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 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 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.

scholarly journals Evidence of a possible role for Lys-γ3-MSH in the regulation of adipocyte function

2007 ◽  
Vol 196 (1) ◽  
pp. 149-158 ◽  
Author(s):  
Stephen C Harmer ◽  
David J Pepper ◽  
Katy Cooke ◽  
Hugh P J Bennett ◽  
Andrew B Bicknell
Keyword(s):  
Physiological Role ◽  
Hormone Sensitive Lipase ◽  
Melanocortin Receptor ◽  
Rat Tissues ◽  
Binding Studies ◽  
Cortical Cells ◽  
Perilipin A ◽  
Hormone Sensitive ◽  
Adrenal Cortical Cells

Lys-γ3-MSH is a melanocortin peptide derived from the C-terminal of the 16 kDa fragment of POMC. The physiological role of Lys-γ3-MSH is unclear, although it has previously been shown that, although not directly steroidogenic, it can act to potentiate the steroidogenic response of adrenal cortical cells to ACTH. This synergistic effect appears to be correlated with an ability to increase the activity of hormone sensitive lipase (HSL) and therefore the rate of cholesterol ester hydrolysis. Ligand binding studies have suggested that high-affinity binding sites for Lys-γ3-MSH exist in the adrenal gland and a number of other rat tissues that express HSL, including adipose, skeletal muscle and testes. To investigate the hypothesis that Lys-γ3-MSH may play a wider role in cholesterol and lipid metabolism, we tested the effect of Lys-γ3-MSH on lipolysis, an HSL-mediated process, in 3T3-L1 adipocytes. In comparison with other melanocortin peptides, Lys-γ3-MSH was found to be a potent stimulator of lipolysis. It was also able to phosphorylate HSL at key serine residues and stimulate the hyperphosphorylation of perilipin A. The receptor through which the lipolytic actions of Lys-γ3-MSH are being mediated is not clear. Attempts to characterise this receptor suggest that either the pharmacology of the melanocortin receptor 5 in 3T3-L1 adipocytes is different from that described when expressed in heterologous systems or the possibility that a further, as yet uncharacterised, receptor exists.

scholarly journals Role of Hormone-sensitive Lipase in Leptin-Promoted Fat Loss and Glucose Lowering

2017 ◽  
Vol 24 (11) ◽  
pp. 1105-1116 ◽  
Author(s):  
Mikio Takanashi ◽  
Yoshino Taira ◽  
Sachiko Okazaki ◽  
Satoru Takase ◽  
Takeshi Kimura ◽  
...  
Keyword(s):  
Hormone Sensitive Lipase ◽  
Glucose Lowering ◽  
Fat Loss ◽  
Hormone Sensitive

Hormone-sensitive lipase knockout mice have increased hepatic insulin sensitivity and are protected from short-term diet-induced insulin resistance in skeletal muscle and heart

2005 ◽  
Vol 289 (1) ◽  
pp. E30-E39 ◽  
Author(s):  
So-Young Park ◽  
Hyo-Jeong Kim ◽  
Shupei Wang ◽  
Takamasa Higashimori ◽  
Jianying Dong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Glucose Metabolism ◽  
Insulin Action ◽  
Hormone Sensitive Lipase ◽  
Wild Type ◽  
High Fat ◽  
Hormone Sensitive ◽  
Fat Feeding

Insulin resistance in skeletal muscle and heart plays a major role in the development of type 2 diabetes and diabetic heart failure and may be causally associated with altered lipid metabolism. Hormone-sensitive lipase (HSL) is a rate-determining enzyme in the hydrolysis of triglyceride in adipocytes, and HSL-deficient mice have reduced circulating fatty acids and are resistant to diet-induced obesity. To determine the metabolic role of HSL, we examined the changes in tissue-specific insulin action and glucose metabolism in vivo during hyperinsulinemic euglycemic clamps after 3 wk of high-fat or normal chow diet in awake, HSL-deficient (HSL-KO) mice. On normal diet, HSL-KO mice showed a twofold increase in hepatic insulin action but a 40% decrease in insulin-stimulated cardiac glucose uptake compared with wild-type littermates. High-fat feeding caused a similar increase in whole body fat mass in both groups of mice. Insulin-stimulated glucose uptake was reduced by 50–80% in skeletal muscle and heart of wild-type mice after high-fat feeding. In contrast, HSL-KO mice were protected from diet-induced insulin resistance in skeletal muscle and heart, and these effects were associated with reduced intramuscular triglyceride and fatty acyl-CoA levels in the fat-fed HSL-KO mice. Overall, these findings demonstrate the important role of HSL on skeletal muscle, heart, and liver glucose metabolism.

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
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