Lipid Droplets in Health and Disease

Önal, Gizem; Kutlu, Özlem; Gözüaçık, Devrim; Emre, Serap

doi:10.1186/s12944-017-0521-7

Cited by 242 publications

(208 citation statements)

References 178 publications

(184 reference statements)

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“…32 LD accumulation is closely associated with human metabolic syndrome including atherosclerosis. 26,33 Thus, increased levels of LDs can signify either an increase in LD biogenesis or a disruption in the downstream degradation pathway (lipolysis and lipophagy). 34 In our study, oxLDL had no significant effect on LD biogenesis or lipolysis and we postulated that Autophagy is a highly conserved cellular homoeostatic 'housekeeping' process and it plays a critical role in the clearance of damaged organelles to maintain cell stability and metabolic homoeostasis.…”

Section: Discussionmentioning

confidence: 99%

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

Wang

Liu

et al. 2019

J Cellular Molecular Medi

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The formation of fat‐laden foam cells, which contributes to the fatty streaks in the plaques of atheromas, is an important process in atherosclerosis. Vascular smooth muscle cells (VSMCs) are a critical origin of foam cells. However, the mechanisms that underlie VSMC foam cell formation are not yet completely understood. Here, we demonstrated that oxidized low‐density lipoprotein (oxLDL) inhibited lipophagy by suppressing lipid droplet (LD)‐lysosome fusion and increased VSMC foam cell formation. Moreover, although oxLDL treatment inhibited lysosomal biogenesis, it had no significant effect on lysosomal proteolysis and lysosomal pH. Notably, through TMT‐based quantitative proteomic analysis and database searching, 94 differentially expressed proteins were identified, of which 54 were increased and 40 were decreased in the oxLDL group compared with those in the control group. Subsequently, SCD1, a protein of interest, was further investigated. SCD1 levels in the VSMCs were down‐regulated by exposure to oxLDL in a time‐dependent manner and the interaction between SCD1 and LDs was also disrupted by oxLDL. Importantly, SCD1 overexpression enhanced LD‐lysosome fusion, increased lysosomal biogenesis and inhibited VSMC foam cell formation by activating TFEB nuclear translocation and its reporter activity. Modulation of the SCD1/TFEB‐mediated lipophagy machinery may offer novel therapeutic approaches for the treatment of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

Wang

Liu

et al. 2019

J Cellular Molecular Medi

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“…This is in agreement with the accepted view that lipid droplets are dynamic organelles composed of a neutral lipid core and a surface phospholipid monolayer. 137 Lipid droplets were formerly recognised as deposit of lipid esters; they are now redefined as authentic organelles that are actively engaged in a myriad of functions. 136 On the other hand, lipid droplets engulfed by autophagosomes are frequent in the vicinity of clusters of droplets ( Figure 6C,D), reflecting the mechanism of their degradation.…”

Section: Lipid Drople Ts: a D Is Tin C T Fe Ature Of β -Tanyc Y Te mentioning

confidence: 99%

“…135 Each lipid droplet is partially surrounded by RER cisternae, and sometimes the droplet surface is continuous with the cytoplasmic leaflet of the endoplasmic reticulum membrane ( Figure 6C), agreeing with the view that lipid droplets arise from the budding of RER membranes. [135][136][137][138][139] They are composed of a hydrophobic lipid ester core surrounded by a phospholipid monolayer membrane studded with proteins. 137 Lipid droplets were formerly recognised as deposit of lipid esters; they are now redefined as authentic organelles that are actively engaged in a myriad of functions.…”

Section: Lipid Drople Ts: a D Is Tin C T Fe Ature Of β -Tanyc Y Te mentioning

confidence: 99%

“…136 On the other hand, lipid droplets engulfed by autophagosomes are frequent in the vicinity of clusters of droplets ( Figure 6C,D), reflecting the mechanism of their degradation. 137 Proteomics studies have revealed that over two hundred different proteins are localised to the surface of lipid droplets 137,140 including perilipin, a protein that specifically localises on the surface of lipid droplets. [135][136][137][138][139] They are composed of a hydrophobic lipid ester core surrounded by a phospholipid monolayer membrane studded with proteins.…”

