Lipid droplet proteins and metabolic diseases

Xu, Shimeng; Zhang, Xuelin; Liu, Pingsheng

doi:10.1016/j.bbadis.2017.07.019

Cited by 143 publications

(114 citation statements)

References 407 publications

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“…Another suggested mechanism involved in maintaining LD homoeostasis is altered lipolysis. Several genes involved in lipolysis, including ATGL , CGI‐58 , HSL , LAL and MGL , were tested . However, oxLDL treatment had no significant effect on the genes associated with lipolysis (Figure B).…”

Section: Resultsmentioning

confidence: 99%

“…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%

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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: Resultsmentioning

confidence: 99%

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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“…Even though no specific LD targeting signal has been found yet, LD-associated proteins that directly target to LDs usually contain a hydrophobic domain or amphipathic a-helix(17, 18). For instance, LD resident protein in plants, oleosin, is proposed to comprise an N-terminal amphipathic domain, a central hydrophobic domain, and a C-terminal amphipathic a-helical domain.…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, it is crucial to study the proteins associated with LDs to unveil the role of LD in biological processes as well as human metabolic diseases. To date, over 100 proteins have been found on LDs and some of them have been proved to be associated with human diseases(17, 18). However, thus far, there has been no report on identification of LD-associated proteins derived from noncoding transcripts.…”

Section: Introductionmentioning

confidence: 99%

Identification of Functional Noncoding RNA-encoded Proteins on Lipid Droplets

Huang

Bamigbade

et al. 2020

Preprint

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Over the past decade, great progress in sequencing technologies and computational biology has revealed that the majority of the mammalian genome considered to be noncoding is rich in functional elements able to produce proteins. Many RNA molecules, mis-annotated as noncoding, actually harbor small open reading frames that are predicted to code for proteins. Some of those proteins have been verified to play critical roles in multiple biological processes. The lipid droplet (LD) is a unique cellular organelle, conserved from bacteria to humans, and is closely associated with cellular lipid metabolism and metabolic disorders. No noncoding RNA-coded proteins have been identified on LDs. Here, for the first time, we searched the organelle for their presence. After the enrichment of small proteins of LDs isolated from myoblasts, we used mass spectrometry coupled with our lab made protein database to identify LD-associated noncoding RNA-encoded proteins (LDANPs). A total of 15 new proteins were identified. One of them was studied further and termed LDANP1. LDANP1 was localized on LDs by imaging, cell fractionation, and immunogold labeling. Like LD resident proteins, LDANP1 was degraded by the proteasome. Using the CRISPR/Cas9-mediated genome editing technique, the endogenous expression of LDANP1 was validated. The stable expression of LDANP1 suppressed the accumulation of triacylglycerol in oleic acid treated myoblasts and inhibited the rescue of palmitate-inhibited insulin sensitivity by oleic acid. In summary, we report for the first time that translatable, nominally noncoding RNA-derived proteins, which are new and cannot be identified using current research methods, were associated with LDs and that among these, LDANP1 modulated lipid metabolism and insulin sensitivity. The discovery of noncoding RNA-encoded proteins on LDs paves a new way for the research of LDs and lipid metabolism.

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“…Except triacylglycerol (TAG), neutral lipids in LDs also include cholesterol ester, retinyl ester, wax ester, and polyhydroxyalkanoate (PHA)/polyhydroxybutyrate (PHB). Therefore, abnormal LD dynamics as well as ectopic lipid storage have been directly linked to many metabolic syndromes, such as obesity, fatty liver, and atherosclerosis, and diabetes [34][35][36]. We and others have previously reported that several strains of bacteria contain LDs and identified their main functions [37][38][39][40].…”

mentioning

confidence: 99%

Identification of Lipid Droplets in Gut Microbiota

Zhang

Zhou

et al. 2020

Preprint

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Recent research has accumulating evidence to support that gut microbiota can be a newly discovered organ/tissue for humans. Although the functions of gut microbiota have been linked to almost all aspects of human physiological, most findings so far are still either belonged to correlational research or at preliminary stage of causal study due to the complexity of gut microbiota as well as lack of proper tools and methods. Thus, development of new approaches is essential and necessary. Lipid droplet is a cellular organelle governing cell lipid homeostasis that is directly related to human metabolic syndromes. Previously we and other groups found lipid droplets in several bacterial strains. We wonder if gut bacteria have lipid droplets. If so, these bacteria may play key roles to regulate gut lipid content, remove unnecessary lipids and produce useful lipid molecules for host. Here we identified lipid droplet-like structures in freshly isolated bacteria from mouse small and large intestines, as well as mouse and human feces. We also purified and analyzed lipid droplets from a cloned human gut bacterium Streptomyces thermovulgaris. Together, we demonstrate the existence of lipid droplets in gut microbiota and established an approach to study them. Results and Discussion LD-like structures in intestinal bacteriaRecent studies of gut microbiota have developed extremely fast and their composition and products have been associated with human physical and mental health [1][2][3][4][5][6][7][8][9][10][11][12][13][14][15][16][17][18]. Several sophistic approaches have been established to study gut microbiota, including high-throughput 16S rRNA sequencing, metagenomics, and massive bacterial cloning [19][20][21][22][23][24][25][26][27]. Since the number and species of gut microbiota are too huge, the resulting complexity is an obscure that makes their functions remain

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Lipid droplet proteins and metabolic diseases

Cited by 143 publications

References 407 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

Identification of Functional Noncoding RNA-encoded Proteins on Lipid Droplets

Identification of Lipid Droplets in Gut Microbiota

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