As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain uncle...As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear.Using the electron microscopy technology,along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays,we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells,accompanied by an increased total level of triglycerides.At the molecular level,the lipogenesis-associated mRNAs and proteins,including acetyl-CoA carboxylase,fatty acid synthase,stearoyl-CoA desaturase-1,peroxisome proliferator-activated receptor gamma,and CCAAT-enhancer-binding proteins,increased significantly via the AMP-activated protein kinase(AMPK)-mammalian target of rapamycin(mTOR)signaling regulation in both in vitro and in vivo studies.Furthermore,the immunofluorescence results also showed the robust lipogenesis induced by BPF,evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei.To investigate the intervention strategies for BPF-induced NAFLD-like changes,we demonstrated that bellidifolin,isolated and purified from Swertia chirayita,significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins.Therefore,the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells,while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.展开更多
Ruminant livestock provide a rich source of products,such as meat,milk,and wool,and play a critical role in global food security and nutrition.Over the past few decades,genomic studies of ruminant livestock have provi...Ruminant livestock provide a rich source of products,such as meat,milk,and wool,and play a critical role in global food security and nutrition.Over the past few decades,genomic studies of ruminant livestock have provided valuable insights into their domestication and the genetic basis of economically important traits,facilitating the breeding of elite varieties.In this review,we summarize the main advancements for domestic ruminants in reference genome assemblies,population genomics,and the identification of functional genes or variants for phenotypic traits.These traits include meat and carcass quality,reproduction,milk production,feed efficiency,wool and cashmere yield,horn development,tail type,coat color,environmental adaptation,and disease resistance.Functional genomic research is entering a new era with the advancements of graphical pangenomics and telomere-to-telomere(T2T)gap-free genome assembly.These advancements promise to improve our understanding of domestication and the molecular mechanisms underlying economically important traits in ruminant livestock.Finally,we provide new perspectives and future directions for genomic research on ruminant genomes.We suggest how ever-increasing multiomics datasets will facilitate future studies and molecular breeding in livestock,including the potential to uncover novel genetic mechanisms underlying phenotypic traits,to enable more accurate genomic prediction models,and to accelerate genetic improvement programs.展开更多
基金supported by the Natural Science Foundation of the Jiangsu Higher Education Institutions of China(Grant No.21KJA330002)Natural Science Foundation of Jiangsu Province(Grant No.BK20211252)+3 种基金Young and Middle-aged Academic Leaders of the"Blue Project"in Jiangsu Universities(2022-2)Jiangsu Health and Family Planning Commission Medical Research Program(Grant No.Z2018035)Project of Public Health Research Center of Jiangnan University(Grant No.JUPH201842)Natural Science Foundation of Nanjing University of Chinese Medicine(Grant No.XZR2020021).
文摘As a potential endocrine-disrupting chemical,bisphenol F(BPF)may cause nonalcoholic fatty liver disease(NAFLD)-like changes,but the mechanisms under its pathogenesis as well as the intervention strategies remain unclear.Using the electron microscopy technology,along with LipidTOX Deep Red neutral and Bodipy 493/503 staining assays,we observed that BPF treatment elicited a striking accumulation of lipid droplets in HepG2 cells,accompanied by an increased total level of triglycerides.At the molecular level,the lipogenesis-associated mRNAs and proteins,including acetyl-CoA carboxylase,fatty acid synthase,stearoyl-CoA desaturase-1,peroxisome proliferator-activated receptor gamma,and CCAAT-enhancer-binding proteins,increased significantly via the AMP-activated protein kinase(AMPK)-mammalian target of rapamycin(mTOR)signaling regulation in both in vitro and in vivo studies.Furthermore,the immunofluorescence results also showed the robust lipogenesis induced by BPF,evident in its ability to promote the translocation of sterol regulatory element-binding protein-1c from the cytoplasm to the nuclei.To investigate the intervention strategies for BPF-induced NAFLD-like changes,we demonstrated that bellidifolin,isolated and purified from Swertia chirayita,significantly attenuated BPF-induced lipid droplet deposition in HepG2 cells and NAFLD-like changes in mice by blocking the expression of lipogenesis-associated proteins.Therefore,the present study elucidates the mechanisms underlying the BPF-induced lipid accumulation in HepG2 cells,while also highlighting the potential of bellidifolin to mitigate BPF-induced NAFLD-like changes.
基金supported by the Project of Northern Agriculture and Livestock Husbandry Technology Innovation Center,Chinese Academy of Agricultural Sciences(BFGJ2022002)the National Key Research and Development Program of China(2021YFD1200900,2023YFF1001003,and 2023YFF1000900)+3 种基金Biological Breeding-National Science and Technology Major Project(2023ZD0407106)the National Natural Science Foundation of China(32102511,31661143014,31972527,32320103006,and 32272845)Chinese Universities Scientific Fund(2024TC162)National High Level Hospital Clinical Research Funding(2023-NHLHCRF-YXHZ-TJMS-09)。
文摘Ruminant livestock provide a rich source of products,such as meat,milk,and wool,and play a critical role in global food security and nutrition.Over the past few decades,genomic studies of ruminant livestock have provided valuable insights into their domestication and the genetic basis of economically important traits,facilitating the breeding of elite varieties.In this review,we summarize the main advancements for domestic ruminants in reference genome assemblies,population genomics,and the identification of functional genes or variants for phenotypic traits.These traits include meat and carcass quality,reproduction,milk production,feed efficiency,wool and cashmere yield,horn development,tail type,coat color,environmental adaptation,and disease resistance.Functional genomic research is entering a new era with the advancements of graphical pangenomics and telomere-to-telomere(T2T)gap-free genome assembly.These advancements promise to improve our understanding of domestication and the molecular mechanisms underlying economically important traits in ruminant livestock.Finally,we provide new perspectives and future directions for genomic research on ruminant genomes.We suggest how ever-increasing multiomics datasets will facilitate future studies and molecular breeding in livestock,including the potential to uncover novel genetic mechanisms underlying phenotypic traits,to enable more accurate genomic prediction models,and to accelerate genetic improvement programs.