Molecular mechanisms regulating hormone-sensitive lipase and lipolysis

2003 ◽  
Vol 31 (6) ◽  
pp. 1120-1124 ◽  
Author(s):  
C. Holm
Keyword(s):  
Lipid Droplet ◽  
Molecular Mechanisms ◽  
Hormone Sensitive Lipase ◽  
Glucose Disposal ◽  
Triacylglycerol Lipase ◽  
Insulin Resistant ◽  
Lipolytic Action ◽  
Key Enzyme ◽  
Hormone Sensitive

HSL (hormone-sensitive lipase) is a key enzyme in the mobilization of fatty acids from acylglycerols in adipocytes as well as non-adipocytes. In adipocytes, catecholamines stimulate lipolysis mainly through PKA (protein kinase A)-mediated phosphorylation of HSL and perilipin, a protein coating the lipid droplet. The anti-lipolytic action of insulin is mediated mainly via lowered cAMP levels, accomplished through activation of phosphodiesterase 3B. Phosphorylation of HSL by PKA occurs at three sites, the serines 563, 659 and 660, both in vitro and in primary rat adipocytes. Phosphorylation of Ser-659 and -660 is required for in vitro activation as well as translocation from the cytosol to the lipid droplet, whereas the role of the third PKA site remains elusive. Adipocytes isolated from homozygous HSL-null mice, generated in our laboratory, exhibit completely blunted catecholamine-induced glycerol release and reduced fatty acid release, suggesting the presence of additional, although not necessarily hormone-activatable, triacylglycerol lipase(s). Basal hyperinsulinaemia, release of exaggerated amounts of insulin during glucose challenges and retarded glucose disposal during insulin tolerance tests suggest that HSL-null mice are insulin resistant. Liver, adipose tissue and skeletal muscle appear all to be sites of impaired insulin sensitivity in HSL-null mice.

In vitro SAR of (5-(2H)-isoxazolonyl) ureas, potent inhibitors of hormone-sensitive lipase

2004 ◽  
Vol 14 (12) ◽  
pp. 3155-3159 ◽  
Author(s):  
Derek B. Lowe ◽  
Steven Magnuson ◽  
Ning Qi ◽  
Ann-Marie Campbell ◽  
James Cook ◽  
...  
Keyword(s):  
Hormone Sensitive Lipase ◽  
Hormone Sensitive

scholarly journals Reactive Oxygen Species Facilitate Translocation of Hormone Sensitive Lipase to the Lipid Droplet During Lipolysis in Human Differentiated Adipocytes

PLoS ONE ◽  
2012 ◽  
Vol 7 (4) ◽  
pp. e34904 ◽  
Author(s):  
Sarah A. Krawczyk ◽  
Jorge F. Haller ◽  
Tom Ferrante ◽  
Raphael A. Zoeller ◽  
Barbara E. Corkey
Keyword(s):  
Reactive Oxygen Species ◽  
Lipid Droplet ◽  
Reactive Oxygen ◽  
Hormone Sensitive Lipase ◽  
Oxygen Species ◽  
Hormone Sensitive

scholarly journals PKC and ERK mediate GH-stimulated lipolysis

2013 ◽  
Vol 51 (2) ◽  
pp. 213-224 ◽  
Author(s):  
Heather E Bergan ◽  
Jeffrey D Kittilson ◽  
Mark A Sheridan
Keyword(s):  
Molecular Mechanisms ◽  
De Novo ◽  
Hormone Sensitive Lipase ◽  
Akt Pathway ◽  
Lipolytic Enzyme ◽  
Erk Pathway ◽  
Physiological Processes ◽  
Kinase C ◽  
Hormone Sensitive ◽  
Growth Promoting

