C3, hormone-sensitive lipase, and peroxisome proliferator-activated receptor [gamma ] expression in adipose tissue of familial combined hyperlipidemia patients

Metabolism ◽  
2002 ◽  
Vol 51 (5) ◽  
pp. 664-670 ◽  
Author(s):  
Kati Ylitalo ◽  
Ilpo Nuotio ◽  
Jorma Viikari ◽  
Johan Auwerx ◽  
Hubert Vidal ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Familial Combined Hyperlipidemia ◽  
Peroxisome Proliferator Activated Receptor ◽  
Hormone Sensitive

Effects of DHEA on metabolic and endocrine functions of adipose tissue

2013 ◽  
Vol 14 (2) ◽  
Author(s):  
Joanna Karbowska ◽  
Zdzislaw Kochan
Keyword(s):  
Adipose Tissue ◽  
Human Adipose Tissue ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Tissue Mass ◽  
Triacylglycerol Hydrolysis ◽  
Proliferation And Differentiation ◽  
Hormone Sensitive ◽  
Hormone Biosynthesis ◽  
Peroxisome Proliferator Activated Receptors

AbstractDehydroepiandrosterone (DHEA) and its sulfate ester, DHEAS, are the major circulating adrenal steroids and serve as substrates for sex hormone biosynthesis. DHEA is effectively taken up by adipose tissue, where the concentrations of free DHEA are four to ten times higher than those found in the circulation. DHEA reduces adipose tissue mass and inhibits the proliferation and differentiation of adipocytes; it may also protect against obesity by lowering the activity of stearoyl-CoA desaturase 1 in fat cells. Recent studies demonstrate that DHEA stimulates triacylglycerol hydrolysis in adipose tissue by increasing the expression and activity of adipose triglyceride lipase and hormone-sensitive lipase, the key enzymes of lipolysis. DHEA has been shown to modulate insulin signaling pathways, enhance glucose uptake in adipocytes, and increase insulin sensitivity in patients with DHEA deficiency or abnormal glucose tolerance. Additionally, by suppressing the activity of 11β-hydroxysteroid dehydrogenase 1 in adipocytes, DHEA may promote intra-adipose inactivation of cortisol to cortisone. Several studies have demonstrated that DHEA may also regulate the expression and secretion of adipokines such as leptin, adiponectin, and resistin. The effects of DHEA on adipokine expression in adipose tissue are depot-specific, with visceral fat being the most responsive. The mechanisms underlying DHEA actions in adipose tissue are still unclear; however, they involve nuclear receptors such as androgen receptor and peroxisome proliferator-activated receptors γ and α. Because clinical trials investigating the effects of DHEA failed to yield consistent results, further studies are needed to clarify the role of DHEA in the regulation of human adipose tissue physiology.

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 Developmental Programming: Differential Effects of Prenatal Testosterone Excess on Insulin Target Tissues

2010 ◽  
Vol 31 (5) ◽  
pp. 775-775
Author(s):  
Shadia E. Nada ◽  
Robert C. Thompson ◽  
Vasantha Padmanabhan
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Glycogen Synthase ◽  
Hormone Sensitive Lipase ◽  
Initiation Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peripheral Tissues ◽  
Prenatal Testosterone