Section: Lipid Drople Ts: a D Is Tin C T Fe Ature Of β -Tanyc Y Te mentioning

confidence: 99%

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Tanycytes: A rich morphological history to underpin future molecular and physiological investigations

Rodríguez

Guerra

Peruzzo

et al. 2019

J Neuroendocrinology

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Tanycytes are located at the base of the brain and retain characteristics from their developmental origins, such as radial glial cells, throughout their life span. With transport mechanisms and modulation of tight junction proteins, tanycytes form a bridge connecting the cerebrospinal fluid with the external limiting basement membrane. They also retain the powers of self‐renewal and can differentiate to generate neurones and glia. Similar to radial glia, they are a heterogeneous family with distinct phenotypes. Although the four subtypes so far distinguished display distinct characteristics, further research is likely to reveal new subtypes. In this review, we have re‐visited the work of the pioneers in the field, revealing forgotten work that is waiting to inspire new research with today's cutting‐edge technologies. We have conducted a systematic ultrastructural study of α‐tanycytes that resulted in a wealth of new information, generating numerous questions for future study. We also consider median eminence pituicytes, a closely‐related cell type to tanycytes, and attempt to relate pituicyte fine morphology to molecular and functional mechanism. Our rationale was that future research should be guided by a better understanding of the early pioneering work in the field, which may currently be overlooked when interpreting newer data or designing new investigations.

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“…LDs are dynamic organelles implicated in metabolic disorders including obesity and T2D, which are marked by abnormal LD accumulation. 4,5 Structurally, LDs are natural micelles composed of a hydrophobic core containing triglycerides, cholesterol esters and a corona made of phospholipids that can serve as lipid storage sites and as a platform for the recruitment of signalling molecules. 6,7 Perilipin associated proteins (PAT) coat and stabilize the surface of LD by reducing lipases access to the lipid core.…”

Section: Introductionmentioning

confidence: 99%

Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β‐cells

Petropavlovskaia

Khatchadourian

et al. 2019

J Cellular Molecular Medi

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Both type 2 diabetes (T2D) and obesity are characterized by excessive hyperlipidaemia and subsequent lipid droplet (LD) accumulation in adipose tissue. To investigate whether LDs also accumulate in β‐cells of T2D patients, we assessed the expression of PLIN2, a LD‐associated protein, in non‐diabetic (ND) and T2D pancreata. We observed an up‐regulation of PLIN2 mRNA and protein in β‐cells of T2D patients, along with significant changes in the expression of lipid metabolism, apoptosis and oxidative stress genes. The increased LD buildup in T2D β‐cells was accompanied by inhibition of nuclear translocation of TFEB, a master regulator of autophagy and by down‐regulation of lysosomal biomarker LAMP2. To investigate whether LD accumulation and autophagy were influenced by diabetic conditions, we used rat INS‐1 cells to model the effects of hyperglycaemia and hyperlipidaemia on autophagy and metabolic gene expression. Consistent with human tissue, both LD formation and PLIN2 expression were enhanced in INS‐1 cells under hyperglycaemia, whereas TFEB activation and autophagy gene expression were significantly reduced. Collectively, these results suggest that lipid clearance and overall homeostasis is markedly disrupted in β‐cells under hyperglycaemic conditions and interventions ameliorating lipid clearance could be beneficial in reducing functional impairments in islets caused by glucolipotoxicity.

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Lipid Droplets in Health and Disease

Cited by 242 publications

References 178 publications

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

SCD1 activation impedes foam cell formation by inducing lipophagy in oxLDL‐treated human vascular smooth muscle cells

Tanycytes: A rich morphological history to underpin future molecular and physiological investigations

Type 2 diabetes is associated with suppression of autophagy and lipid accumulation in β‐cells

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