Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase

Khoo, John C.; Sperry, Pamela J.; Gill, Gordon N.; Steinberg, Daniel

doi:10.1073/pnas.74.11.4843

Cited by 55 publications

(11 citation statements)

References 35 publications

(16 reference statements)

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“…Indeed, Rp-8-pCPTcGMPS dramatically diminished the ANP-induced lipolysis and decreased the ANP-mediated phosphorylation of HSL. This result is consistent and provides a biologically relevant role to early data demonstrating, on a cell-free system, the phosphorylation and activation of HSL by cGK (43,44). Further studies should be performed to identify which phosphorylated serine residues could be involved in the HSL and perilipin phosphorylation during ANP stimulation of human adipocytes.…”

Section: Cgmp/cgki Involvement In Np-mediated Hsl Phosphorylationsupporting

confidence: 58%

Involvement of a cGMP-dependent Pathway in the Natriuretic Peptide-mediated Hormone-sensitive Lipase Phosphorylation in Human Adipocytes

Sengenès

Bouloumié

Hauner³

et al. 2003

Journal of Biological Chemistry

232

157

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Our previous studies have demonstrated that natriuretic peptides (NPs), peptide hormones with natriuretic, diuretic, and vasodilating properties, exert a potent control on the lipolysis in human adipocytes via the activation of the type A guanylyl cyclase receptor (1, 2). In the current study we investigated the intracellular mechanisms involved in the NP-stimulated lipolytic effect in human preadipocytes and adipocytes. We demonstrate that the atrial NP (ANP)-induced lipolysis in human adipocytes was associated with an enhanced serine phosphorylation of the hormone-sensitive lipase (HSL). Both ANP-mediated lipolysis and HSL phosphorylation were inhibited in the presence of increasing concentrations of the guanylyl cyclase inhibitor LY-83583. ANP did not modulate the activity of the cAMP-dependent protein kinase (PKA). Moreover, H-89, a PKA inhibitor, did not affect the ANP-induced lipolysis. On primary cultures of human preadipocytes, the ANP-mediated lipolytic effect was dependent on the differentiation process. On differentiated human preadipocytes, ANPmediated lipolysis, associated with an increased phosphorylation of HSL and of perilipin A, was strongly decreased by treatment with the inhibitor of the cGMPdependent protein kinase I (cGKI), Rp-8-pCPT-cGMPS. Thus, ANP-induced lipolysis in human adipocytes is a cGMP-dependent pathway that induces the phosphorylation of HSL and perilipin A via the activation of cGKI. The present study shows that lipolysis in human adipocytes can be controlled by an independent cGKI-mediated signaling as well as by the classical cAMP/PKA pathway.Natriuretic peptides (NPs) 1 are a family of polypeptide hormones (atrial NP (ANP), brain NP, and C-type NP) that regulate blood pressure, natriuresis, diuresis, together with renin and aldosterone release by direct effects on the kidney, the adrenal glands, and the systemic vasculature (3-5). NPs signaling operates through two groups of cell surface receptors: the guanylyl cyclase (GC) receptors named GC-A and GC-B (6, 7) and the clearance receptor or type C NP receptor (NPr-C) without intrinsic GC activity (8 -10). The cGMP produced after the activation of GC-coupled receptors has multiple effectors within the cell, including the families of cGMPdependent protein kinases (cGK), cGMP-stimulated/cGMPinhibited phosphodiesterases (PDEs), cGMP-gated cation channels, and, in some cases, cAMP-dependent protein kinase A (PKA) (11,12).In addition to their renal, adrenal, and vascular effects, NPs may affect the metabolism of human adipocytes. In previous studies, we have demonstrated that ANP and brain NP, but not C-type NP, are potent stimulators of human fat cell lipolysis (1, 2). Clinical studies have validated their action in vivo (13,14). However, the intracellular pathway involved in the NP-stimulated lipolytic effect still remained to be characterized. Former studies on human adipocytes have shown the essential role of cAMP in the modulation of the lipolytic pathway. Indeed, the main lipolytic regulators in human fat cells, i.e. catech...

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Section: Cgmp/cgki Involvement In Np-mediated Hsl Phosphorylationsupporting

confidence: 58%

Involvement of a cGMP-dependent Pathway in the Natriuretic Peptide-mediated Hormone-sensitive Lipase Phosphorylation in Human Adipocytes

Sengenès

Bouloumié

Hauner³

et al. 2003

Journal of Biological Chemistry

232

157

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“…5 This finding in isolated human fat cells confirms early data from a rat cell-free system where the phosphorylation of HSL by PKG was reported. 83,84 Recent studies have shown a role for the MAP-kinases in the control of lipolysis by TNF-␣ in human fat cells. 85,86 ANP does not modulate the phosphorylation of extracellular signal regulated kinase (ERK)-1/2 and p38 MAP-kinase.…”