Polycystic ovarian syndrome (PCOS) is the leading cause of infertility in reproductive-aged women with the majority manifesting insulin resistance. To delineate the causes of insulin resistance in women with PCOS, we determined changes in the mRNA expression of insulin receptor (IR) isoforms and members of its signaling pathway in tissues of adult control (n = 7) and prenatal testosterone (T)-treated (n = 6) sheep (100 mg/kg twice a week from d 30-90 of gestation), the reproductive/metabolic characteristics of which are similar to women with PCOS. Findings revealed that prenatal T excess reduced (P < 0.05) expression of IR-B isoform (only isoform detected), insulin receptor substrate-2 (IRS-2), protein kinase B (AKt), peroxisome proliferator-activated receptor-γ (PPARγ), hormone-sensitive lipase (HSL), and mammalian target of rapamycin (mTOR) but increased expression of rapamycin-insensitive companion of mTOR (rictor), and eukaryotic initiation factor 4E (eIF4E) in the liver. Prenatal T excess increased (P < 0.05) the IR-A to IR-B isoform ratio and expression of IRS-1, glycogen synthase kinase-3α and -β (GSK-3α and -β), and rictor while reducing ERK1 in muscle. In the adipose tissue, prenatal T excess increased the expression of IRS-2, phosphatidylinositol 3-kinase (PI3K), PPARγ, and mTOR mRNAs. These findings provide evidence that prenatal T excess modulates in a tissue-specific manner the expression levels of several genes involved in mediating insulin action. These changes are consistent with the hypothesis that prenatal T excess disrupts the insulin sensitivity of peripheral tissues, with liver and muscle being insulin resistant and adipose tissue insulin sensitive.

scholarly journals Unripe Rubus coreanus Miquel Extract Containing Ellagic Acid Promotes Lipolysis and Thermogenesis In Vitro and In Vivo

Molecules ◽  
2020 ◽  
Vol 25 (24) ◽  
pp. 5954
Author(s):  
Kyeong Jo Kim ◽  
Eui-Seon Jeong ◽  
Ki Hoon Lee ◽  
Ju-Ryun Na ◽  
Soyi Park ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
White Adipose Tissue ◽  
Ellagic Acid ◽  
Uncoupling Protein ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Rubus Coreanus ◽  
Associated Proteins

Previously, we demonstrated that a 5% ethanol extract of unripe Rubus coreanus (5-uRCK) and ellagic acid has hypocholesterolemic and antiobesity activity, at least partially mediated by the downregulation of adipogenic and lipogenic gene expression in high-fat diet (HFD)-fed animals. The present study investigated the thermogenic and lipolytic antiobesity effects of 5-uRCK and ellagic acid in HFD-induced obese C57BL/6 mice and explored its mechanism of action. Mice fed an HFD received 5-uRCK or ellagic acid as a post-treatment or pretreatment. Both post-treated and pretreated mice showed significant reductions in body weight and adipose tissue mass compared to the HFD-fed mice. The protein levels of lipolysis-associated proteins, such as adipose triglyceride lipase (ATGL), phosphorylated hormone-sensitive lipase (p-HSL), and perilipin1 (PLIN1), were significantly increased in both the 5-uRCK- and ellagic acid-treated mouse epididymal white adipose tissue (eWAT). Additionally, thermogenesis-associated proteins, such as peroxisome proliferator-activated receptor α (PPARα), carnitine palmitoyl transferase-1 (CPT1), uncoupling protein 1 (UCP1), and peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), in inguinal white adipose tissue (ingWAT) were clearly increased in both the 5-uRCK- and ellagic acid-treated mice compared to HFD-fed mice. These results suggest that 5-uRCK and ellagic acid are effective for suppressing body weight gain and enhancing the lipid profile.

scholarly journals Heterogeneity in the physiological states and pharmacological responses of differentiating 3T3-L1 preadipocytes

2009 ◽  
Vol 187 (3) ◽  
pp. 375-384 ◽  
Author(s):  
Lit-Hsin Loo ◽  
Hai-Jui Lin ◽  
Dinesh K. Singh ◽  
Kathleen M. Lyons ◽  
Steven J. Altschuler ◽  
...  
Keyword(s):  
Immunofluorescence Microscopy ◽  
Hormone Sensitive Lipase ◽  
Molecular Heterogeneity ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specific Effects ◽  
Enhancer Binding Protein ◽  
Perilipin A ◽  
Pparγ Agonists ◽  
Hormone Sensitive

