Excessive supply of glucose elicits an NF-κB2-dependent glycolysis in lactating goat mammary glands.
During lactation, an improper glucose supply often threatens mammary gland (MG) health. However, information is limited on the metabolic trajectories and molecules that regulate lactating MGs with an excessive glucose supply. Based on the network analysis of transcriptome and microRNAs, we found that the oversupply of glucose-induced severe glucose metabolic disorders in MGs of lactating goats, shifting lactose synthesis to acute fermentative glycolysis which caused increased flux of glucose metabolism into lactate. Moreover, NF-κB2 played a key role in regulating glycolysis, exhibiting a metabolic shift when MGs had an excessive supply of glucose. In primary mammary epithelial cells, fermentative glycolysis, and intracellular concentration of reactive oxygen species (ROS) were reduced by ganoderic acid A through blocking NF-κB2, while activation of NF-κB2 with phorbol myristate acetate (PMA) upregulated fermentative glycolysis and increased cellular ROS accumulation under excessive glucose. Thus, we established an NF-κB2-targeting method to reform the metabolic shift toward glycolysis caused by glucose oversupply by integrating NF-κB2 blockade and intracellular ROS scavenging.
['Cai|Jie|J|', 'Wang|Diming|D|', 'Liang|Shulin|S|', 'Peng|Jinrong|J|', 'Zhao|Fengqi|F|', 'Liu|Jianxin|J|']
D000818:Animals D004847:Epithelial Cells D005260:Female D005947:Glucose D006019:Glycolysis D006041:Goats D007774:Lactation D007785:Lactose D008321:Mammary Glands, Animal D035683:MicroRNAs D008892:Milk D052003:NF-kappa B p52 Subunit D017382:Reactive Oxygen Species D059467:Transcriptome D015854:Up-Regulation
glycolysis lactation mammary gland transcriptome NF-κB coexpression