Triglycerides are stored in intracellular lipid droplets in mammalian cells. Current evidences suggest that the intracellular lipid droplets are active participants in a variety of metabolic processes, and thus are considered as functional organelles in cells. The lipid droplet is composed of a triglyceride core surrounded by a phospholipid monolayer in which several proteins are embedded. Four of these proteins belong to a family of structurally related PAT protein, which includes perilipin, ADRP, TIP47 and S3-12. In this review, we summarize the functions of these proteins in the modulation of lipolysis and lipid droplets formation.
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EMBO J
January 2025
Cambridge Institute for Medical Research, University of Cambridge, Cambridge, CB2 0XY, UK.
Biogenesis of membrane-bound organelles involves the synthesis, remodeling, and degradation of their constituent phospholipids. How these pathways regulate organelle size remains poorly understood. Here we demonstrate that a lipid-degradation pathway inhibits expansion of the endoplasmic reticulum (ER) membrane.
View Article and Find Full Text PDFChemistry
January 2025
Shiv Nadar University, CHEMISTRY, NH 91, TEHSIL DADRI, GAUSTAM BUDHA NAGAR, 201314, GREATER NOIDA, INDIA.
Since death is an inevitable phenomenon, exploring cell deaths holds importance. During this process, the cellular microenvironment within cells such as pH, polarity, viscosity etc alter. One such microenvironment, viscosity elevates during different cell deaths.
View Article and Find Full Text PDFInflammation
January 2025
Department of Neurology, Nanjing Drum Tower Hospital, Affiliated Hospital of Medical School, Nanjing University, Nanjing, China.
Microglia-mediated neuroinflammation plays a crucial role in multiple neurological diseases. We have previously found that Atglistatin, the mouse Adipose Triglyceride Lipase (ATGL) inhibitor, could promote lipid droplets (LDs) accumulation and suppress LPS-induced neuroinflammation in mouse microglia. However, Atglistatin was species-selective, which limited its use in clinical settings.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Columbia University, New York, NY, USA.
Background: Lipid dysregulation is a known feature of Alzheimer's Disease. Importantly, alterations in lipids pathways affect immune responses in cells like microglia, which have been shown to accumulate cholesterol in both aging and neurodegeneration. Recently, the presence of TDP-43 inclusions has been linked to increased severity of cognitive impairment in AD patients.
View Article and Find Full Text PDFAlzheimers Dement
December 2024
Department of Neurology, Vanderbilt University Medical Center, Nashville, TN, USA.
Background: Microglial processing and recycling of debris is implicated in AD. AD GWAS loci are enriched for genes in efferocytosis, phagocytosis, endosomal trafficking and cholesterol efflux. Acting as a buffer, lipid droplets increase as a consequence of an imbalance between lipid debris influx and efflux rates.
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