The Experts below are selected from a list of 3915 Experts worldwide ranked by ideXlab platform

Cecilia Holm - One of the best experts on this subject based on the ideXlab platform.

  • contraction induced lipolysis is not impaired by inhibition of Hormone Sensitive Lipase in skeletal muscle
    The Journal of Physiology, 2013
    Co-Authors: Thomas J Alsted, Cecilia Holm, Robert Zimmermann, Thorkil Ploug, Clara Prats, Annette K Serup, Louise D Hoeg, Peter Schjerling, Christian Fledelius, Henrik Galbo
    Abstract:

    In skeletal muscle Hormone-Sensitive Lipase (HSL) has long been accepted to be the principal enzyme responsible for lipolysis of intramyocellular triacylglycerol (IMTG) during contractions. However, this notion is based on in vitro Lipase activity data, which may not reflect the in vivo lipolytic activity. We investigated lipolysis of IMTG in soleus muscles electrically stimulated to contract ex vivo during acute pharmacological inhibition of HSL in rat muscles and in muscles from HSL knockout (HSL-KO) mice. Measurements of IMTG are complicated by the presence of adipocytes located between the muscle fibres. To circumvent the problem with this contamination we analysed intramyocellular lipid droplet content histochemically. At maximal inhibition of HSL in rat muscles, contraction-induced breakdown of IMTG was identical to that seen in control muscles (P < 0.001). In response to contractions IMTG staining decreased significantly in both HSL-KO and WT muscles (P < 0.05). In vitro TG hydrolase activity data revealed that adipose triglyceride Lipase (ATGL) and HSL collectively account for ∼98% of the TG hydrolase activity in mouse skeletal muscle, other TG Lipases accordingly being of negligible importance for lipolysis of IMTG. The present study is the first to demonstrate that contraction-induced lipolysis of IMTG occurs in the absence of HSL activity in rat and mouse skeletal muscle. Furthermore, the results suggest that ATGL is activated and plays a major role in lipolysis of IMTG during muscle contractions.

  • rye bran alkylresorcinols suppress adipocyte lipolysis and Hormone Sensitive Lipase activity
    Molecular Nutrition & Food Research, 2011
    Co-Authors: Ulrika Andersson, Cecilia Holm, Eva Degerman
    Abstract:

    The effects of alkylresorcinols (ARs) isolated from rye bran on adipocyte lipolysis, Hormone-Sensitive Lipase activity and phosphorylation and on phosphorylation of protein kinase A substrates were studied. Preincubation with ARs for 18 h suppressed catecholamine-stimulated lipolysis in 3T3-L1 adipocytes. Furthermore, phosphorylation of Hormone-Sensitive Lipase (HSL), a key Lipase responsible for stimulated lipolysis, and phosphorylation of protein kinase A substrates, were diminished after preincubation with ARs, whereas HSL protein expression was unaltered. ARs were also shown to inhibit HSL activity in an in vitro assay.

  • Hormone Sensitive Lipase hsl is also a retinyl ester hydrolase evidence from mice lacking hsl
    The FASEB Journal, 2009
    Co-Authors: Kristoffer Strom, Stephanie Lucas, Rune Blomhoff, Thomas E Gundersen, Ola Hansson, Celine Fernandez, Cecilia Holm
    Abstract:

    Here, we investigated the importance of Hormone-Sensitive Lipase (HSL) as a retinyl ester hydrolase (REH). REH activity was measured in vitro using recombinant HSL and retinyl palmitate. The expression of retinoic acid (RA)-regulated genes and retinoid metabolites were measured in high-fat diet fed HSL-null mice using real-time quantitative PCR and triple-stage liquid chromatography/tandem mass spectrometry, respectively. Age- and gender-matched wild-type littermates were used as controls. The REH activity of rat HSL was found to be higher than that against the hitherto best known HSL substrate, i.e., diacylglycerols. REH activity in white adipose tissue (WAT) of HSL-null mice was completely blunted and accompanied by increased levels of retinyl esters and decreased levels of retinol, retinaldehyde and all-trans RA. Accordingly, genes known to be positively regulated by RA were down-regulated in HSL-null mice, including pRb and RIP140, key factors promoting differentiation into the white over the brown adipocyte lineage. Dietary RA supplementation partly restored WAT mass and the expression of RA-regulated genes in WAT of HSL-null mice. These findings demonstrate the importance of HSL as an REH of adipose tissue and suggest that HSL via this action provides RA and other retinoids for signaling events that are crucial for adipocyte differentiation and lineage commitment.

