Essential role of hormone-sensitive lipase (HSL) in the maintenance of lipid storage in Mycobacterium leprae-infected macrophages

2012 ◽  
Vol 52 (5) ◽  
pp. 285-291 ◽  
Author(s):  
Kazunari Tanigawa ◽  
Yang Degang ◽  
Akira Kawashima ◽  
Takeshi Akama ◽  
Aya Yoshihara ◽  
...  
Keyword(s):  
Essential Role ◽  
Mycobacterium Leprae ◽  
Lipid Storage ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive

Hormone-sensitive lipase activity and triacylglycerol hydrolysis are decreased in rat soleus muscle by cyclopiazonic acid

2003 ◽  
Vol 285 (2) ◽  
pp. E412-E419 ◽  
Author(s):  
Matthew J. Watt ◽  
Gregory R. Steinberg ◽  
G. J. F. Heigenhauser ◽  
Lawrence L. Spriet ◽  
David J. Dyck
Keyword(s):  
Soleus Muscle ◽  
Kinase Inhibitor ◽  
Energy State ◽  
Muscle Tension ◽  
Cyclopiazonic Acid ◽  
Lipid Storage ◽  
Hormone Sensitive Lipase ◽  
Cellular Energy ◽  
Triacylglycerol Hydrolysis ◽  
Hormone Sensitive

Cyclopiazonic acid (CPA) is a sarcoplasmic reticulum Ca2+-ATPase inhibitor that increases intracellular calcium. The role of CPA in regulating the oxidation and esterification of palmitate, the hydrolysis of intramuscular lipids, and the activation of hormone-sensitive lipase (HSL) was examined in isolated rat soleus muscles at rest. CPA (40 μM) was added to the incubation medium to levels that resulted in subcontraction increases in muscle tension, and lipid metabolism was monitored using the previously described pulse-chase procedure. CPA did not alter the cellular energy state, as reflected by similar muscle contents of ATP, phosphocreatine, free AMP, and free ADP. CPA increased total palmitate uptake into soleus muscle (11%, P < 0.05) and was without effect on palmitate oxidation. This resulted in greater esterification of exogenous palmitate into the triacylglycerol (18%, P < 0.05) and phospholipid (89%, P < 0.05) pools. CPA decreased ( P < 0.05) intramuscular lipid hydrolysis, and this occurred as a result of reduced HSL activity (20%, P < 0.05). Incubation of muscles with 3 mM caffeine, which is also known to increase Ca2+ without affecting the cellular energy state, reduced HSL activity (24%, P < 0.05). KN-93, a calcium/calmodulin-dependent kinase inhibitor (CaMKII), blocked the effects of CPA and caffeine, and HSL activity returned to preincubation values. The results of the present study demonstrate that CPA simultaneously decreases intramuscular triacylglycerol (IMTG) hydrolysis and promotes lipid storage in isolated, intact soleus muscle. The decreased IMTG hydrolysis is likely mediated by reduced HSL activity, possibly via the CaMKII pathway. These responses are not consistent with the increased hydrolysis and decreased esterification observed in contracting muscle when substrate availability and the hormonal milieu are tightly controlled. It is possible that more powerful signals or a higher [Ca2+] may override the lipid-storage effect of the CPA-mediated effects during muscular contractions.

scholarly journals AMPK Phosphorylates Desnutrin/ATGL and Hormone-Sensitive Lipase To Regulate Lipolysis and Fatty Acid Oxidation within Adipose Tissue

2016 ◽  
Vol 36 (14) ◽  
pp. 1961-1976 ◽  
Author(s):  
Sun-Joong Kim ◽  
Tianyi Tang ◽  
Marcia Abbott ◽  
Jose A. Viscarra ◽  
Yuhui Wang ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Protein Kinase ◽  
Hydrolase Activity ◽  
Hormone Sensitive Lipase ◽  
Acid Oxidation ◽  
Peroxisome Proliferator ◽  
Hormone Sensitive