GH regulates several physiological processes in vertebrates, including the promotion of growth, an anabolic process, and the mobilization of stored lipids, a catabolic process. In this study, we used hepatocytes isolated from rainbow trout (Oncorhynchus mykiss) as a model to examine the mechanism of GH action on lipolysis. GH stimulated lipolysis as measured by increased glycerol release in both a time- and a concentration-related manner. The promotion of lipolysis was accompanied by GH-stimulated phosphorylation of the lipolytic enzyme hormone-sensitive lipase (HSL). GH-stimulated lipolysis was also manifested by an increased expression of the two HSL-encoding mRNAs, HSL1 and HSL2. The signaling pathways that underlie GH-stimulated lipolysis were also studied. GH resulted in the activation of phospholipase C (PLC)/protein kinase C (PKC) and the MEK/ERK pathway, whereas JAK–STAT and the PI3K–Akt pathway were deactivated. The blockade of PLC/PKC and the MEK/ERK pathway inhibited GH-stimulated lipolysis and GH-stimulated phosphorylation of HSL as well as GH-stimulated HSL mRNA expression, whereas the blockade of JAK–STAT or the PI3K–Akt pathway had no effect on the activation of lipolysis or the expression of HSL stimulated by GH. These results indicate that GH promotes lipolysis by activating HSL and by enhancing the de novo expression of HSL mRNAs via the activation of PKC and ERK. These findings also suggest molecular mechanisms for activating the lipid catabolic actions of GH while simultaneously deactivating anabolic processes such as antilipolysis and the growth-promoting actions of GH.

Molecular mechanisms underlying regional variations of catecholamine-induced lipolysis in rat adipocytes

1995 ◽  
Vol 268 (6) ◽  
pp. E1135-E1142 ◽  
Author(s):  
G. Tavernier ◽  
J. Galitzky ◽  
P. Valet ◽  
A. Remaury ◽  
A. Bouloumie ◽  
...  
Keyword(s):  
Molecular Mechanisms ◽  
Subcutaneous Fat ◽  
Hormone Sensitive Lipase ◽  
Mrna Levels ◽  
Fat Depots ◽  
White Adipocytes ◽  
Adrenoceptor Agonists ◽  
Hormone Sensitive ◽  
Beta 2 ◽  
Fat Depot

The mechanisms underlying catecholamine control of lipolysis were studied in rat white adipocytes from epididymal, retroperitoneal, and subcutaneous fat depots. Sensitivity of subcutaneous adipocytes to selective beta 3-adrenoceptor agonists was lower than that of internal adipocytes. beta 3-Adrenoceptor mRNA levels were lower in subcutaneous adipocytes. A decreased beta 1/beta 2-adrenoceptor-mediated lipolysis was also observed in these adipocytes, and the number of beta 1/beta 2-adrenoceptors was lower than in the internal adipocytes. The number of alpha 2-adrenoceptors was higher in subcutaneous adipocytes without a marked difference in alpha 2-adrenoceptor-mediated antilipolysis between the depots. Subcutaneous adipocytes were also characterized by a lower maximal lipolytic response to drugs acting at different levels of the lipolytic cascade, suggesting differences at the postreceptor level. Lower hormone-sensitive lipase activity and mRNA levels in subcutaneous adipocytes were in agreement with the lipolysis data. These results suggest that the pattern of expression of the genes of the lipolytic pathway varies with the anatomic location of the fat depot.

Endurance training changes in lipolytic responsiveness of obese adipose tissue

1998 ◽  
Vol 275 (6) ◽  
pp. E951-E956 ◽  
Author(s):  
I. De Glisezinski ◽  
F. Crampes ◽  
I. Harant ◽  
M. Berlan ◽  
J. Hejnova ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Physical Training ◽  
The Body ◽  
Hormone Sensitive Lipase ◽  
Aerobic Exercise Training ◽  
Adrenoceptor Agonist ◽  
Before And After ◽  
Hormone Sensitive ◽  
Obese Subjects

The aim of this study was to investigate the effect of aerobic exercise training on the lipolytic response of adipose tissue in obese subjects. Thirteen men (body mass index = 36.9 ± 1.3 kg/m2) were submitted to aerobic physical training on a cycloergometer (30–45 min, 4 days a wk) for 3 mo. Adipocyte sensitivity to the action of catecholamines and insulin was studied in vitro before and after training. Training induced a decrease in the percentage of fat mass ( P < 0.05) without changing the body weight. Basal lipolysis and hormone-sensitive lipase activity were significantly decreased after training ( P < 0.05). The lipolytic effects of epinephrine, isoprenaline (β-adrenoceptor agonist), and dobutamine (β1-adrenoceptor agonist) were significantly increased ( P < 0.05) but not those of procaterol (β2-adrenoceptor agonist). The antilipolytic effects of α2-adrenoceptor and insulin were significantly decreased ( P < 0.05). Lipolysis stimulation by agents acting at the postreceptor level was unchanged after training. In conclusion, aerobic physical training in obese male subjects modifies adipose tissue lipolysis through an enhancement of β-adrenergic response and a concomitant blunting of adipocyte antilipolytic activity.