  • attainment of brown adipocyte features in white adipocytes of Hormone Sensitive Lipase null mice
    PLOS ONE, 2008
    Co-Authors: Kristoffer Strom, Stephanie Lucas, Ola Hansson, Celine Fernandez, Pernilla Nevsten, Cecilia Klint, Sofia Moverareskrtic, F Sundler, Claes Ohlsson, Cecilia Holm
    Abstract:

    BACKGROUND: Hormone-Sensitive Lipase (HSL) is expressed predominantly in adipose tissue, where it plays an important role in catecholamine-stimulated hydrolysis of stored tri- and diglycerides, thus mobilizing fatty acids. HSL exhibits broad substrate specificity and besides acylglycerides it hydrolyzes cholesteryl esters, retinyl esters and lipoidal esters. Despite its role in fatty acid mobilization, HSL null mice have been shown to be resistant to diet-induced obesity. METHODOLOGY/PRINCIPAL FINDINGS: Following a high-fat diet (HFD) regimen, energy expenditure, measured using indirect calorimetry, was increased in HSL null mice. White adipose tissue of HSL null mice was characterized by reduced mass and reduced protein expression of PPARgamma, a key transcription factor in adipogenesis, and stearoyl-CoA desaturase 1, the expression of which is known to be positively correlated to the differentiation state of the adipocyte. The protein expression of uncoupling protein-1 (UCP-1), the highly specific marker of brown adipocytes, was increased 7-fold in white adipose tissue of HSL null mice compared to wildtype littermates. Transmission electron microscopy revealed an increase in the size of mitochondria of white adipocytes of HSL null mice. The mRNA expression of pRb and RIP140 was decreased in isolated white adipocytes, while the expression of UCP-1 and CPT1 was increased in HSL null mice compared to wildtype littermates. Basal oxygen consumption was increased almost 3-fold in white adipose tissue of HSL null mice and was accompanied by increased uncoupling activity. CONCLUSIONS: These data suggest that HSL is involved in the determination of white versus brown adipocytes during adipocyte differentiation The exact mechanism(s) underlying this novel role of HSL remains to be elucidated, but it seems clear that HSL is required to sustain normal expression levels of pRb and RIP140, which both promote differentiation into the white, rather than the brown, adipocyte lineage.

  • Adipose triglyceride Lipase and Hormone-Sensitive Lipase protein expression is decreased in the obese insulin-resistant state.
    Journal of Clinical Endocrinology and Metabolism, 2007
    Co-Authors: Johan Jocken, Dominique Langin, Peter Arner, Cecilia Holm, Egbert Smit, Wim Saris, Carine Valle, Gabby Hul, Ellen E. Blaak
    Abstract:

    AIM/HYPOTHESIS: Obesity is associated with increased triacylglycerol (TAG) storage in adipose tissue and insulin resistance. The mobilization of stored TAG is mediated by Hormone-Sensitive Lipase (HSL) and the recently discovered adipose triglyceride Lipase (ATGL). The aim of the present study was to examine whether ATGL and HSL mRNA and protein expression are altered in insulin-resistant conditions. In addition, we investigated whether a possible impaired expression could be reversed by a period of weight reduction. METHODS: Adipose tissue biopsies were taken from obese subjects (n = 44) with a wide range of insulin resistance, before and just after a 10-wk hypocaloric diet. ATGL and HSL protein and mRNA expression was determined by Western blot and quantitative RT-PCR, respectively. RESULTS: Fasting insulin levels and the degree of insulin resistance (using the homeostasis model assessment index for insulin resistance) were negatively correlated with ATGL and HSL protein expression, independent of age, gender, fat cell size, and body composition. Both mRNA and protein levels of ATGL and HSL were reduced in insulin-resistant compared with insulin-Sensitive subjects (P < 0.05). Weight reduction significantly decreased ATGL and HSL mRNA and protein expression. A positive correlation between the decrease in leptin and the decrease in ATGL protein level after weight reduction was observed. Finally, ATGL and HSL mRNA and protein levels seem to be highly correlated, indicating a tight coregulation and transcriptional control. CONCLUSIONS: In obese subjects, insulin resistance and hyperinsulinemia are strongly associated with ATGL and HSL mRNA and protein expression, independent of fat mass. Data on weight reduction indicated that also other factors (e.g. leptin) relate to ATGL and HSL protein expression.

