Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment

Abstract

; BECN1: beclin 1, autophagy related; BW: body weight; CNS: central nervous system; Co-IP: co-immunoprecipitation; DACI: diabetes-associated cognitive impairment; DAPI: 4',6-diamidino-2-phenylindole; DGs: dentate gyrus; DLG4/PSD95: discs large MAGUK scaffold protein 4; DMEM: Dulbecco's modified Eagle's medium; DSST: digit symbol substitution test; EDTA: ethylenedinitrilotetraacetic acid; ELISA: enzyme linked immunosorbent assay; GFAP: glial fibrillary acidic protein; HFD: high-fat diet; HG: high glucose; IFNG/IFN-γ: interferon gamma; IL1B/IL-1β: interleukin 1 beta; IL4: interleukin 4; IL6: interleukin 6; IL10: interleukin 10; LDs: lipid droplets; LPS: lipopolysaccharide; MAP2: microtubule associated protein 2; MAP1LC3B/LC3B: microtubule associated protein 1 light chain 3 beta; MWM: morris water maze; NFKB/NF-κB: nuclear factor of kappa light polypeptide gene enhancer in B cells; NLRP3: NLR family pyrin domain containing 3; NOS2/iNOS: nitric oxide synthase 2, inducible; NOR: novel object recognition; OA: oleic acid; PA: palmitic acid; PBS: phosphate-buffered saline; PFA: paraformaldehyde; PLIN2: perilipin 2; PLIN3: perilipin 3; PS: penicillin-streptomycin solution; RAPA: rapamycin; RBFOX3/NeuN: RNA binding protein, fox-1 homolog (C. elegans) 3; RELA/p65: RELA proto-oncogene, NF-kB subunit; ROS: reactive oxygen species; RT: room temperature; RT-qPCR: Reverse transcription quantitative real-time polymerase chain reaction; STZ: streptozotocin; SQSTM1/p62: sequestosome 1; SYK: spleen asociated tyrosine kinase; SYP: synaptophysin; T2DM: type 2 diabetes mellitus; TNF/TNF-α: tumor necrosis factor; TREM1: triggering receptor expressed on myeloid cells 1; TUNEL: terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling.