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.

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 Adipose triglyceride lipase in immune response, inflammation, and atherosclerosis

2012 ◽  
Vol 393 (9) ◽  
pp. 1005-1011 ◽  
Author(s):  
Branislav Radovic ◽  
Elma Aflaki ◽  
Dagmar Kratky
Keyword(s):  
Fatty Acids ◽  
Energy Homeostasis ◽  
Current Knowledge ◽  
Cell Types ◽  
Adipose Triglyceride Lipase ◽  
Hydrolytic Cleavage ◽  
Central Importance ◽  
Energy Substrate ◽  
Triglyceride Lipase ◽  
Esterified Fatty Acids

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.

Acute Up-Regulation of Adipose Triglyceride Lipase and Release of Non-Esterified Fatty Acids by Dexamethasone in Chicken Adipose Tissue

Lipids ◽  
2011 ◽  
Vol 46 (9) ◽  
pp. 813-820 ◽  
Author(s):  
Julie Serr ◽  
Yeunsu Suh ◽  
Shin-Ae Oh ◽  
Sangsu Shin ◽  
Minseok Kim ◽  
...  
Keyword(s):  
Fatty Acids ◽  
Adipose Tissue ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase ◽  
Esterified Fatty Acids

scholarly journals Fasting, But Not Exercise, Increases Adipose Triglyceride Lipase (ATGL) Protein and Reduces G(0)/G(1) Switch Gene 2 (G0S2) Protein and mRNA Content in Human Adipose Tissue

2011 ◽  
Vol 96 (8) ◽  
pp. E1293-E1297 ◽  
Author(s):  
Thomas S. Nielsen ◽  
Mikkel H. Vendelbo ◽  
Niels Jessen ◽  
Steen B. Pedersen ◽  
Jens O. Jørgensen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Research Unit ◽  
Hormone Sensitive Lipase ◽  
University Hospital ◽  
Adipose Triglyceride Lipase ◽  
Triglyceride Lipase ◽  
Protein Levels ◽  
Mrna Content ◽  
Underlying Mechanisms

Abstract Context: Fasting and exercise are characterized by increased lipolysis, but the underlying mechanisms are not fully understood. Objective: The study was designed to test whether fasting and exercise affect mRNA and protein levels of adipose triglyceride lipase (ATGL) and G(0)/G(1) switch gene 2 (G0S2), a recently discovered ATGL inhibitor, in humans. Design and Participants: We studied eight healthy men (age, 25.5 ± 4.3 yr) for 6 h (a 4-h basal and a 2-h clamp period) on three occasions in a randomized crossover design: 1) in the basal state and after; 2) 72-h fasting; and 3) 1-h exercise (65% VO2max). Subcutaneous abdominal adipose tissue (AT) biopsies were taken at t = 30 and 270 min. Setting: The study was conducted at a university hospital research unit. Results: Circulating free fatty acids and GH were increased, and C-peptide was decreased by both fasting and exercise. During fasting, insulin failed to suppress free fatty acid levels, suggesting AT insulin resistance. ATGL protein was increased 44% (P &lt; 0.001), and G0S2 mRNA and protein were decreased 56% (P = 0.02) and 54% (P = 0.01), respectively, after fasting, but both ATGL and G0S2 were unaffected by exercise. Protein levels of hormone-sensitive lipase and comparative gene identification-58 were unaffected throughout. Conclusions: We found increased AT content of ATGL and decreased protein and mRNA content of the ATGL inhibitor G0S2, suggesting increased ATGL activity during fasting, but not after short-term exercise. These findings are compatible with the notion that the ATGL-G0S2 complex is an important long-term regulator of lipolysis under physiological conditions such as fasting in humans.

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