Fredric B Kraemer - One of the best experts on this subject based on the ideXlab platform.

  • adipose triglyceride Lipase not Hormone Sensitive Lipase is the primary lipolytic enzyme in fasting elephant seals mirounga angustirostris
    Physiological and Biochemical Zoology, 2015
    Co-Authors: Melinda A Fowler, Daniel P. Costa, Wen Jun Shen, Daniel E Crocker, Fredric B Kraemer
    Abstract:

    AbstractLittle is known about the mechanisms that allow capital breeders to rapidly mobilize large amounts of body reserves. Northern elephant seals (Mirounga angustirostris) utilize fat reserves for maternal metabolism and to create high fat milk for the pup. Hormone-Sensitive Lipase (HSL) has been hypothesized to be an important lipolytic enzyme in fasting seals, but the activity of HSL and adipose triglyceride Lipase (ATGL) has not been quantified in fasting adult seals, nor has their relationship to milk lipid content been assessed. Blubber and milk samples were obtained from 18 early lactation and 19 late lactation females, as well as blubber from five early and five late molting female seals. Blubber lipolytic activity was assessed with radiometric assays. HSL activity was negligible in seal blubber at all fasting stages. Total triglyceride Lipase activity was stable among early and late lactation and early molt but increased in late molting seals. Relative abundance of ATGL protein increased across...

  • Hormone Sensitive Lipase modulates adipose metabolism through pparγ
    Biochimica et Biophysica Acta, 2011
    Co-Authors: Wen Jun Shen, Shailja Patel, Fredric B Kraemer, Dyron Jue, Lifen Liu
    Abstract:

    Hormone-Sensitive Lipase (HSL) is rate limiting for diacylglycerol and cholesteryl ester hydrolysis in adipose tissue and essential for complete Hormone-stimulated lipolysis. Gene expression profiling in HSL-/- mice suggests that HSL is important for modulating adipogenesis and adipose metabolism. To test whether HSL is required for the supply of intrinsic ligands for PPARγ for normal adipose differentiation, HSL-/- and wild-type (WT) littermates were fed normal chow (NC) and high-fat (HF) diets supplemented with or without rosiglitazone (200 mg/kg) for 16 weeks. Results show that supplementing rosiglitazone to an NC diet completely normalized the decreased body weight and adipose depots in HSL-/- mice. Additionally, rosiglitazone resulted in similar serum glucose, total cholesterol, FFA, and adiponectin values in WT and HSL-/- mice. Furthermore, rosiglitazone normalized the expression of genes involved in adipocyte differentiation, markers of adipocyte differentiation, and enzymes involved in triacylglycerol synthesis and metabolism, and cholesteryl ester homeostasis, in HSL-/- mice. Supplementing rosiglitazone to an HF diet resulted in improved glucose tolerance in both WT and HSL-/- animals and also partial normalization in HSL-/- mice of abnormal WAT gene expression, serum chemistries, organ and body weight changes. In vitro studies showed that adipocytes from WT animals can provide ligands for activation of PPARγ and that activation is further boosted following lipolytic stimulation, whereas adipocytes from HSL-/- mice displayed attenuated activation of PPARγ, with no change following lipolytic stimulation. These results suggest that one of the mechanisms by which HSL modulates adipose metabolism is by providing intrinsic ligands or pro-ligands for PPARγ.