Increases in key components of adipogenesis and lipolysis pathways correlate at the population-averaged level during adipogenesis. However, differentiating preadipocytes are highly heterogeneous in cellular and lipid droplet (LD) morphologies, and the degree to which individual cells follow population-averaged trends is unclear. In this study, we analyze the molecular heterogeneity of differentiating 3T3-L1 preadipocytes using immunofluorescence microscopy. Unexpectedly, we only observe a small percentage of cells with high simultaneous expression of markers for adipogenesis (peroxisome proliferator-activated receptor γ [PPARγ], CCAAT/enhancer-binding protein α, and adiponectin) and lipid accumulation (hormone-sensitive lipase, perilipin A, and LDs). Instead, we identify subpopulations of cells with negatively correlated expressions of these readouts. Acute perturbation of adipocyte differentiation with PPARγ agonists, forskolin, and fatty acids induced subpopulation-specific effects, including redistribution of the percentage of cells in observed subpopulations and differential expression levels of PPARγ. Collectively, our results suggested that heterogeneity observed during 3T3-L1 adipogenesis reflects a dynamic mixture of subpopulations with distinct physiological states.

scholarly journals Alisol A 24-acetate stimulates lipolysis in 3 T3-L1 adipocytes

2021 ◽  
Vol 21 (1) ◽  
Author(s):  
Hai-xia Lou ◽  
Wen-cheng Fu ◽  
Jia-xiang Chen ◽  
Tian-tian Li ◽  
Ying-ying Jiang ◽  
...  
Keyword(s):  
Biological Activities ◽  
Quantitative Polymerase Chain Reaction ◽  
Underlying Mechanism ◽  
Hormone Sensitive Lipase ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Protein Levels ◽  
Alisma Orientale ◽  
Perilipin A ◽  
Hormone Sensitive

Abstract Background Alisol A 24-acetate (AA-24-a), one of the main active triterpenes isolated from the well-known medicinal plant Alisma orientale (Sam.) Juz., exhibits multiple biological activities including hypolipidemic activity. However, its effect on lipid metabolism in adipocytes remains unclear. The present study aimed to clarify the effect of AA-24-a on adipocyte lipolysis and to determine its potential mechanism of action using 3 T3-L1 cells. Methods We assayed the release of glycerol into culture medium of 3 T3-L1 cells under treatment with AA-24-a. Protein and mRNA expression and phosphorylation levels of the main lipases and kinases involved in lipolysis regulation were determined by quantitative polymerase chain reaction and western blotting. Specific inhibitors of protein kinase A (PKA; H89) and extracellular signal-regulated kinase (ERK; PD98059), which are key enzymes in relevant signaling pathways, were used to examine their roles in AA-24-a-stimulated lipolysis. Results AA-24-a significantly stimulated neutral lipolysis in fully differentiated adipocytes. To determine the underlying mechanism, we assessed the changes in mRNA and protein levels of key lipolysis-related genes in the presence or absence of H89 and PD98059. Both inhibitors reduced AA-24-a-induced lipolysis. Moreover, pretreatment with H89 attenuated AA-24-a-induced phosphorylation of hormone-sensitive lipase at Ser660, while pretreatment with PD98059 attenuated AA-24-a-induced downregulation of peroxisome proliferator-activated receptor-γ and perilipin A. Conclusions Our results indicate that AA-24-a promoted neutral lipolysis in 3 T3-L1 adipocytes by activating PKA-mediated phosphorylation of hormone-sensitive lipase and ERK- mediated downregulation of expression of perilipin A.

scholarly journals Developmental Programming: Differential Effects of Prenatal Testosterone Excess on Insulin Target Tissues

Endocrinology ◽  
2010 ◽  
Vol 151 (11) ◽  
pp. 5165-5173 ◽  
Author(s):  
Shadia E. Nada ◽  
Robert C. Thompson ◽  
Vasantha Padmanabhan
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Receptor ◽  
Glycogen Synthase ◽  
Hormone Sensitive Lipase ◽  
Initiation Factor ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Peripheral Tissues ◽  
Prenatal Testosterone

