ArticleAutophagy2023
Impaired lipophagy induced-microglial lipid droplets accumulation contributes to the buildup of TREM1 in diabetes-associated cognitive impairment.
Article in Autophagy, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 124 papers, 1 of them a synthesis that pooled it.
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Who cites it
124 citing papers in PubMed, 1 synthesis or guideline pooled it, 183 citations in OpenAlex.
- Unveiling the relationship of the comorbidity between depression and type 2 diabetes mellitus: a macro analysis and micro interpretation.Frontiers in medicine · 2026Pooled it
- Design, synthesis and biological evaluation of donepezil-safinamide hybrids as dual AChE and MAO-B inhibitor for Alzheimer's disease treatment.Journal of enzyme inhibition and medicinal chemistry · 2026Article
- Lipophagy: A key regulator in oxidative stress and metabolic disorders.Genes & diseases · 2026Review
- Hippocampal AdipoR1 regulates the microglial response and delays disease progression in a mouse model of Alzheimer's disease.Molecular psychiatry · 2026Article
- Research Advances on Organelle-Targeted Drug Delivery Systems for the Treatment of Brain Tumors and Central Nervous System Inflammation.Pharmaceutics · 2026Review
- Fat on Fire: Disrupted Microglial Lipid Metabolism as a Driver of Anesthetic Neurotoxicity.Neuroscience bulletin · 2026Review
- The nuclear receptor ESRRA is a crucial regulator of acute kidney injury through inhibition of the lipophagy-ferroptosis axis.Autophagy · 2026Article
- Association of the TREM-1-STAT3 Axis With Stroke Severity and Functional Outcomes in Ischemic Stroke: A Prospective Case-Control Study.Brain and behavior · 2026Observational
- Isoorientin inhibits oxidative stress to ameliorate cognitive dysfunction in type 2 diabetes mice via GSK3β/Nrf2 axis.Metabolic brain disease · 2026Article
- Lactate alleviates early brain damage after subarachnoid hemorrhage: Regulation of lipid metabolism.Neural regeneration research · 2026Article
- Astrocytic SCAP deletion ameliorates diabetes-associated cognitive impairment by suppressing microglial neuroinflammation and lipid droplet accumulation via the LCN2-24p3R-mTOR axis.Cell death & disease · 2026Article
- Microglial IRF7-induced lipophagy impairment aggravates lipid droplet overload and impedes neurological recovery after ischemic stroke.Journal of neuroinflammation · 2026Article
- Lipophagy in disease: signaling control, organelle communication, and therapeutic opportunities.Cell communication and signaling : CCS · 2026Review
- From lipid overload to autophagy collapse: how lipid dysregulation drives chronic inflammation and metabolic disease.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- Effects of Dietary Protein Levels on Growth, Serum Physiology, Protein and Lipid Metabolism, and Antioxidant Responses in Black Carp (Metabolites · 2026Article
- The mechanisms and strategies for Alzheimer's disease prevention: An update.Acta pharmaceutica Sinica. B · 2026Review
- TREM1-mediated macrophage activation drives voriconazole-induced hepatic steatosis: Diagnostic and therapeutic implications.Journal of pharmaceutical analysis · 2026Article
- Article
- TRIM25 Suppresses Hippocampal Neuronal Autophagy under High Glucose via Ubiquitination and Degradation of SIX2.Journal of molecular neuroscience : MN · 2026Article
- MiR-144 Regulates Cognitive Dysfunction via NLRP3 Inflammasome and FoxO1/AdipoR Pathway in T2DM Mice.Molecular neurobiology · 2026Article
64 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation caused by microglial activation and consequent neurological impairment are prominent features of diabetes-associated cognitive impairment (DACI). Microglial lipophagy, a significant fraction of autophagy contributing to lipid homeostasis and inflammation, had mostly been ignored in DACI. Microglial lipid droplets (LDs) accumulation is a characteristic of aging, however, little is known about the pathological role of microglial lipophagy and LDs in DACI. Therefore, we hypothesized that microglial lipophagy could be an Achilles's heel exploitable to develop effective strategies for DACI therapy. Here, starting with characterization of microglial accumulation of LDs in leptin receptor-deficient (db/db) mice and in high-fat diet and STZ (HFD/STZ) induced T2DM mice, as well as in high-glucose (HG)-treated mice BV2, human HMC3 and primary mice microglia, we revealed that HG-dampened lipophagy was responsible for LDs accumulation in microglia. Mechanistically, accumulated LDs colocalized with the microglial specific inflammatory amplifier TREM1 (triggering receptor expressed on myeloid cells 1), resulting in the buildup of microglial TREM1, which in turn aggravates HG-induced lipophagy damage and subsequently promoted HG-induced neuroinflammatory cascades via NLRP3 (NLR family pyrin domain containing 3) inflammasome. Moreover, pharmacological blockade of TREM1 with LP17 in db/db mice and HFD/STZ mice inhibited accumulation of LDs and TREM1, reduced hippocampal neuronal inflammatory damage, and consequently improved cognitive functions. Taken together, these findings uncover a previously unappreciated mechanism of impaired lipophagy-induced TREM1 accumulation in microglia and neuroinflammation in DACI, suggesting its translational potential as an attractive therapeutic target for delaying diabetes-associated cognitive decline.
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