  • functional interaction of Hormone Sensitive Lipase and perilipin in lipolysis
    Journal of Lipid Research, 2009
    Co-Authors: Wen Jun Shen, Andrew S Greenberg, Shailja Patel, Fredric B Kraemer, Hideaki Miyoshi
    Abstract:

    Adipocyte lipolysis is controlled by complex interactions of Lipases, cofactors, and structural proteins associated with lipid droplets. Perilipin (Plin) A is a major droplet-associated protein that functions as a scaffold, both suppressing basal and facilitating cAMP-dependent protein kinase (PKA)-stimulated lipolysis. Plin is required for the translocation of Hormone-Sensitive Lipase (HSL) from the cytosol to lipid droplets upon stimulation. In these studies, we provide direct evidence for a physical interaction of HSL with Plin. By coexpressing HSL with truncation mutations of Plin, we demonstrate using coimmunoprecipitation that HSL can interact with an N-terminal region located between amino acids 141 and 200 of Plin A as well as with a C-terminal region located between amino acids 406 and 480. The N-terminal construct, Plin 1-200, which does not associate with lipid droplets but interacts with HSL, can function as a dominant negative for PKA-stimulated lipolysis. Using confocal microscopy of Plin truncations, we demonstrate that sequences between amino acids 463 and 517 may be important for or participate in lipid targeting. The results suggest the translocation of HSL to the lipid droplet occurs by virtue of Plin localization to the surface of lipid droplets and a physical interaction of HSL occurring with sequences within the N-terminal region of Plin.

  • perilipin promotes Hormone Sensitive Lipase mediated adipocyte lipolysis via phosphorylation dependent and independent mechanisms
    Journal of Biological Chemistry, 2006
    Co-Authors: Hideaki Miyoshi, Sandra C Souza, Fredric B Kraemer, Julia Kovsan, Assaf Rudich, Hui Hong Zhang, Katherine J Strissel, Marcelo A Christoffolete, Antonio C Bianco, Martin S Obin
    Abstract:

    Abstract Hormone-Sensitive Lipase (HSL) is the predominant Lipase effector of catecholamine-stimulated lipolysis in adipocytes. HSL-dependent lipolysis in response to catecholamines is mediated by protein kinase A (PKA)-dependent phosphorylation of perilipin A (Peri A), an essential lipid droplet (LD)-associated protein. It is believed that perilipin phosphorylation is essential for the translocation of HSL from the cytosol to the LD, a key event in stimulated lipolysis. Using adipocytes retrovirally engineered from murine embryonic fibroblasts of perilipin null mice (Peri–/– MEF), we demonstrate by cell fractionation and confocal microscopy that up to 50% of cellular HSL is LD-associated in the basal state and that PKA-stimulated HSL translocation is fully supported by adenoviral expression of a mutant perilipin lacking all six PKA sites (Peri AΔ1–6). PKA-stimulated HSL translocation was confirmed in differentiated brown adipocytes from perilipin null mice expressing an adipose-specific Peri AΔ1–6 transgene. Thus, PKA-induced HSL translocation was independent of perilipin phosphorylation. However, Peri AΔ1–6 failed to enhance PKA-stimulated lipolysis in either MEF adipocytes or differentiated brown adipocytes. Thus, the lipolytic action(s) of HSL at the LD surface requires PKA-dependent perilipin phosphorylation. In Peri–/– MEF adipocytes, PKA activation significantly enhanced the amount of HSL that could be cross-linked to and co-immunoprecipitated with ectopic Peri A. Notably, this enhanced cross-linking was blunted in Peri–/– MEF adipocytes expressing Peri AΔ1–6. This suggests that PKA-dependent perilipin phosphorylation facilitates (either direct or indirect) perilipin interaction with LD-associated HSL. These results redefine and expand our understanding of how perilipin regulates HSL-mediated lipolysis in adipocytes.

  • physical association between the adipocyte fatty acid binding protein and Hormone Sensitive Lipase a fluorescence resonance energy transfer analysis
    Journal of Biological Chemistry, 2004
    Co-Authors: Anne J Smith, Fredric B Kraemer, Constantine Londos, Mark A Sanders, Brian R Thompson, David A. Bernlohr
    Abstract:

    Abstract Previous in vitro studies have established that Hormone Sensitive Lipase (HSL) and adipocyte fatty acid-binding protein (AFABP) form a physical complex that presumably positions the FABP to accept a product fatty acid generated during catalysis. To assess AFABP-HSL interaction within a cellular context, we have used lipocytes derived from 293 cells (C8PA cells) and examined physical association using fluorescence resonance energy transfer. Transfection of C8PA cells with cyan fluorescent protein (CFP)-HSL, yellow fluorescent protein (YFP)-adipocyte FABP, or YFP-liver FABP revealed that under basal conditions each protein was cytoplasmic. In the presence of 20 μm forskolin, CFP-HSL translocated to the triacylglycerol droplet, coincident with BODIPY-FA labeled depots. Fluorescence resonance energy transfer analysis demonstrated that CFP-HSL associated with YFP-adipocyte FABP in both basal and forskolin-treated cells. In contrast, little if any fluorescence resonance energy transfer could be detected between CFP-HSL and YFP-liver FABP. These results suggest that a pre-lipolysis complex containing at least AFABP and HSL exists and that the complex translocates to the surface of the lipid droplet.

Wen Jun Shen - One of the best experts on this subject based on the ideXlab platform.

  • adipose triglyceride Lipase not Hormone Sensitive Lipase is the primary lipolytic enzyme in fasting elephant seals mirounga angustirostris
    Physiological and Biochemical Zoology, 2015
    Co-Authors: Melinda A Fowler, Daniel P. Costa, Wen Jun Shen, Daniel E Crocker, Fredric B Kraemer
    Abstract:

    AbstractLittle is known about the mechanisms that allow capital breeders to rapidly mobilize large amounts of body reserves. Northern elephant seals (Mirounga angustirostris) utilize fat reserves for maternal metabolism and to create high fat milk for the pup. Hormone-Sensitive Lipase (HSL) has been hypothesized to be an important lipolytic enzyme in fasting seals, but the activity of HSL and adipose triglyceride Lipase (ATGL) has not been quantified in fasting adult seals, nor has their relationship to milk lipid content been assessed. Blubber and milk samples were obtained from 18 early lactation and 19 late lactation females, as well as blubber from five early and five late molting female seals. Blubber lipolytic activity was assessed with radiometric assays. HSL activity was negligible in seal blubber at all fasting stages. Total triglyceride Lipase activity was stable among early and late lactation and early molt but increased in late molting seals. Relative abundance of ATGL protein increased across...

  • Hormone Sensitive Lipase modulates adipose metabolism through pparγ
    Biochimica et Biophysica Acta, 2011
    Co-Authors: Wen Jun Shen, Shailja Patel, Fredric B Kraemer, Dyron Jue, Lifen Liu
    Abstract:

    Hormone-Sensitive Lipase (HSL) is rate limiting for diacylglycerol and cholesteryl ester hydrolysis in adipose tissue and essential for complete Hormone-stimulated lipolysis. Gene expression profiling in HSL-/- mice suggests that HSL is important for modulating adipogenesis and adipose metabolism. To test whether HSL is required for the supply of intrinsic ligands for PPARγ for normal adipose differentiation, HSL-/- and wild-type (WT) littermates were fed normal chow (NC) and high-fat (HF) diets supplemented with or without rosiglitazone (200 mg/kg) for 16 weeks. Results show that supplementing rosiglitazone to an NC diet completely normalized the decreased body weight and adipose depots in HSL-/- mice. Additionally, rosiglitazone resulted in similar serum glucose, total cholesterol, FFA, and adiponectin values in WT and HSL-/- mice. Furthermore, rosiglitazone normalized the expression of genes involved in adipocyte differentiation, markers of adipocyte differentiation, and enzymes involved in triacylglycerol synthesis and metabolism, and cholesteryl ester homeostasis, in HSL-/- mice. Supplementing rosiglitazone to an HF diet resulted in improved glucose tolerance in both WT and HSL-/- animals and also partial normalization in HSL-/- mice of abnormal WAT gene expression, serum chemistries, organ and body weight changes. In vitro studies showed that adipocytes from WT animals can provide ligands for activation of PPARγ and that activation is further boosted following lipolytic stimulation, whereas adipocytes from HSL-/- mice displayed attenuated activation of PPARγ, with no change following lipolytic stimulation. These results suggest that one of the mechanisms by which HSL modulates adipose metabolism is by providing intrinsic ligands or pro-ligands for PPARγ.