Polycystic ovarian syndrome (PCOS) is the leading cause of infertility in reproductive-aged women with the majority manifesting insulin resistance. To delineate the causes of insulin resistance in women with PCOS, we determined changes in the mRNA expression of insulin receptor (IR) isoforms and members of its signaling pathway in tissues of adult control (n = 7) and prenatal testosterone (T)-treated (n = 6) sheep (100 mg/kg twice a week from d 30–90 of gestation), the reproductive/metabolic characteristics of which are similar to women with PCOS. Findings revealed that prenatal T excess reduced (P < 0.05) expression of IR-B isoform (only isoform detected), insulin receptor substrate-2 (IRS-2), protein kinase B (AKt), peroxisome proliferator-activated receptor-γ (PPARγ), hormone-sensitive lipase (HSL), and mammalian target of rapamycin (mTOR) but increased expression of rapamycin-insensitive companion of mTOR (rictor), and eukaryotic initiation factor 4E (eIF4E) in the liver. Prenatal T excess increased (P < 0.05) the IR-A to IR-B isoform ratio and expression of IRS-1, glycogen synthase kinase-3α and -β (GSK-3α and -β), and rictor while reducing ERK1 in muscle. In the adipose tissue, prenatal T excess increased the expression of IRS-2, phosphatidylinositol 3-kinase (PI3K), PPARγ, and mTOR mRNAs. These findings provide evidence that prenatal T excess modulates in a tissue-specific manner the expression levels of several genes involved in mediating insulin action. These changes are consistent with the hypothesis that prenatal T excess disrupts the insulin sensitivity of peripheral tissues, with liver and muscle being insulin resistant and adipose tissue insulin sensitive.

scholarly journals Peroxisome Proliferator-Activated Receptor-γ Transcriptionally Up-Regulates Hormone-Sensitive Lipase via the Involvement of Specificity Protein-1

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 875-884 ◽  
Author(s):  
Tuo Deng ◽  
Song Shan ◽  
Ping-Ping Li ◽  
Zhu-Fang Shen ◽  
Xian-Ping Lu ◽  
...  
Keyword(s):  
Specific Inhibitor ◽  
Binding Activity ◽  
Hormone Sensitive Lipase ◽  
Proximal Promoter ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Specificity Protein 1 ◽  
Pparγ Agonists ◽  
Hormone Sensitive ◽  
Specificity Protein

Both peroxisome proliferator-activated receptor (PPAR)-γ and hormone-sensitive lipase (HSL) play important roles in lipid metabolism and insulin sensitivity. We demonstrate that expression of the HSL gene is up-regulated by PPARγ and PPARγ agonists (rosiglitazone and pioglitazone) in the cultured hepatic cells and differentiating preadipocytes. Rosiglitazone treatment also results in up-regulation of the HSL gene in liver and skeleton muscle from an experimental obese rat model, accompanied by the decreased triglyceride content in these tissues. The proximal promoter (−87 bp of the human HSL gene) was found to be essential for PPARγ-mediated transactivating activity. This important promoter region contains two GC-boxes and binds the transcription factor specificity protein-1 (Sp1) but not PPARγ. The Sp1-promoter binding activity can be endogenously enhanced by PPARγ and rosiglitazone, as demonstrated by analysis of EMSA and chromatin immunoprecipitation assay. Mutations in the GC-box sequences reduce the promoter binding activity of Sp1 and the transactivating activity of PPARγ. In addition, mithramycin A, the specific inhibitor for Sp1-DNA binding activity, abolishes the PPARγ-mediated up-regulation of HSL. These results indicate that PPARγ positively regulates the HSL gene expression, and up-regulation of HSL by PPARγ requires the involvement of Sp1. Taken together, this study suggests that HSL may be a newly identified PPARγ target gene, and up-regulation of HSL may be an important mechanism involved in action of PPARγ agonists in type 2 diabetes.

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