scholarly journals Adipose triglyceride lipase in immune response, inflammation, and atherosclerosis

2012 ◽  
Vol 393 (9) ◽  
pp. 1005-1011 ◽  
Author(s):  
Branislav Radovic ◽  
Elma Aflaki ◽  
Dagmar Kratky

Abstract Consistent with its central importance in lipid and energy homeostasis, lipolysis occurs in essentially all tissues and cell types, including macrophages. The hydrolytic cleavage of triacylglycerol by adipose triglyceride lipase (ATGL) generates non-esterified fatty acids, which are subsequently used as essential precursors for lipid and membrane synthesis, mediators in cell signaling processes or as energy substrate in mitochondria. This review summarizes the current knowledge concerning the consequences of ATGL deficiency in macrophages with particular emphasis on macrophage (dys)-function, apoptosis, and atherosclerosis.

Lipids ◽  
2011 ◽  
Vol 46 (9) ◽  
pp. 813-820 ◽  
Author(s):  
Julie Serr ◽  
Yeunsu Suh ◽  
Shin-Ae Oh ◽  
Sangsu Shin ◽  
Minseok Kim ◽  
...  

2015 ◽  
Vol 93 (3) ◽  
pp. 262-267 ◽  
Author(s):  
Phillip M. Marvyn ◽  
Ryan M. Bradley ◽  
Emily B. Button ◽  
Emily B. Mardian ◽  
Robin E. Duncan

Circulating non-esterified fatty acids (NEFA) rise during fasting and are taken up by the kidneys, either directly from the plasma or during re-uptake of albumin from glomerular filtrate, and are stored as triacylglycerol (TAG). Subsequent utilization of stored fatty acids requires their hydrolytic release from cellular lipid droplets, but relatively little is known about renal lipolysis. We found that total [3H]triolein hydrolase activity of kidney lysates was significantly increased by 15% in the fasted state. Adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) mRNA expression was time-dependently increased by fasting, along with other fatty acid metabolism genes (Pparα, Cd36, and Aox). ATGL and HSL protein levels were also significantly induced (by 239 ± 7% and 322 ± 8%, respectively). Concomitant with changes in total protein levels, there was an increase in ATGL phosphorylation at the AMPK-regulated serine 406 site in the 14-3-3 binding motif, and an increase in HSL phosphorylation at serines 565 and 660 that are regulated by AMPK and PKA, respectively. Using immunofluorescence, we further demonstrate nearly ubiquitous expression of ATGL in the renal cortex with a concentration on the apical/lumenal surface of some cortical tubules. Our findings suggest a role for ATGL and HSL in kidney 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.


Endocrinology ◽  
2012 ◽  
Vol 153 (5) ◽  
pp. 2198-2207 ◽  
Author(s):  
Jiang Wei Wu ◽  
Shu Pei Wang ◽  
Stéphanie Casavant ◽  
Alain Moreau ◽  
Gong She Yang ◽  
...  

2019 ◽  
Vol 317 (5) ◽  
pp. F1398-F1403 ◽  
Author(s):  
Elena Isaeva ◽  
Mykhailo Fedoriuk ◽  
Ruslan Bohovyk ◽  
Christine A. Klemens ◽  
Sherif Khedr ◽  
...  

Our current knowledge of the properties of renal ion channels responsible for electrolytes and cell energy homeostasis mainly relies on rodent studies. However, it has not been established yet to what extent their characteristics can be generalized to those of humans. The present study was designed to develop a standardized protocol for the isolation of well-preserved glomeruli and renal tubules from rodent and human kidneys and to assess the functional suitability of the obtained materials for physiological studies. Separation of nephron segments from human and rodent kidneys was achieved using a novel vibrodissociation technique. The integrity of isolated renal tubules and glomeruli was probed via electrophysiological analysis and fluorescence microscopy, and the purity of the collected fractions was confirmed using quantitative RT-PCR with gene markers for specific cell types. The developed approach allows rapid isolation of well-preserved renal tubules and glomeruli from human and rodent kidneys amenable for electrophysiological, Ca2+ imaging, and omics studies. Analysis of the basic electrophysiological parameters of major K+ and Na+ channels expressed in human cortical collecting ducts revealed that they exhibited similar biophysical properties as previously reported in rodent studies. Using vibrodissociation for nephron segment isolation has several advantages over existing techniques: it is less labor intensive, requires little to no enzymatic treatment, and produces large quantities of well-preserved experimental material in pure fractions. Applying this method for the separation of nephron segments from human and rodent kidneys may be a powerful tool for the indepth assessment of kidney function in health and disease.


2010 ◽  
Vol 299 (2) ◽  
pp. E162-E168 ◽  
Author(s):  
Matthew J. Watt ◽  
Lawrence L. Spriet

Fatty acids derived from the hydrolysis of adipose tissue and skeletal muscle triacylglycerol (TG) are an important energy substrate at rest and during physical activity. This review outlines the identification of the new TG lipase, adipose triglyceride lipase, the current understanding of how cellular TG lipases are regulated, and the implications for understanding the integrated control of TG lipolysis. Furthermore, this review outlines recent advances that propose a “revised” role for TG lipases in cellular function, metabolic homeostasis, and disease prevention.


2009 ◽  
Vol 51 (3) ◽  
pp. 490-499 ◽  
Author(s):  
Gabriele Schoiswohl ◽  
Martina Schweiger ◽  
Renate Schreiber ◽  
Gregor Gorkiewicz ◽  
Karina Preiss-Landl ◽  
...  

2015 ◽  
Vol 308 (10) ◽  
pp. E879-E890 ◽  
Author(s):  
John J. Dubé ◽  
Mitch T. Sitnick ◽  
Gabriele Schoiswohl ◽  
Rachel C. Wills ◽  
Mahesh K. Basantani ◽  
...  

Adipose triglyceride lipase (ATGL) is the rate-limiting enzyme mediating triacylglycerol hydrolysis in virtually all cells, including adipocytes and skeletal myocytes, and hence, plays a critical role in mobilizing fatty acids. Global ATGL deficiency promotes skeletal myopathy and exercise intolerance in mice and humans, and yet the tissue-specific contributions to these phenotypes remain unknown. The goal of this study was to determine the relative contribution of ATGL-mediated triacylglycerol hydrolysis in adipocytes vs. skeletal myocytes to acute exercise performance. To achieve this goal, we generated murine models with adipocyte- and skeletal myocyte-specific targeted deletion of ATGL. We then subjected untrained mice to acute peak and submaximal exercise interventions and assessed exercise performance and energy substrate metabolism. Impaired ATGL-mediated lipolysis within adipocytes reduced peak and submaximal exercise performance, reduced peripheral energy substrate availability, shifted energy substrate preference toward carbohydrate oxidation, and decreased HSL Ser660 phosphorylation and mitochondrial respiration within skeletal muscle. In contrast, impaired ATGL-mediated lipolysis within skeletal myocytes was not sufficient to reduce peak and submaximal exercise performance or peripheral energy substrate availability and instead tended to enhance metabolic flexibility during peak exercise. Furthermore, the expanded intramyocellular triacylglycerol pool in these mice was reduced following exercise in association with preserved HSL phosphorylation, suggesting that HSL may compensate for impaired ATGL action in skeletal muscle during exercise. These data suggest that adipocyte rather than skeletal myocyte ATGL-mediated lipolysis plays a greater role during acute exercise in part because of compensatory mechanisms that maintain lipolysis in muscle, but not adipose tissue, when ATGL is absent.


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