  • functional interaction of Hormone Sensitive Lipase and perilipin in lipolysis
    Journal of Lipid Research, 2009
    Co-Authors: Wen Jun Shen, Andrew S Greenberg, Shailja Patel, Fredric B Kraemer, Hideaki Miyoshi
    Abstract:

    Adipocyte lipolysis is controlled by complex interactions of Lipases, cofactors, and structural proteins associated with lipid droplets. Perilipin (Plin) A is a major droplet-associated protein that functions as a scaffold, both suppressing basal and facilitating cAMP-dependent protein kinase (PKA)-stimulated lipolysis. Plin is required for the translocation of Hormone-Sensitive Lipase (HSL) from the cytosol to lipid droplets upon stimulation. In these studies, we provide direct evidence for a physical interaction of HSL with Plin. By coexpressing HSL with truncation mutations of Plin, we demonstrate using coimmunoprecipitation that HSL can interact with an N-terminal region located between amino acids 141 and 200 of Plin A as well as with a C-terminal region located between amino acids 406 and 480. The N-terminal construct, Plin 1-200, which does not associate with lipid droplets but interacts with HSL, can function as a dominant negative for PKA-stimulated lipolysis. Using confocal microscopy of Plin truncations, we demonstrate that sequences between amino acids 463 and 517 may be important for or participate in lipid targeting. The results suggest the translocation of HSL to the lipid droplet occurs by virtue of Plin localization to the surface of lipid droplets and a physical interaction of HSL occurring with sequences within the N-terminal region of Plin.

  • function of Hormone Sensitive Lipase in diacylglycerol protein kinase c pathway
    Diabetes Research and Clinical Practice, 2004
    Co-Authors: Hideo Kanehara, Wen Jun Shen, Fredric B Kraemer, Jinya Suzuki, Yasuo Zenimaru, Sadao Takahashi, Koji Oida, Isamu Miyamori
    Abstract:

    Abstract To explore the functional effects of Hormone-Sensitive Lipase (HSL) in diacylglycerol (DAG) metabolism, Chinese hamster ovary cells were stably transfected with rat HSL cDNA (wt-HSL), inactive mutant S423A-HSL cDNA (S423A) and pcDNA3 vector alone (Ct). [ 14 C ]Glucose-incorporation into triglyceride (TG) was 75% lower in the presence or absence of insulin in cells expressing wt-HSL compared to Ct or S423A. [ 14 C ]Glucose-incorporation into DAG was 33% lower without insulin and 51% lower with insulin in cells expressing wt-HSL compared to Ct or S423A. Insulin stimulated glucose-incorporation into DAG 2.2-fold in S423A and Ct cells, whereas only a 50% increase was observed in cells expressing wt-HSL. PhosphoLipase C-mediated release of DAG from membrane phospholipids was reduced 70% in cells expressing wt-HSL compared to Ct or S423A. Western blot analysis showed that membrane-bound protein kinase C (PKC)-α and -e were decreased 40–50% in cells expressing wt-HSL grown in high glucose with insulin. These data show that HSL potentially hydrolyzes cellular DAG generated either by de novo synthesis from glucose or release from membrane phospholipids by phosphoLipase C, resulting in a reduction in the translocation of DAG-Sensitive PKCs.

  • Hormone Sensitive Lipase is required for high density lipoprotein cholesteryl ester supported adrenal steroidogenesis
    Molecular Endocrinology, 2004
    Co-Authors: Wen Jun Shen, Shailja Patel, Fredric B Kraemer, Junichi Osuga, Kenji Harada, Shun Ishibashi, Salman Azhar
    Abstract:

    Steroid Hormones are synthesized using cholesterol as precursor, with a substantial portion supplied by the selective uptake of lipoprotein-derived cholesteryl esters. Adrenals express a high level of neutral cholesteryl ester hydrolase activity, and recently Hormone-Sensitive Lipase (HSL) was shown to be responsible for most adrenal neutral cholesteryl ester hydrolase activity. To determine the functional importance of HSL in adrenal steroidogenesis, adrenal cells were isolated from control and HSL−/− mice, and the in vitro production of corticosterone was quantified. Results show that, even though adrenal cholesteryl ester content was substantially elevated in both male and female HSL−/− mice, basal corticosterone production was reduced approximately 50%. The maximum corticosterone production induced by dibutyryl cAMP, and lipoproteins was approximately 75–85% lower in adrenal cells from HSL−/− mice compared with control. There is no intrinsic defect in the conversion of cholesterol into steroids in HSL...