scholarly journals Acetylation of Cavin-1 Promotes Lipolysis in White Adipose Tissue

2017 ◽  
Vol 37 (16) ◽  
Author(s):  
Shui-Rong Zhou ◽  
Liang Guo ◽  
Xu Wang ◽  
Yang Liu ◽  
Wan-Qiu Peng ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Molecular Mechanisms ◽  
Hormone Sensitive Lipase ◽  
Dependent Manner ◽  
Nutritional Regulation ◽  
Fat Mobilization ◽  
Hormone Sensitive ◽  
Shed Light

ABSTRACT White adipose tissue (WAT) serves as a reversible energy storage depot in the form of lipids in response to nutritional status. Cavin-1, an essential component in the biogenesis of caveolae, is a positive regulator of lipolysis in adipocytes. However, molecular mechanisms of cavin-1 in the modulation of lipolysis remain poorly understood. Here, we showed that cavin-1 was acetylated at lysines 291, 293, and 298 (3K), which were under nutritional regulation in WAT. We further identified GCN5 as the acetyltransferase and Sirt1 as the deacetylase of cavin-1. Acetylation-mimetic 3Q mutants of cavin-1 augmented fat mobilization in 3T3-L1 adipocytes and zebrafish. Mechanistically, acetylated cavin-1 preferentially interacted with hormone-sensitive lipase and recruited it to the caveolae, thereby promoting lipolysis. Our findings shed light on the essential role of cavin-1 in regulating lipolysis in an acetylation-dependent manner in WAT.

Sex differences in hormone-sensitive lipase expression, activity, and phosphorylation in skeletal muscle at rest and during exercise

2006 ◽  
Vol 291 (5) ◽  
pp. E1106-E1114 ◽  
Author(s):  
Carsten Roepstorff ◽  
Morten Donsmark ◽  
Maja Thiele ◽  
Bodil Vistisen ◽  
Greg Stewart ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Protein Content ◽  
Specific Activity ◽  
Exercise Bout ◽  
Total Activity ◽  
Hormone Sensitive Lipase ◽  
Expression Activity ◽  
Hormone Sensitive ◽  
Specific Regulation

Women have been shown to use more intramuscular triacylglycerol (IMTG) during exercise than men. To investigate whether this could be due to sex-specific regulation of hormone-sensitive lipase (HSL) and to use sex comparison as a model to gain further insight into HSL regulation, nine women and eight men performed bicycle exercise (90 min, 60% V̇o2peak), and skeletal muscle HSL expression, phosphorylation, and activity were determined. Supporting previous findings, basal IMTG content ( P < 0.001) and net IMTG decrease during exercise ( P < 0.01) were higher in women than in men and correlated significantly ( r = 0.72, P = 0.001). Muscle HSL mRNA (80%, P = 0.11) and protein content (50%, P < 0.05) were higher in women than in men. HSL total activity increased during exercise (47%, P < 0.05) but did not differ between sexes. Accordingly, HSL specific activity (HSL activity per HSL protein content) increased during exercise (62%, P < 0.05) and was generally higher in men than in women (82%, P < 0.05). A similar pattern was observed for HSL Ser659 phosphorylation, suggesting a role in regulation of HSL activity. Likewise, plasma epinephrine increased during exercise ( P < 0.05) and was higher in men than in women during the end of the exercise bout ( P < 0.05). We conclude that, although HSL expression and Ser659 phosphorylation in skeletal muscle during exercise is sex specific, total muscle HSL activity measured in vitro was similar between sexes. The higher basal IMTG content in women compared with men is therefore the best candidate to explain the higher IMTG net hydrolysis during exercise in women.

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