Department of Biochemistry, Molecular Biology and Biophysics, The University of Minnesota, Minneapolis, MN 55455, USA.
Department of Food Science and Nutrition, The University of Minnesota, Minneapolis, MN 55455, USA.
Endocrinology. 2022 Aug 1;163(8). doi: 10.1210/endocr/bqac094.
Immune cells infiltrate adipose tissue as a function of age, sex, and diet, leading to a variety of regulatory processes linked to metabolic disease and dysfunction. Cytokines and chemokines produced by resident macrophages, B cells, T cells and eosinophils play major role(s) in fat cell mitochondrial functions modulating pyruvate oxidation, electron transport and oxidative stress, branched chain amino acid metabolism, fatty acid oxidation, and apoptosis. Indeed, cytokine-dependent downregulation of numerous genes affecting mitochondrial metabolism is strongly linked to the development of the metabolic syndrome, whereas the potentiation of mitochondrial metabolism represents a counterregulatory process improving metabolic outcomes. In contrast, inflammatory cytokines activate mitochondrially linked cell death pathways such as apoptosis, pyroptosis, necroptosis, and ferroptosis. As such, the adipocyte mitochondrion represents a major intersection point for immunometabolic regulation of central metabolism.
免疫细胞会随着年龄、性别和饮食的变化而浸润脂肪组织，导致与代谢疾病和功能障碍相关的各种调节过程。驻留巨噬细胞、B 细胞、T 细胞和嗜酸性粒细胞产生的细胞因子和趋化因子在调节丙酮酸氧化、电子传递和氧化应激、支链氨基酸代谢、脂肪酸氧化和细胞凋亡等方面发挥重要作用。事实上，细胞因子依赖性地下调许多影响线粒体代谢的基因与代谢综合征的发展密切相关，而线粒体代谢的增强则代表了一种改善代谢结果的对抗调节过程。相反，炎症细胞因子会激活与线粒体相关的细胞死亡途径，如细胞凋亡、细胞焦亡、坏死性凋亡和铁死亡。因此，脂肪细胞线粒体是中央代谢免疫代谢调节的一个主要交汇点。