The role of AMP-activated protein kinase (AMPK) in promoting fatty acid (FA) oxidation in various tissues, such as liver and muscle, has been well understood. However, the role of AMPK in lipolysis and FA metabolism in adipose tissue has been controversial. To investigate the role of AMPK in the regulation of adipose lipolysisin vivo, we generated mice with adipose-tissue-specific knockout of both the α1 and α2 catalytic subunits of AMPK (AMPK-ASKO mice) by using aP2-Cre and adiponectin-Cre. Both models of AMPK-ASKO ablation show no changes in desnutrin/ATGL levels but have defective phosphorylation of desnutrin/ATGL at S406 to decrease its triacylglycerol (TAG) hydrolase activity, lowering basal lipolysis in adipose tissue. These mice also show defective phosphorylation of hormone-sensitive lipase (HSL) at S565, with higher phosphorylation at protein kinase A sites S563 and S660, increasing its hydrolase activity and isoproterenol-stimulated lipolysis. With higher overall adipose lipolysis, both models of AMPK-ASKO mice are lean, having smaller adipocytes with lower TAG and higher intracellular free-FA levels. Moreover, FAs from higher lipolysis activate peroxisome proliferator-activated receptor delta to induce FA oxidative genes and increase FA oxidation and energy expenditure. Overall, for the first time, we providein vivoevidence of the role of AMPK in the phosphorylation and regulation of desnutrin/ATGL and HSL and thus adipose lipolysis.

scholarly journals Ovarian Cycle-Specific Regulation of Adipose Tissue Lipid Storage by Testosterone in Female Nonhuman Primates

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4126-4135 ◽  
Author(s):  
Oleg Varlamov ◽  
Michael P. Chu ◽  
Whitney K. McGee ◽  
Judy L. Cameron ◽  
Robert W. O'Rourke ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Fatty Acid ◽  
Sex Hormones ◽  
Luteal Phase ◽  
Fatty Acid Uptake ◽  
Ovarian Cycle ◽  
Lipid Storage ◽  
Hormone Sensitive Lipase ◽  
Acid Uptake ◽  
Hormone Sensitive

Previous studies in rodents and humans suggest that hyperandrogenemia causes white adipose tissue (WAT) dysfunction in females, although the underlying mechanisms are poorly understood. In light of the differences in the length of the ovarian cycle between humans and rodents, we used a nonhuman primate model to elucidate the effects of chronic hyperandrogenemia on WAT function in vivo. Female rhesus macaques implanted with testosterone capsules developed insulin resistance and altered leptin secretion on a high-fat, Western-style diet. In control visceral WAT, lipolysis and hormone-sensitive lipase expression were upregulated during the luteal phase compared with the early follicular (menses) phase of the ovarian cycle. Hyperandrogenemia attenuated elevated lipolysis and hormone-sensitive lipase activity in visceral WAT during the luteal phase but not during menses. Under control conditions, insulin-stimulated Akt and Erk activation and fatty acid uptake in WAT were not significantly affected by the ovarian cycle. In contrast, testosterone treatment preferentially increased fatty acid uptake and insulin signaling at menses. The fatty acid synthase and glucose transporter-4 genes were upregulated by testosterone during the luteal phase. In summary, this study reveals ovarian stage-specific fluctuations in adipocyte lipolysis and suggests that male sex hormones increase and female sex hormones decrease lipid storage in female WAT.

Investigation into the role of the hormone sensitive lipase −60C>G promoter variant in morbid obesity

2005 ◽  
Vol 15 (1) ◽  
pp. 31-35 ◽  
Author(s):  
Philippa J. Talmud ◽  
Jutta Palmen ◽  
Anna M. Wolf ◽  
Ulrike Beisiegel
Keyword(s):  
Morbid Obesity ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive

scholarly journals Defective Lysosomal Lipolysis Causes Prenatal Lipid Accumulation and Exacerbates Immediately after Birth