Section: Lipolytic Effect Of Natriuretic Peptidesmentioning

confidence: 99%

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Lafontan

Moro

Sengenès

et al. 2005

ATVB

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Abstract-In normal and obese humans, lipid mobilization and systemic nonesterified fatty acid levels are thought to be acutely controlled by catecholamines (ie, epinephrine and norepinephrine) and insulin. Natriuretic peptides (NPs) are known to play a key role in the regulation of salt and water balance and blood pressure homeostasis. They are involved in the pathophysiology of hypertension and heart failure. (ATP III). The NCEP definition of the metabolic syndrome includes 3 or more of the following: abdominal obesity, defined as waist circumference Ն102 cm in men and Ͼ88 cm in women; elevated triglyceride concentration Ն150 mg/dL, low HDL cholesterol (Ͻ40 mg/dL in men and Ͻ50 mg/dL in women); elevated fasting plasma glucose level (Ն110 mg/dL); and elevated blood pressure (Ն130/85 mm Hg). 1 The presence of abdominal obesity is more closely associated with the metabolic risk factors than body mass index. The prevalence of the metabolic syndrome increases with age. Obesity interferes with many metabolic pathways which underlie numerous potential risk factors. It is very difficult to differentiate between the major and minor factors, and some remain to be discovered. 2 This complexity leaves the area open and challenges basic and clinical researchers to uncover novel metabolic pathways. The discovery that cardiac natriuretic peptides (NPs) control human fat cell function is a provocative observation which reveals an unsuspected link between heart and adipose tissue. NPs exert potent lipolytic effects (eg, stimulation of hydrolysis of triacylglycerols stored in adipocytes) in isolated human fat cells. 3 When administered intravenously, they potently increase plasma glycerol and nonesterified fatty acid (NEFA) levels; in other words they stimulate lipid mobilization. 4 Before the discovery of the NP pathway, catecholamines and insulin were considered to be the major acute regulators of lipid mobilization in humans: they both act through a cAMP-dependent regulation of lipolysis. In contrast, NPs activate a 3Ј, 5Ј-cyclic guanosine monophosphate (cGMP)-dependent pathway that is completely independent from the cAMP-dependent pathway. 5 The NPs may represent a promising new pathway contributing to the control of lipid mobilization in humans in physiological and pathological conditions. The introductory section

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“…HSL, activatable by cGMP-dependent protein kinase (19), regulates cellular lipid homeostasis and catalyzes the hydrolysis of stored triacylglycerol (55). ANP (100 nM and 1 M) evoked marked increases in activated phospho-HSL levels in islets after only 30 min of stimulation (Fig.…”

Section: Resultsmentioning

confidence: 99%

“…ANP and cGMP-dependent protein kinase activate HSL in several tissues (19,42). HSL is expressed as a doublet in rat islets (55), and ANP induced a rapid activation of islet HSL, which would produce free fatty acids due to the hydrolysis and depletion of triacylglycerol.…”

Section: E440 Anp Inhibits Atp and Insulin Secretion In Isletsmentioning

confidence: 99%

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Long-term treatment with atrial natriuretic peptide inhibits ATP production and insulin secretion in rat pancreatic islets

You

Laychock

2011

American Journal of Physiology-Endocrinology and Metabolism

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You H, Laychock SG. Long-term treatment with atrial natriuretic peptide inhibits ATP production and insulin secretion in rat pancreatic islets. Am J Physiol Endocrinol Metab 300: E435-E444, 2011. First published October 19, 2010 doi:10.1152/ajpendo.00398.2010.-Atrial natriuretic peptide (ANP) levels correlate with hyperglycemia in diabetes mellitus, but ANP effects on pancreatic islet ␤-cell insulin secretion are controversial. ANP was investigated for short-and long-term effects on insulin secretion and mechanisms regulating secretion in isolated rat pancreatic islets. A 3-h incubation with ANP did not affect basal or glucose-stimulated islet insulin secretion. However, 7-day culture of islets with 5.5 mM glucose and ANP (1 nM -1 M) markedly inhibited subsequent glucose (11 mM)-stimulated insulin secretion; total islet insulin content was not affected. Following ANP removal for 24 h, the islet insulin-secretory response to glucose was restored. The insulin-secretory response to other insulin secretagogues, including ␣-ketoisocaproic acid, forskolin, potassium chloride, and ionomycin were also markedly inhibited by chronic exposure to ANP. However, the combination of potassium chloride and ␣-ketoisocaproic acid was sufficient to overcome the inhibitory effects of ANP on insulin secretion. The glucose-stimulated increases in islet ATP levels and the ATP/ADP ratio were completely inhibited in ANP 7-day-treated islets vs. control; removal of ANP for 24 h partially restored the glucose response. ANP did not affect islet glycolysis. ANP significantly increased levels of islet activated hormone-sensitive lipase and the expression of uncoupling protein-2 and peroxisome proliferator-activated receptor-␦ and -␣. Although islet ANP-binding natriuretic peptide receptor-A levels were reduced to 60% of control after 7-day culture with ANP, the ANP-stimulated cGMP levels remained similar to control islet levels. Thus, long-term exposure to ANP inhibits glucose-stimulated insulin secretion and ATP generation in isolated islets.

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Activation of hormone-sensitive lipase and phosphorylase kinase by purified cyclic GMP-dependent protein kinase

Cited by 55 publications

References 35 publications

Involvement of a cGMP-dependent Pathway in the Natriuretic Peptide-mediated Hormone-sensitive Lipase Phosphorylation in Human Adipocytes

Involvement of a cGMP-dependent Pathway in the Natriuretic Peptide-mediated Hormone-sensitive Lipase Phosphorylation in Human Adipocytes

An Unsuspected Metabolic Role for Atrial Natriuretic Peptides

Long-term treatment with atrial natriuretic peptide inhibits ATP production and insulin secretion in rat pancreatic islets

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