scholarly journals Isolation of cDNAs for perilipins A and B: sequence and expression of lipid droplet-associated proteins of adipocytes.

1993 ◽  
Vol 90 (24) ◽  
pp. 12035-12039 ◽  
Author(s):  
A. S. Greenberg ◽  
J. J. Egan ◽  
S. A. Wek ◽  
M. C. Moos ◽  
C. Londos ◽  
...  
2018 ◽  
Vol 56 (01) ◽  
pp. E2-E89
Author(s):  
H Witzel ◽  
L Pawella ◽  
V Rausch ◽  
S Mueller ◽  
J Schattenberg ◽  
...  

2022 ◽  
Vol 8 ◽  
Author(s):  
Hai-bo Zhang ◽  
Wen Su ◽  
Hu Xu ◽  
Xiao-yan Zhang ◽  
You-fei Guan

Nonalcoholic fatty liver disease (NAFLD), especially in its inflammatory form (steatohepatitis, NASH), is closely related to the pathogenesis of chronic liver disease. Despite substantial advances in the management of NAFLD/NASH in recent years, there are currently no efficacious therapies for its treatment. The biogenesis and expansion of lipid droplets (LDs) are critical pathophysiological processes in the development of NAFLD/NASH. In the past decade, increasing evidence has demonstrated that lipid droplet-associated proteins may represent potential therapeutic targets for the treatment of NAFLD/NASH given the critical role they play in regulating the biogenesis and metabolism of lipid droplets. Recently, HSD17B13, a newly identified liver-enriched, hepatocyte-specific, lipid droplet-associated protein, has been reported to be strongly associated with the development and progression of NAFLD/NASH in both mice and humans. Notably, human genetic studies have repeatedly reported a robust association of HSD17B13 single nucleotide polymorphisms (SNPs) with the occurrence and severity of NAFLD/NASH and other chronic liver diseases (CLDs). Here we briefly overview the discovery, tissue distribution, and subcellular localization of HSD17B13 and highlight its important role in promoting the pathogenesis of NAFLD/NASH in both experimental animal models and patients. We also discuss the potential of HSD17B13 as a promising target for the development of novel therapeutic agents for NAFLD/NASH.


2009 ◽  
Vol 23 (S1) ◽  
Author(s):  
Dawn L Brasaemle ◽  
Gabriela Montero‐Moran ◽  
Derek McMahon ◽  
Jorge M Caviglia ◽  
Xiaofang Liang ◽  
...  

2005 ◽  
Vol 46 (5) ◽  
pp. 885-895 ◽  
Author(s):  
Soonkyu Chung ◽  
Jonathan Mark Brown ◽  
Maria Boysen Sandberg ◽  
Michael McIntosh

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Nen-Chung Chang ◽  
Aming Chor-Ming Lin ◽  
Cheng-Chen Hsu ◽  
Jung-Sheng Liu ◽  
Leo Tsui ◽  
...  

Lipid metabolism in visceral fat cells is correlated with metabolic syndrome and cardiovascular diseases. Okadaic-acid, a 38-carbon fatty acid isolated from the black spongeHalichondria okadai, can stimulate lipolysis by promoting the phosphorylation of several proteins in adipocytes. However, the mechanism of okadaic acid-induced lipolysis and the effects of okadaic acid on lipid-droplet-associated proteins (perilipins and beta-actin) remain unclear. We isolated adipocytes from rat epididymal fat pads and treated them with isoproterenol and/or okadaic acid to estimate lipolysis by measuring glycerol release. Incubating adipocytes with okadaic acid stimulated time-dependent lipolysis. Lipid-droplet-associated perilipins and beta-actin were analyzed by immunoblotting and immunofluorescence, and the association of perilipin A and B was found to be decreased in response to isoproterenol or okadaic acid treatment. Moreover, okadaic-acid treatment could enhance isoproterenol-mediated lipolysis, whereas treatment of several inhibitors such as KT-5720 (PKA inhibitor), calphostin C (PKC inhibitor), or KT-5823 (PKG inhibitor) did not attenuate okadaic-acid-induced lipolysis. By contrast, vanadyl acetylacetonate (tyrosine phosphatase inhibitor) blocked okadaic-acid-dependent lipolysis. These results suggest that okadaic acid induces the phosphorylation and detachment of lipid-droplet-associated perilipin A and B from the lipid droplet surface and thereby leads to accelerated lipolysis.


2020 ◽  
Author(s):  
Montserrat A. de la Rosa Rodriguez ◽  
Anne Gemmink ◽  
Michel van Weeghel ◽  
Marie Louise Aoun ◽  
Christina Warnecke ◽  
...  

ABSTRACTLipid droplets (LD) are dynamic organelles that can expand and shrink, driven by fluctuations in the rate of triglyceride synthesis and degradation. Triglyceride synthesis, storage in LD, and degradation are governed by a complex set of LD-associated proteins. One of these LD-associated proteins, hypoxia-inducible lipid droplet-associated (HILPDA), was found to impair LD breakdown by inhibiting adipose triglyceride lipase. Here we characterized the physiological role and mechanism of action of HILPDA in hepatocytes. Expression of HILPDA was induced by fatty acids in several hepatoma cell lines. Hepatocyte-specific deficiency of HILPDA in mice modestly but significantly reduced hepatic triglycerides in mice with non-alcoholic fatty liver disease. Similarly, deficiency of HILPDA in mouse precision-cut liver slices and primary hepatocytes reduced lipid storage and accumulation of fluorescently-labelled fatty acids in LD, respectively, which was independent of adipose triglyceride lipase. Fluorescence microscopy showed that HILPDA partly colocalizes with LD and with the endoplasmic reticulum, is especially abundant in perinuclear areas, and mainly associates with newly added fatty acids. Real-time fluorescence live-cell imaging further revealed that HILPDA preferentially localizes to LD that are being remodelled. Mechanistically, HILPDA overexpression increased lipid storage in human hepatoma cells concomitant with an increase in DGAT activity and DGAT1 protein levels. Finally, confocal microscopy and Förster resonance energy transfer-fluorescence lifetime imaging microscopy analysis indicated that HILPDA colocalizes and physically interacts with DGAT1. Overall, our data indicate that HILPDA physically interacts with DGAT1 and increases DGAT activity. These findings suggest a novel mechanism in hepatocytes that links elevated fatty acid levels to stimulation of triglyceride synthesis and storage.


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