Cell-Intrinsic Glycogen Metabolism Supports Early Glycolytic Reprogramming Required for Dendritic Cell Immune Responses
Phyu M. Thwe,1,3 Leonard Pelgrom,2 Rachel Cooper,3 Saritha Beauchamp,3 Julie A. Reisz,4 Angelo D’Alessandro,4Bart Everts,2 and Eyal Amiel1,3,5,*
Cell Metabolism
This paper is about the nutrient homeostasis in DCs. It mainly identified a novel mechanism of metabolic regulation in DCs by which glucose- and glycogen-derived carbons preferentially contribute to distinct metabolic pathways. DCs are are canonical ‘‘professional antigen presenting cells’’ of the immune system and play a central role in regulating both innate and adaptive immune responses. Upon activated by stimulants, DCs undergo a immunometabolism reprogramming. But the the source of glucose supporting the earliest events in DC activation, namely whether glucose is sourced from the extracellular environment or from intracellular pools, has not been fully defined.In this paper the authors suggested that the DCs utilize intracellular glycogen reserves to fuel their metabolic needs during early immune activation and that glycogen metabolism is required by these cells to initiate proper immune effector responses.This paper offered a new and potential therapies to restore immune tolerance in chronic inflammatory and autoimmune diseases for their effective treatment. Firstly, they performed a nutrient screening assay using single-carbon-source defined media and found that DCs can catabolize both shortand long-chain glucose polymers and DCs express glycogen metabolic machinery and utilize cell-intrinsic glycogen metabolism upon activation. Plycogen phosphorylase inhibition impacts DCs survival in hypoglycemic conditions. Further study confirmed that intracellular glycogen stores are catabolized to support DCs effector function and glycogen metabolism preferentially supports early DC maturation. Finaly, they demonstrated that different from glucose- carbons, glycogen-derived carbons fuel both glycolytic reprogramming and mitochondrial respiration in activated DCs.
This paper provided a new insight into how metabolic pathways operate at a subcellular level, which may a new cell therapeutic strategy in the future.
https://doi.org/10.1016/j.cmet.2017.08.012
The FGF21-CCL11 Axis Mediates Beiging of White Adipose Tissues by Coupling Sympathetic Nervous System to Type 2 Immunity
Zhe Huang,1,2 Ling Zhong,1,2 Jimmy Tsz Hang Lee,1,2 Jialiang Zhang,1,2 Donghai Wu,4 Leiluo Geng,1,2 Yu Wang,1,3 Chi-Ming Wong,1,2,3,* and Aimin Xu1,2,3,5
Cell Metabolism
This paper focused on the role FGF21 in the beiging of white adipose tissues. FGF21 is also one of my interest molecules in my mind. Fibroblast growth factor 21 (FGF21), a member of the endocrine FGF subfamily, has pleiotropic effects on the regulation of energy homeostasis and insulin sensitivity via binding with its receptor complex beten FGF receptor-1 (FGFR1) and co-receptor b-Klotho (KLB).FGF21 also has a important role in immunoregulation .The liver and adipose tissues are the main resource of FGF21 in vivo. Generaly, FGF21 is a stress responsive hormone and its expression is markedly induced by a diverse range of physiological or pathological stresses. Global deletion of FGF21 in mice leads to impairments in cold-induced beiging of scWAT, while administration of recombinant FGF21 increases beiging of scWAT and total energy expenditure in mice. In this paper the author detected the FGF21 expression in different tissues at normal conditions or cold stimulation and found that FGF21 expression is selectively induced in thermogenic adipose depots(scWAT and BAT) by cold exposure. Using tissue-specific conditional knockout mice ,they demonstrated that adipose-specific FGF21 deficiency leads to impaired adaptation to cold environment . To investigate the mechanisms, firstly, they tested whether FGF21 directly promotes UCP1 induction in adipocytes and found that the effects of FGF21 on beiging of scWAT is not the direct induction of UCP1 in adipocytes. Then, they detected another important endocrine adiponectin and suggested that FGF21 may modulate the microenvironment required for beiging of scWAT, particularly type 2 immune cells and their secreted cytokines. Further study confirmed that adipose-derived FGF21 is required for cold-induced recruitment of eosinophils and M2 macrophages, and proliferation and commitment of adipocyte precursor cells in scWAT. Finally ,they focus on the mechanism of how FGF21 promotes recruitment of eosinophils into scWAT and conclude that CCL11 is a physiological mediator for cold-induced recruitment of eosinophils and beiging in scWAT and CCL 11 is obligatory for FGF21-mediated effects on beiging of scWAT during Cold simulation.
This paper provided a new insight into how how the immune system communicates with sympathetic nerves to control adaptive thermogenesis and suggested a new strategy for metabolic disease treatment.
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