Patrice Faure - One of the best experts on this subject based on the ideXlab platform.

  • endothelin regulates intermittent hypoxia induced lipolytic remodelling of adipose tissue and phosphorylation of Hormone Sensitive Lipase
    The Journal of Physiology, 2016
    Co-Authors: Anne Brianconmarjollet, Denis Monneret, Marion Henri, Florence Hazanepuch, Jeanlouis Pepin, Patrice Faure
    Abstract:

    Obstructive sleep apnoea syndrome is characterized by repetitive episodes of upper airway collapse during sleep resulting in chronic intermittent hypoxia (IH). Obstructive sleep apnoea syndrome, through IH, promotes cardiovascular and metabolic disorders. Endothelin-1 (ET-1) secretion is upregulated by IH, and is able to modulate adipocyte metabolism. Therefore, the present study aimed to characterize the role of ET-1 in the metabolic consequences of IH on adipose tissue in vivo and in vitro. Wistar rats were submitted to 14 days of IH-cycles (30 s of 21% FiO2 and 30 s of 5% FiO2 ; 8 h day(-1) ) or normoxia (air-air cycles) and were treated or not with bosentan, a dual type A and B endothelin receptor (ETA-R and ETB-R) antagonist. Bosentan treatment decreased plasma free fatty acid and triglyceride levels, and inhibited IH-induced lipolysis in adipose tissue. Moreover, IH induced a 2-fold increase in ET-1 transcription and ETA-R expression in adipose tissue that was reversed by bosentan. In 3T3-L1 adipocytes, ET-1 upregulated its own and its ETA-R transcription and this effect was abolished by bosentan. Moreover, ET-1 induced glycerol release and inhibited insulin-induced glucose uptake. Bosentan and BQ123 inhibited these effects. Bosentan also reversed the ET-1-induced phosphorylation of Hormone-Sensitive Lipase (HSL) on Ser(660) . Finally, ET-1-induced lipolysis and HSL phosphorylation were also observed under hypoxia. Altogether, these data suggest that ET-1 is involved in IH-induced lipolysis in Wistar rats, and that upregulation of ET-1 production and ETA-R expression by ET-1 itself under IH could amplify its effects. Moreover, ET-1-induced lipolysis could be mediated through ETA-R and activation of HSL by Ser(660) phosphorylation.

  • endothelin regulates intermittent hypoxia induced lipolytic remodelling of adipose tissue and phosphorylation of Hormone Sensitive Lipase
    European Respiratory Journal, 2015
    Co-Authors: Anne Brianconmarjollet, Denis Monneret, Marion Henri, Florence Hazanepuch, Jeanlouis Pepin, Patrice Faure, Diane Godinribuot
    Abstract:

    Obstructive sleep apnea syndrome (OSA) is characterized by repetitive upper airway collapses during sleep inducing chronic intermittent hypoxia (IH). IH promotes adipose tissue remodelling and dyslipidaemia. Endothelin-1 (ET-1) production is upregulated by IH and may participate to changes in adipose tissue biology. Wistar rats were submitted to 14 days of IH (60-sec cycles alternating 21 and 5% FiO 2 , 8h/day) or control normoxia and treated or not with bosentan, a dual type A (ETA-R) and B (ETB-R) endothelin receptor antagonist. IH induced a lipolytic remodelling and a 2-fold increase in ET-1 transcription and ETA-R expression in adipose tissue that were reversed by bosentan. In 3T3-L1 adipocytes, ET-1 induced an upregulation of its own and of ETA-R transcription. Moreover, ET-1 promoted a glycerol release inhibited by bosentan and BQ123 (ETA-R antagonist) but not by BQ788 (ETB-R antagonist). Finally, bosentan reversed the ET-1-induced phosphorylation of Hormone-Sensitive Lipase (HSL) on Serine 660. ET-1 is thus involved in IH-induced lipolysis in Wistar rats, and upregulation of ET-1 production and ETA-R expression by ET-1 itself under IH could amplify its effects. ET-1-induced lipolysis appears to be mediated through ETA receptors and the activation of HSL by Serine 660 phosphorylation.

