Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate...Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWlISNF chromatin.remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological sigrials. The ATP-dependent SWl/SNF ing complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different m^abolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.展开更多
Type 2 diabetes(T2D)has become a common chronic disease worldwide.Pancreaticβcell dysfunction,together with insulin resistance,is among the main causes for the pathogenesis of T2D.However,the dynamic changes in the n...Type 2 diabetes(T2D)has become a common chronic disease worldwide.Pancreaticβcell dysfunction,together with insulin resistance,is among the main causes for the pathogenesis of T2D.However,the dynamic changes in the number and function ofβcells and the molecular mechanism of irreversible damage in the pathogenesis of T2D are still unclear.A thorough analysis of the mechanism underlyingβcell dysfunction will provide a theoretical basis and molecular targets for the development of new and more effective individualized therapies for diabetes.展开更多
Valosin-containing protein （VCP） is a type-II adenosine triphosphatase （ATPase） wih extensive biological function in organisms. Silkworm is the second in- sect model for genetic studies and a bioreactor for protei...Valosin-containing protein （VCP） is a type-II adenosine triphosphatase （ATPase） wih extensive biological function in organisms. Silkworm is the second in- sect model for genetic studies and a bioreactor for proteinaceous drugs and biomaterials. In this paper, a new VCP-like gene was amplified from the fat body of silkworm follow- ing genome prediction and spliced expressed sequence tag sequences, using both reverse transcription polymerase chain reaction （RT-PCR） and 3＇-RACE （rapid amplification of complementary DNA ends） methods. Bioinformatical analysis showed that the translated amino acid sequence contained a highly conserved domain of VCPs similar to that of many insects. This domain consists of the conserved structure motifs of the ATP binding site and the catalytical center, which is closely related to the insect VCPs in a phylogenetic tree. The silkworm VCP-like gene was successfully inserted into the plasmid and transformed into Escherichia coli cells to express VCP-like protein with ATPase activity. The expression of silkworm VCP-like protein was also confirmed by Western blotting and mass spectromet- ric analyses. Distribution of the VCP-like gene in various tissues of the silkworm was also studied by real-time PCR. Results showed that the messenger RNA （mRNA） of VCP-like protein is widely expressed in fat body, reproductive organs （testis or ovary）, silk gland, head, Malpighian tubule, epidermis and midgut. Among them, fat body has the highest mRNA expression level of the VCP-like gene, while the midgut has the lowest expression level. This study provides groundwork for further study on the structure and function of the new VCP-like protein.展开更多
基金This work was supported by the National Natural Science Foundation of China （Grant No. 81670740）, the Thousand Young Talents Plan of China, and the National Key Research and Development Programme of China （No. 2016YFC1305303） to Z.X.M. by National Natural Science Foundation of China （Grant Nos. 81570759 and 81270938）, National Key Research and Development Programme of China （No. 2016YFC1305301）, Zhejiang Provincial Key Science and Technol- ogy Project （No. 2014C03045-2）, Key Disciplines of Medicine （Innovation discipline,11-CX24） to J.F. and by NIH grant （No. DKl12800） to J.D.L.
文摘Metabolic syndrome has become a global epidemic that adversely affects human health. Both genetic and environmental factors contribute to the pathogenesis of metabolic disorders; however, the mechanisms that integrate these cues to regulate metabolic physiology and the development of metabolic disorders remain incompletely defined. Emerging evidence suggests that SWlISNF chromatin.remodeling complexes are critical for directing metabolic reprogramming and adaptation in response to nutritional and other physiological sigrials. The ATP-dependent SWl/SNF ing complexes comprise up to 11 subunits, among which the BAF60 subunit serves as a key link between the core complexes and specific transcriptional factors. The BAF60 subunit has three members, BAF60a, b, and c. The distinct tissue distribution patterns and regulatory mechanisms of BAF60 proteins confer each isoform with specialized functions in different m^abolic cell types. In this review, we summarize the emerging roles and mechanisms of BAF60 proteins in the regulation of nutrient sensing and energy metabolism under physiological and disease conditions.
基金This work was supported inpart by the National Natural Science Foundation of China(91857110,81722012,81670740,82070805,81870535,and 31870855)the National Key Research and Development Programme of China(2018YFA0800403,2021YFC20701903,and 2020YFA0803704)+3 种基金Zhejiang Provincial Natural Science Foundation of China(LZ21Ho70001)the Construction Fund of Key Medical Disciplines of Hangzhou(0020200055)the Innovative Instituteof Basic Medical Sciences of Zhejiang Universitythe Fundamental Research Funds for the Central Universities.
文摘Type 2 diabetes(T2D)has become a common chronic disease worldwide.Pancreaticβcell dysfunction,together with insulin resistance,is among the main causes for the pathogenesis of T2D.However,the dynamic changes in the number and function ofβcells and the molecular mechanism of irreversible damage in the pathogenesis of T2D are still unclear.A thorough analysis of the mechanism underlyingβcell dysfunction will provide a theoretical basis and molecular targets for the development of new and more effective individualized therapies for diabetes.
文摘Valosin-containing protein （VCP） is a type-II adenosine triphosphatase （ATPase） wih extensive biological function in organisms. Silkworm is the second in- sect model for genetic studies and a bioreactor for proteinaceous drugs and biomaterials. In this paper, a new VCP-like gene was amplified from the fat body of silkworm follow- ing genome prediction and spliced expressed sequence tag sequences, using both reverse transcription polymerase chain reaction （RT-PCR） and 3＇-RACE （rapid amplification of complementary DNA ends） methods. Bioinformatical analysis showed that the translated amino acid sequence contained a highly conserved domain of VCPs similar to that of many insects. This domain consists of the conserved structure motifs of the ATP binding site and the catalytical center, which is closely related to the insect VCPs in a phylogenetic tree. The silkworm VCP-like gene was successfully inserted into the plasmid and transformed into Escherichia coli cells to express VCP-like protein with ATPase activity. The expression of silkworm VCP-like protein was also confirmed by Western blotting and mass spectromet- ric analyses. Distribution of the VCP-like gene in various tissues of the silkworm was also studied by real-time PCR. Results showed that the messenger RNA （mRNA） of VCP-like protein is widely expressed in fat body, reproductive organs （testis or ovary）, silk gland, head, Malpighian tubule, epidermis and midgut. Among them, fat body has the highest mRNA expression level of the VCP-like gene, while the midgut has the lowest expression level. This study provides groundwork for further study on the structure and function of the new VCP-like protein.
