Microscopy tools for the investigation of intracellular lipid storage and dynamics

Daemen, Sabine; Zandvoort, Marc A. M. J. van; Parekh, Sapun H.; Hesselink, Matthijs K. C.

doi:10.1016/j.molmet.2015.12.005

Cited by 90 publications

(103 citation statements)

References 77 publications

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“…1a). For detailed quantitative analysis we co-localized TMEM119 + microglia with BODIPY, a dye that specifically labels neutral lipids and is commonly used to detect lipid droplets 36,37 . We observed that in the aged brain, BODIPY + microglia were abundant in the hippocampus but scarce in other regions ( Supplementary Fig.…”

Section: Microglia Accumulate Lipid Droplets In the Aging Brainmentioning

confidence: 99%

Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain

Marschallinger

Iram

Zardeneta

et al. 2019

Preprint

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Microglia become progressively activated and seemingly dysfunctional with age, and genetic studies have linked these cells to the pathogenesis of a growing number of neurodegenerative diseases. Here we report a striking buildup of lipid droplets in microglia with aging in mouse and human brains. These cells, which we call lipid droplet-accumulating microglia (LAM), are defective in phagocytosis, produce high levels of reactive oxygen species, and secrete proinflammatory cytokines. RNA sequencing analysis of LAM revealed a transcriptional profile driven by innate inflammation distinct from previously reported microglial states. An unbiased CRISPR-Cas9 screen identified genetic modifiers of lipid droplet formation; surprisingly, variants of several of these genes, including progranulin, are causes of autosomal dominant forms of human neurodegenerative diseases. We thus propose that LAM contribute to agerelated and genetic forms of neurodegeneration.

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Section: Microglia Accumulate Lipid Droplets In the Aging Brainmentioning

confidence: 99%

Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain

Marschallinger

Iram

Zardeneta

et al. 2019

Preprint

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“…coherent anti-stokes Raman scattering, and imaging mass spectrometry, e.g. secondary ion mass spectrometry, could enable the role of specific lipid species in their subcellular localization to be studied in the near future (Daemen et al, 2016).…”

Section: Location Of Lipidsmentioning

confidence: 99%

The effect of diet and exercise on lipid droplet dynamics in human muscle tissue

Daemen

Polanen

Hesselink

2018

Journal of Experimental Biology

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The majority of fat in the human body is stored as triacylglycerols in white adipose tissue. In the obese state, adipose tissue mass expands and excess lipids are stored in non-adipose tissues, such as skeletal muscle. Lipids are stored in skeletal muscle in the form of small lipid droplets. Although originally viewed as dull organelles that simply store lipids as a consequence of lipid overflow from adipose tissue, lipid droplets are now recognized as key components in the cell that exert a variety of relevant functions in multiple tissues (including muscle). Here, we review the effect of diet and exercise interventions on myocellular lipid droplets and their putative role in insulin sensitivity from a human perspective. We also provide an overview of lipid droplet biology and identify gaps for future research.

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“…We first focused on lipid-rich tissues such as sebaceous glands, myelin sheath in the brain, and adipose tissues, which showed strong CDL signals and weak CDP signal ( Figure 4F-I and Supplementary Figure 4A). Because the visualization of in situ lipid synthesis dynamics in mouse models had been particularly challenging with previous methods, which mostly capture the static level 37 , here we demonstrate the utility of DO-SRS in studying the development and metabolic homeostasis of the lipid-rich tissues. From those studies, we also gained new insights into mammalian lipogenesis.…”

Section: Visualizing De Novo Lipogenesis and Metabolic Homeostasis Inmentioning

confidence: 87%

Optical Imaging of Metabolic Dynamics in Animals

Shi

Zheng

Shen

et al. 2018

Preprint

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Direct visualization of metabolic dynamics in living tissues with high spatial and temporal resolution is essential to understanding many biological processes. Here we introduce a platform that combines deuterium oxide (D2O) probing with stimulated Raman scattering microscopy (DO-SRS) to image in situ metabolic activities. Enzymatic incorporation of D2O-derived deuterium into macromolecules generates carbondeuterium (C-D) bonds, which track biosynthesis in tissues and can be imaged by SRS in situ. Within the broad vibrational spectra of C-D bonds, we discovered lipid-, protein-, and DNA-specific Raman shifts and developed spectral unmixing methods to obtain C-D signals with macromolecular selectivity. DO-SRS enabled us to probe de novo lipogenesis in animals, image protein biosynthesis without tissue bias, and simultaneously visualize lipid and protein metabolism and reveal their different dynamics. DO-SRS, being noninvasive, universally applicable, and cost-effective, can be adapted to a broad range of biological systems to study development, tissue homeostasis, aging, and tumor heterogeneity. Results SRS imaging enables D2O to be a contrast agent for metabolic activitiesWater (H2O), the ubiquitous solvent of life, diffuses freely across cell and organelle membranes and participates in the vast majority of biochemical reactions. As an isotopologue of water, heavy water (D2O) can rapidly equilibrate with total body water in all cells within an organism and label cellular biomolecules with deuterium (D) by forming a variety of X-D bonds through non-enzymatic H/D exchange and enzymatic incorporation ( Figure 1A). The former is spontaneous and reversibly forms oxygen-deuterium (O-D), nitrogen-deuterium (N-D), and sulfur-deuterium (S-D) bonds on existing molecules, whereas the latter depends on enzyme-catalyzed chemical transformation that irreversibly breaks the O-D bond and forms C-D bonds on newly synthesized molecules 5 . Through such transformation, deuterium quickly labels the metabolic precursors, such as non-essential amino acids (NEAAs), acetyl-CoA, and deoxyribose, which are then slowly incorporated into proteins, lipids, and DNA,

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Microscopy tools for the investigation of intracellular lipid storage and dynamics

Cited by 90 publications

References 77 publications

Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain

Lipid droplet accumulating microglia represent a dysfunctional and pro-inflammatory state in the aging brain

The effect of diet and exercise on lipid droplet dynamics in human muscle tissue

Optical Imaging of Metabolic Dynamics in Animals

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