liver ischemia in rats with sepsis.Methods Forty-eight male SD rats were subjected to sepsis by cecal ligation and puncture (CLP),and were randomly divided into a sham operation group (group A),a CLP model group (group B),a CLP model plus electroacupuncture (EA) at Zúsānlǐ (足三里 ST 36) group (group C),a CLP model plus electroacupuncture at a sham acupoint group (group D),a CLP model with vagotomy group (group E) and a CLP model plus electroacupuncture group after vagotomy (group F),with 8 rats in each group.CLP was performed after abdominal vagotomy in group E and group F.EA (2 mA,2/100 Hz) was applied at bilateral "Zúsānlǐ" (足三里 ST 36) in group C and group F,and at sham acupoints in group D,respectively,for 1 hour.The hepatic blood flow (HBF) was detected by a laser-doppler flowmetry at 6 hours after CLP.The activity of plasma alanine transarninase (ALT) was determined;contents of hepatic malondialdehyde (MDA),activity of xanthine oxidase (XOD) and the rate of water content in the hepati tissue were assessed,respectively.Results Hepatic blood flow was (56.97±11.95) U in group C,which was significantly lower than (80.12± 19.57) U shown in group A,but higher than (42.61±10.97) U in group B,(44.53±9.23) U in group D,(30.05 ±4.46) U in group E and (30.46±6.38) U in group F (all P0.05) at 6 hours after CLP.Meanwhile,the levels of MDA,XOD,ALT and hepatic water content in group C were all significantly higher than those in group A,but lower than those in the other four groups (all P0.05).The levels of MDA,XOD,ALT and hepatic water content in group E and group F were all significantly higher than those in group D (all P0.05),while their hepatic blood flow were lower than that in group D (both P0.05),and no significant differences were found in all the indices mentioned above between group E and group F (all P0.05).Conclusion Electroacupuncture at "Zúsānlǐ" (足三里 ST 36) can improve hepatic ischemia,inhibit lipid peroxidation and alleviate hepatic edema and dysfunction in septic rats,which might be related with the completeness of vagus nerves.
基金supported by grants from the National Basic Research Program(2013CB530602 and 2011CB910801 to Li Peng)the National Natural Science Foundation of China(30925017,31030038 and 90913024)the China Postdoctoral Science Foundation(2012M520249 and 2013T60103 to Zhou LinKang)
文摘Excess lipid storage in adipose tissue results in the development of obesity and other metabolic disorders including diabetes,fatty liver and cardiovascular diseases.The lipid droplet(LD)is an important subcellular organelle responsible for lipid storage.We previously observed that Fsp27,a member of the CIDE family proteins,is localized to LD-contact sites and promotes atypical LD fusion and growth.Cidea,a close homolog of Fsp27,is expressed at high levels in brown adipose tissue.However,the exact role of Cidea in promoting LD fusion and lipid storage in adipose tissue remains unknown.Here,we expressed Cidea in Fsp27-knockdown adipocytes and observed that Cidea has similar activity to Fsp27 in promoting lipid storage and LD fusion and growth.Next,we generated Cidea and Fsp27 double-deficient mice and observed that these animals had drastically reduced adipose tissue mass and a strong lean phenotype.In addition,Cidea/Fsp27 double-deficient mice had improved insulin sensitivity and were intolerant to cold.Furthermore,we observed that the brown and white adipose tissues of Cidea/Fsp27double-deficient mice had significantly reduced lipid storage and contained smaller LDs compared to those of Cidea or Fsp27single deficient mice.Overall,these data reveal an important role of Cidea in controlling lipid droplet fusion,lipid storage in brown and white adipose tissue,and the development of obesity.
基金National Basic Research Program of China (973 Program, Grant No. 2009CB930300)National Natural Science Foundation of China (Grant No.20501004 and 20871021)
文摘We investigated the bio-distributions of [125 I]Spiro-I formulated in sterically stabilized liposomes (SSL) or targeted liposomes (SSTL) in mice,especially their brain uptake.The [125 I]Spiro-I liposomes were prepared by film-ultrasound dispersion method.Cereport (RMP-7) was covalently conjugated with DSPE-PEG,which was attached to the surface of SSL to form SSTL.The encapsulation efficiencies (ee%) of [125 I]Spiro-I-SSL and [125 I]Spiro-I-SSTL were 97.47%±4.01% and 93.02%±2.98%,respectively.The average particle sizes were (66.47±0.76) nm and (71.40±0.45) nm,respectively.After intravenous administration,[125 I]Spiro-I was quickly eliminated from blood.SSL could prolong the retention time of [125 I]Spiro-I in blood and SSTL improved its brain uptake.The AUC of [125 I]Spiro-I-SSTL in brain was increased by 1.52 times as compared to [125 I]Spiro-I,indicating that SSTL could be used for the formulation of [125 I]Spiro-I for the imaging of central nervous system (CNS).
文摘Objective: To differentiate rat adipose tissue-derived mesenchymal stem cells (ADSCs) into cells with a nucleus pulposus-like phenotype in vitro, so as to lay a foundation for the cell-based transplantation therapy of degenerated intervertebral discs. Methods: Rat ADSCs were isolated only from the subcutaneous inguinal region and purified by limited dilution. ADSCs of the third passages were analyzed by fluorescence activated cell sorter (FACS) to detect the cell surface markers (Sca-1, CD44, CD45, CDI lb). To induce ADSCs to- wards a nucleus pulposus-like phenotype, ADSCs were immobilized in 3-dimensional alginate hydrogels and cultured in an inducing medium containing transforming growth factor-beta1 (TGF- β1) under hypoxia (2% O2), while control groups under normoxia (21% O2) in alginate beads in medium with or without the presence of TGF-β 1. Semiquantitative reverse transcription polymerase chain reaction (RT-PCR) was carried out to evaluate phenotypic and biosynthetic activities in the process of differentiation. Meanwhile, Alcian blue staining were used to detect the formation of sulfated glycosaminoglycans (GAGs) in the differentiated cells. Results: The purified ADSCs were fibroblast-like and proliferated rapidly in vitro. The flow cytometry showed that ADSCs were positive for Sca-1 and CD44, negative for CD45 and CD11b. The results of RT-PCR manifested that the gene expressions of Sox-9, aggrecan and collagen Ⅱ, which were chondrocyte specific, were upregulated in medium containing TGF-β1 under hypoxia (2% O2). Likewise, gene expression of HIF-1 a, which was characteristics of in- tervertebral discs, was also upregulated. Simultaneously, Alcian blue staining exhibited the formation of many GAGs. Conclusions: The approach in our experiment is a simple and effective way to acquire a large quantity of homogenous ADSCs. Rat ADSCs can be differentiated into nucleus pulposus-like cells. ADSCs may replace bone marrow mesenchymal stem cells as a new kind of seed cells in regeneration of degenerated intervertebral discs using cell transolantation therarw.