scholarly journals The Lipolysome—A Highly Complex and Dynamic Protein Network Orchestrating Cytoplasmic Triacylglycerol Degradation

Metabolites ◽  
2020 ◽  
Vol 10 (4) ◽  
pp. 147
Author(s):  
Peter Hofer ◽  
Ulrike Taschler ◽  
Renate Schreiber ◽  
Petra Kotzbeck ◽  
Gabriele Schoiswohl
Keyword(s):  
Lipid Metabolism ◽  
Lysosomal Enzymes ◽  
Cellular Localization ◽  
Energy Homeostasis ◽  
Hormone Sensitive Lipase ◽  
Adipose Triglyceride Lipase ◽  
Monoacylglycerol Lipase ◽  
Sequential Action ◽  
Binding Partners ◽  
Hormone Sensitive

The catabolism of intracellular triacylglycerols (TAGs) involves the activity of cytoplasmic and lysosomal enzymes. Cytoplasmic TAG hydrolysis, commonly termed lipolysis, is catalyzed by the sequential action of three major hydrolases, namely adipose triglyceride lipase, hormone-sensitive lipase, and monoacylglycerol lipase. All three enzymes interact with numerous protein binding partners that modulate their activity, cellular localization, or stability. Deficiencies of these auxiliary proteins can lead to derangements in neutral lipid metabolism and energy homeostasis. In this review, we summarize the composition and the dynamics of the complex lipolytic machinery we like to call “lipolysome”.

Novel regulatory roles of carboxylesterase 3 in lipid metabolism and browning in 3T3-L1 white adipocytes

2019 ◽  
Vol 44 (10) ◽  
pp. 1089-1098 ◽  
Author(s):  
Sulagna Mukherjee ◽  
Minji Choi ◽  
Jong Won Yun
Keyword(s):  
Lipid Metabolism ◽  
Cell Model ◽  
Hormone Sensitive Lipase ◽  
Marker Genes ◽  
Acid Oxidation ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase ◽  
White Adipocytes ◽  
Enhanced Expression ◽  
Hormone Sensitive

The role of carboxylesterase 3 (Ces3) in the lipolysis of adipocytes has been overlooked, as 2 major lipolytic enzymes, hormone-sensitive lipase and adipose triglyceride lipase, play more powerful roles in lipolysis. In this study, we explored the effects of Ces3 in lipid metabolism by activating and inhibiting, as well as silencing, Ces3-encoding gene in 3T3-L1 cell model. Our results demonstrated that activation of Ces3 increased adipogenesis, and attenuated lipogenesis, whereas it promoted lipolysis and fatty acid oxidation. In addition, activated Ces3 led to enhanced expression of core fat browning marker genes and proteins, suggesting that Ces3 may play a pivotal role in fat browning and thermogenesis. In contrast, deficiency of Ces3 nullified the browning effect in white adipocytes, along with decreased adipogenesis in 3T3-L1 adipocytes. Interestingly, the expression pattern of adipose triglyceride lipase was in line with Ces3, whereas hormone-sensitive lipase was independently regulated irrespective of Ces3 expression levels, suggesting that Ces3 may play an important and compensatory role in the breakdown of triglycerides in white adipocytes. In conclusion, we provide the first evidence that activation of Ces3 contributes in the browning of white adipocytes, and maintains a balance in lipid metabolism, which could be a potential strategy in fighting against obesity.

scholarly journals Comparative studies of the role of hormone-sensitive lipase and adipose triglyceride lipase in human fat cell lipolysis

2007 ◽  
Vol 292 (6) ◽  
pp. E1847-E1855 ◽  
Author(s):  
Mikael Rydén ◽  
Johan Jocken ◽  
Vanessa van Harmelen ◽  
Andrea Dicker ◽  
Johan Hoffstedt ◽  
...  
Keyword(s):  
Protein Expression ◽  
Polycystic Ovary ◽  
Human Mesenchymal Stem Cells ◽  
Hormone Sensitive Lipase ◽  
Adipose Triglyceride Lipase ◽  
Human Adipocytes ◽  
Fat Cell ◽  
Triglyceride Lipase ◽  
Knock Down ◽  
Hormone Sensitive

