Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes

Plée-Gautier, Emmanuelle; Grober, Jacques; Duplus, Eric; Langin, Dominique; Forest, Claude

doi:10.1042/bj3181057

Cited by 38 publications

(35 citation statements)

References 44 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Slavin et al 44 incubated primary cultures of rat adipocytes with adrenaline or glucagon and there was an increase in medium glycerol but no change in HSL mRNA levels. Ple Âe-Gautier et al 13 found that treating adipocytes with cAMP analogues considerably decreased HSL mRNA. The similarity between the Ple Âe-Gautier results 13 and ours reinforces the idea that the procyanidins mediate this effect by modulating cAMP levels.…”

Section: Resultsmentioning

confidence: 99%

“…Ple Âe-Gautier et al 13 found that treating adipocytes with cAMP analogues considerably decreased HSL mRNA. The similarity between the Ple Âe-Gautier results 13 and ours reinforces the idea that the procyanidins mediate this effect by modulating cAMP levels. Some authors 13 postulate that long-term cAMP treatment of adipocytes induces a counter-regulatory process that reduces HSL content and, ultimately, limits the depletion of fatty acids from stored triacylglycerol.…”

Section: Resultsmentioning

confidence: 99%

“…10 Many therapeutic agents cause direct lipolysis or anti-lipolysis in adipocytes, 11,12 and short-term hormonal regulation of HSL activity is well characterized, whereas little is known about how HSL gene expression is controlled. 13 Some¯avonoids are potent inhibitors of protein kinases (PKA, PKC, MLCK, CDPK), 14 and a number of procyanidin preparations from a variety of plants are among the most potent inhibitors of eukaryote protein kinases yet found. 15 While there are many studies of the¯avonol quercetin and its glycosides, less is known about procyanidins that are found in large quantities in grapes and wine.…”

Section: Introductionmentioning

confidence: 99%

See 2 more Smart Citations

Changes in lipolysis and hormone-sensitive lipase expression caused by procyanidins in 3T3-L1 adipocytes

et al. 2000

View full text Add to dashboard Cite

OBJECTIVE: To ®nd out whether lipid stores are in¯uenced by phenolic compounds in wine. DESIGN: Differentiated 3T3-L1 cells were treated with catechin, epicatechin or procyanidin extracts with different degrees of polymerization at 150 m mM for different periods of time (0.5 ± 24 h). SUBJECTS: Cell line 3T3-L1. MEASUREMENTS: Cellular viability, glycerol-3-phosphate dehydrogenase activity, glycerol release in the medium, HSL mRNA levels, triacylglycerols and protein. RESULTS: Catechin, epicatechin and procyanidin extracts were not toxic for the 3T3-L1 cells in the conditions assayed. Glycerol-3-phosphate dehydrogenase activity was markedly decreased by 150 m mM procyanidin extracts. The release of glycerol into the medium was increased in 150 m mM procyanidin extract-treated cells and reached a plateau after 15 h exposure. Procyanidins caused a time-dependent reduction in the HSL mRNA levels. CONCLUSIONS: These results suggest that procyanidins from grape and wine affect lipid metabolism whilst their monomers (catechin and epicatechin) do not. This effect is more pronounced when the degree of polymerization is higher. Procyanidin extracts cause a time-dependent reduction in the HSL mRNA levels, inhibit triacylglycerol synthesis and also favour triacylglycerol hydrolysis until the HSL mRNA had reached very low levels.

show abstract

Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Changes in lipolysis and hormone-sensitive lipase expression caused by procyanidins in 3T3-L1 adipocytes

et al. 2000

View full text Add to dashboard Cite

show abstract

“…Insulin deficiency and hyperglycemia could both account for the upregulation of HSL expression in diabetes. Insulin per se had no effect on HSL mRNA concentrations in 3T3-F442A murine adipocytes (12). However, in this cellular model, glucose deprivation resulted in a twofold decrease in HSL mRNA and total activity levels (13).…”