Anne Brianconmarjollet - One of the best experts on this subject based on the ideXlab platform.

  • endothelin regulates intermittent hypoxia induced lipolytic remodelling of adipose tissue and phosphorylation of Hormone Sensitive Lipase
    The Journal of Physiology, 2016
    Co-Authors: Anne Brianconmarjollet, Denis Monneret, Marion Henri, Florence Hazanepuch, Jeanlouis Pepin, Patrice Faure
    Abstract:

    Obstructive sleep apnoea syndrome is characterized by repetitive episodes of upper airway collapse during sleep resulting in chronic intermittent hypoxia (IH). Obstructive sleep apnoea syndrome, through IH, promotes cardiovascular and metabolic disorders. Endothelin-1 (ET-1) secretion is upregulated by IH, and is able to modulate adipocyte metabolism. Therefore, the present study aimed to characterize the role of ET-1 in the metabolic consequences of IH on adipose tissue in vivo and in vitro. Wistar rats were submitted to 14 days of IH-cycles (30 s of 21% FiO2 and 30 s of 5% FiO2 ; 8 h day(-1) ) or normoxia (air-air cycles) and were treated or not with bosentan, a dual type A and B endothelin receptor (ETA-R and ETB-R) antagonist. Bosentan treatment decreased plasma free fatty acid and triglyceride levels, and inhibited IH-induced lipolysis in adipose tissue. Moreover, IH induced a 2-fold increase in ET-1 transcription and ETA-R expression in adipose tissue that was reversed by bosentan. In 3T3-L1 adipocytes, ET-1 upregulated its own and its ETA-R transcription and this effect was abolished by bosentan. Moreover, ET-1 induced glycerol release and inhibited insulin-induced glucose uptake. Bosentan and BQ123 inhibited these effects. Bosentan also reversed the ET-1-induced phosphorylation of Hormone-Sensitive Lipase (HSL) on Ser(660) . Finally, ET-1-induced lipolysis and HSL phosphorylation were also observed under hypoxia. Altogether, these data suggest that ET-1 is involved in IH-induced lipolysis in Wistar rats, and that upregulation of ET-1 production and ETA-R expression by ET-1 itself under IH could amplify its effects. Moreover, ET-1-induced lipolysis could be mediated through ETA-R and activation of HSL by Ser(660) phosphorylation.

  • endothelin regulates intermittent hypoxia induced lipolytic remodelling of adipose tissue and phosphorylation of Hormone Sensitive Lipase
    European Respiratory Journal, 2015
    Co-Authors: Anne Brianconmarjollet, Denis Monneret, Marion Henri, Florence Hazanepuch, Jeanlouis Pepin, Patrice Faure, Diane Godinribuot
    Abstract:

    Obstructive sleep apnea syndrome (OSA) is characterized by repetitive upper airway collapses during sleep inducing chronic intermittent hypoxia (IH). IH promotes adipose tissue remodelling and dyslipidaemia. Endothelin-1 (ET-1) production is upregulated by IH and may participate to changes in adipose tissue biology. Wistar rats were submitted to 14 days of IH (60-sec cycles alternating 21 and 5% FiO 2 , 8h/day) or control normoxia and treated or not with bosentan, a dual type A (ETA-R) and B (ETB-R) endothelin receptor antagonist. IH induced a lipolytic remodelling and a 2-fold increase in ET-1 transcription and ETA-R expression in adipose tissue that were reversed by bosentan. In 3T3-L1 adipocytes, ET-1 induced an upregulation of its own and of ETA-R transcription. Moreover, ET-1 promoted a glycerol release inhibited by bosentan and BQ123 (ETA-R antagonist) but not by BQ788 (ETB-R antagonist). Finally, bosentan reversed the ET-1-induced phosphorylation of Hormone-Sensitive Lipase (HSL) on Serine 660. ET-1 is thus involved in IH-induced lipolysis in Wistar rats, and upregulation of ET-1 production and ETA-R expression by ET-1 itself under IH could amplify its effects. ET-1-induced lipolysis appears to be mediated through ETA receptors and the activation of HSL by Serine 660 phosphorylation.