Hormone-sensitive lipase (HSL) and adipose triglyceride lipase (ATGL) regulate adipocyte lipolysis in rodents. The purpose of this study was to compare the roles of these lipases for lipolysis in human adipocytes. Subcutaneous adipose tissue was investigated. HSL and ATGL protein expression were related to lipolysis in isolated mature fat cells. ATGL or HSL were knocked down by RNA interference (RNAi) or selectively inhibited, and effects on lipolysis were studied in differentiated preadipocytes or adipocytes derived from human mesenchymal stem cells (hMSC). Subjects were all women. There were 12 lean controls, 8 lean with polycystic ovary syndrome (PCOS), and 27 otherwise healthy obese subjects. We found that norepinephrine-induced lipolysis was positively correlated with HSL protein levels ( P < 0.0001) but not with ATGL protein. Women with PCOS or obesity had significantly decreased norepinephrine-induced lipolysis and HSL protein expression but no change in ATGL protein expression. HSL knock down by RNAi reduced basal and catecholamine-induced lipolysis. Knock down of ATGL decreased basal lipolysis but did not change catecholamine-stimulated lipolysis. Treatment of hMSC with a selective HSL inhibitor during and/or after differentiation in adipocytes reduced basal lipolysis by 50%, but stimulated lipolysis was inhibited completely. In contrast to findings in rodents, ATGL is of less importance than HSL in regulating catecholamine-induced lipolysis and cannot replace HSL when this enzyme is continuously inhibited. However, both lipases regulate basal lipolysis in human adipocytes. ATGL expression, unlike HSL, is not influenced by obesity or PCOS.

scholarly journals Adipocyte hormone-sensitive lipase: a major regulator of lipid metabolism

1996 ◽  
Vol 55 (1B) ◽  
pp. 93-109 ◽  
Author(s):  
Dominique Langin ◽  
Cecilia Holm ◽  
Max Lafontan
Keyword(s):  
Lipid Metabolism ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive ◽  
Lipase A

Regulation of lipid metabolism in adipose tissue during early starvation

1996 ◽  
Vol 271 (3) ◽  
pp. E541-E546 ◽  
Author(s):  
J. S. Samra ◽  
M. L. Clark ◽  
S. M. Humphreys ◽  
I. A. Macdonald ◽  
K. N. Frayn
Keyword(s):  
Adipose Tissue ◽  
Lipid Metabolism ◽  
Strong Relationship ◽  
Venous Drainage ◽  
Hormone Sensitive Lipase ◽  
Nonesterified Fatty Acid ◽  
Plasma Insulin Concentration ◽  
Relative Contribution ◽  
Hormone Sensitive ◽  
Subcutaneous Adipose

We studied changes in lipid metabolism in adipose tissue in 24 healthy adults during early starvation (14-20 h) by cannulating the venous drainage of the subcutaneous adipose tissue of the anterior abdominal wall. Net nonesterified fatty acid (NEFA) efflux from adipose tissue increased steadily from 1,790 +/- 300 to 2,360 +/- 290 nmol.100 g-1.min-1 (P = 0.03), due to increasing transcapillary efflux of NEFA (release from adipocytes; P < 0.01). The reesterification rate after an overnight fast was close to zero; thus, reduction in the rate of reesterification played no part in the increased transcapillary efflux of NEFA. One-quarter of the net efflux of NEFA after an overnight fast arose from the action of lipoprotein lipase (LPL), although this relative contribution decreased during the study (P < 0.02). The increased transcapillary efflux of NEFA reflected a significant increase in the rate of action of hormone-sensitive lipase (HSL; P = 0.03). There was a strong relationship between mean arterial NEFA concentration and net NEFA release from adipose tissue (P < 0.001), implying that the particular depot studied reflects the behavior of adipose tissue as a whole. Thus the increasing efflux of NEFA from adipose tissue observed during early starvation is due to an increased rate of action of HSL, which may in turn be regulated by a fall in the plasma insulin concentration.

Fasting upregulates adipose triglyceride lipase and hormone-sensitive lipase levels and phosphorylation in mouse kidney

2015 ◽  
Vol 93 (3) ◽  
pp. 262-267 ◽  
Author(s):  
Phillip M. Marvyn ◽  
Ryan M. Bradley ◽  
Emily B. Button ◽  
Emily B. Mardian ◽  
Robin E. Duncan
Keyword(s):  
Fatty Acids ◽  
Hormone Sensitive Lipase ◽  
Binding Motif ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase ◽  
Protein Levels ◽  
Fasted State ◽  
Esterified Fatty Acids ◽  
Glomerular Filtrate ◽  
Hormone Sensitive

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.

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