2021 ◽  
Vol 22 (19) ◽  
pp. 10416
Author(s):  
Katharina B. Kuentzel ◽  
Ivan Bradić ◽  
Alena Akhmetshina ◽  
Melanie Korbelius ◽  
Silvia Rainer ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Clinical Manifestations ◽  
Premature Death ◽  
Cholesterol Homeostasis ◽  
Hormone Sensitive Lipase ◽  
Infantile Form ◽  
Fetal Organ ◽  
Hormone Sensitive ◽  
Lipid Storage Disorder

Cholesterol and fatty acids are essential lipids that are critical for membrane biosynthesis and fetal organ development. Cholesteryl esters (CE) are degraded by hormone-sensitive lipase (HSL) in the cytosol and by lysosomal acid lipase (LAL) in the lysosome. Impaired LAL or HSL activity causes rare pathologies in humans, with HSL deficiency presenting less severe clinical manifestations. The infantile form of LAL deficiency, a lysosomal lipid storage disorder, leads to premature death. However, the importance of defective lysosomal CE degradation and its consequences during early life are incompletely understood. We therefore investigated how defective CE catabolism affects fetus and infant maturation using Lal and Hsl knockout (-/-) mouse models. This study demonstrates that defective lysosomal but not neutral lipolysis alters placental and fetal cholesterol homeostasis and exhibits an initial disease pathology already in utero as Lal-/- fetuses accumulate hepatic lysosomal lipids. Immediately after birth, LAL deficiency exacerbates with massive hepatic lysosomal lipid accumulation, which continues to worsen into young adulthood. Our data highlight the crucial role of LAL during early development, with the first weeks after birth being critical for aggravating LAL deficiency.

The atrial natriuretic peptide- and catecholamine-induced lipolysis and expression of related genes in adipose tissue in hypothyroid and hyperthyroid patients

2007 ◽  
Vol 293 (1) ◽  
pp. E246-E251 ◽  
Author(s):  
J. Polak ◽  
C. Moro ◽  
E. Klimcakova ◽  
M. Kovacikova ◽  
M. Bajzova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Adipose Tissue ◽  
Atrial Natriuretic Peptide ◽  
Thyroid Hormones ◽  
Natriuretic Peptide ◽  
Hormone Sensitive Lipase ◽  
Hormone Sensitive ◽  
Hyperthyroid Patients ◽  
Atrial Natriuretic

Thyroid dysfunction is associated with several abnormalities in intermediary metabolism, including impairment of lipolytic response to catecholamines in subcutaneous abdominal adipose tissue (SCAAT). Atrial natriuretic peptide (ANP) is a powerful lipolytic peptide; however, the role of ANP-mediated lipolysis in thyroid disease has not been elucidated. The aim of this study was to investigate the role of thyroid hormones in the regulation of ANP-induced lipolysis as well as in the gene expression of hormone-sensitive lipase, phosphodiesterase 3B (PDE3B), uncoupling protein-2 (UCP2), natriuretic peptide receptor type A, and β2-adrenergic receptor in SCAAT of hyperthyroid and hypothyroid patients. Gene expression in SCAAT was studied in 13 hypothyroid and 11 hyperthyroid age-matched women before and 2–4 mo after the normalization of their thyroid status. A microdialysis study was performed on a subset of nine hyperthyroid and 10 hypothyroid subjects. ANP- and isoprenaline-induced lipolyses were higher in hyperthyroid subjects, with no differences between the groups following treatment. Hormone-sensitive lipase gene expression was higher in hyperthyroid compared with hypothyroid subjects before treatment, whereas no difference was observed following treatment. No differences in gene expression of other genes were observed between the two groups. Following treatment, the gene expression of UCP2 decreased in hyperthyroid, whereas the expression of PDE3B decreased in hypothyroid subjects. We conclude that thyroid hormones regulate ANP- and isoprenaline-mediated lipolysis in human SCAAT in vivo. Increased lipolytic subcutaneous adipose tissue response in hyperthyroid patients may involve postreceptor signaling mechanisms.

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