Abnormal histidine metabolism promotes macrophage lipid accumulation under Ox-LDL condition

• Published in: Biochemical and biophysical research communications Vol. 588; pp. 161 - 167
• Main Authors: Zhu, Baoling, Zhang, Zhiwei, Wang, Xiangfei, Zhang, Weiwei, Shi, Hongyu, Song, Zhifeng, Ding, Suling, Yang, Xiangdong
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 15.01.2022
• Subjects: Animals; Cholesterol - metabolism; Gene Expression Profiling; Gene Expression Regulation - drug effects; Histamine - deficiency; Histamine H1 receptor; Histidine - metabolism; Histidine decarboxylase; Lipid metabolism; Lipid Metabolism - drug effects; Lipid Metabolism - genetics; Lipoproteins, LDL - pharmacology; Macrophage; Macrophages - drug effects; Macrophages - metabolism; Male; Mice; Mice, Inbred C57BL; Mice, Transgenic; Receptors, Histamine - metabolism; Signal Transduction - drug effects; Histidine metabolism; Lipid metabolism; Histidine decarboxylase; Histamine H1 receptor; Macrophage
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1016/j.bbrc.2021.12.069

Distinct macrophage populations exert highly heterogeneity and perform various functions, among which, a crucial function of lipid metabolism is highlighted. However, the role of histidine metabolism disorder in macrophage lipid metabolism remains elusive. Addressed this question, we sorted and cultured the bone marrow-derived macrophages (BMDMs) of histidine decarboxylase (Hdc) knockout (Hdc−/-) mice with an in vitro oxidized low-density lipoprotein (ox-LDL) model, and detected the intracellular lipids by Oil Red O staining as well as lipid probe staining. Astemizole, a canonical and long-acting histamine H1 receptor (H1R) antagonist, was applied to elucidate the impact of antagonizing the H1R-dependent signaling pathway on macrophage lipid metabolism. Subsequently, the differential expressed genes were screened and analyzed in the bone marrow-derived CD11b+ immature myeloid cells of Hdc−/- and Hdc+/+ mice with a high fat diet by the microarray study. The expression levels of cholesterol metabolism-related genes were examined by qRT-PCR to explore underlying mechanisms. Lastly, we used a high-sensitivity histidine probe to detect the intracellular histidine in the BMDMs after oxidative stress. The results revealed that histidine metabolism disorder and histamine deficiency aggravated lipid accumulation in the ox-LDL-treated BMDMs. The expression level of H1R gene in the BMDMs was down-regulated after ox-LDL stimulation. The disruption of the H1R-dependent signaling pathway by astemizole further exacerbated ox-LDL-induced lipid deposition in the BMDMs partly by up-regulating scavenger receptor class A (SR-A) for lipid intake, down-regulating neutral cholesteryl ester hydrolase (nCEH) for cholesterol esterification and down-regulating ATP-binding cassette transporters A1 (ABCA1) and ABCG1 for reverse cholesterol transport. The intracellular histidine increased under ox-LDL condition, which was further increased by Hdc knockout. Collectively, these results partially reveal the relationship between histidine metabolism and lipid metabolism in the BMDMs and offer a novel strategy for lipid metabolism disorder-associated diseases. •There is a crosstalk between histidine metabolism and lipid metabolism in BMDMs.•Histamine deficiency aggravates lipid accumulation in the ox-LDL-treated BMDMs.•Disruption of H1R pathway exacerbates ox-LDL-induced lipid deposition in BMDMs.