mentioning

confidence: 96%

Transcriptional Regulation of Adipocyte Hormone-Sensitive Lipase by Glucose

et al. 2002

Self Cite

View full text Add to dashboard Cite

Hormone-sensitive lipase (HSL) catalyzes the ratelimiting step in the mobilization of fatty acids from adipose tissue, thus determining the supply of energy substrates in the body. HSL mRNA was positively regulated by glucose in human adipocytes. Pools of stably transfected 3T3-F442A adipocytes were generated with human adipocyte HSL promoter fragments from ؊2,400/ ؉38 to ؊31/؉38 bp linked to the luciferase gene. A glucose-responsive region was mapped within the proximal promoter (؊137 bp). Electromobility shift assays showed that upstream stimulatory factor (USF)-1 and USF2 and Sp1 and Sp3 bound to a consensus E-box and two GC-boxes in the ؊137-bp region. Cotransfection of the ؊137/؉38 construct with USF1 and USF2 expression vectors produced enhanced luciferase activity. Moreover, HSL mRNA levels were decreased in USF1-and USF2-deficient mice. Site-directed mutagenesis of the HSL promoter showed that the GC-boxes, although contributing to basal promoter activity, were dispensable for glucose responsiveness. Mutation of the E-box led to decreased promoter activity and suppression of the glucose response. Analogs and metabolites were used to determine the signal metabolite of the glucose response. The signal is generated downstream of glucose-6-phosphate in the glycolytic pathway before the triose phosphate step. Diabetes 51:293-300, 2002 H ormone-sensitive lipase (HSL) is a key enzyme for the hydrolysis of adipose tissue triacylglycerol into fatty acids that are the major source of body energy in the absence of dietary lipids. Catecholamines and insulin are important regulators of lipolysis in adipocytes through a modulation of intracellular cAMP levels and reversible phosphorylation of HSL (1). The lipase is thought to catalyze the rate-limiting step in cAMP-dependent lipolysis. In agreement, a strong linear correlation was found between HSL protein levels and the maximum lipolytic capacity of human subcutaneous adipocytes stimulated by a ␤-adrenergic agonist (2). Moreover, targeted disruption of the HSL gene in the mouse results in blunted ␤-adrenergic agonist-induced lipolysis (3,4). Clinical studies also support a role for HSL as a limiting factor in adipose tissue lipolysis and show that, besides the short-term modulation of activity by phosphorylation, variations in HSL expression are associated with changes in lipolytic capacity. Indeed, obese patients and normal-weight subjects with a family trait for obesity show decreased maximal lipolytic effect of catecholamines and blunted HSL expression (5,6). Furthermore, genetic studies suggest that HSL participates in the polygenic background of obesity and type 2 diabetes (7,8).Increased mobilization of fatty acids from adipose tissue stores in diabetic patients leads to high free fatty acid concentrations that contribute to the development of ketoacidosis, a major acute complication of type 1 diabetes (9). Several mechanisms may account for the enhanced lipolysis. Hypoinsulinemia and an increase in the concentrations of stimulatory hormones stimulate HSL activ...

show abstract

“…In the adipocyte line 3T3-F442A, stimulation of the PKA pathway results in inhibition of transcription of the LIPE gene, encoding HSL (Plee-Gautier et al 1996). On the contrary, in Leydig cells, human chorionic gonadotrophin acting through the PKA pathway induces expression of this gene (Kraemer et al 1993).…”

Section: Introductionmentioning

confidence: 99%

Transcription of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase is regulated by SF-1 in human adrenocortical cells: involvement of protein kinase A signal transduction pathway

Hołysz¹,

Derebecka-Holysz²,

Trzeciak³

2010

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

The study was designed to elucidate the influence of the protein kinase A (PKA) signal transduction pathway on transcription of the LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase (HSL) in H295R cells. HSL is one of the key enzymes involved in steroid hormone synthesis, and ACTH, with mediation of the PKA pathway, increases its activity. However, the mode of regulation of LIPE gene expression by ACTH remains unknown. It was found that stimulation of the PKA pathway by the adenylyl cyclase activator, forskolin, caused a twofold increase in LIPE transcript accompanied by appreciable rise in the protein product of the gene and cortisol output. RNA polymerase II inhibitor abolished, and protein synthesis inhibitor attenuated this effect. Forskolin and PKA catalytic subunit increased transcriptional activity of LIPE promoter A in cells transfected with the luciferase reporter vector. Overexpression of steroidogenic factor-1 (SF-1) increased LIPE promoter activity, while transient silencing of SF-1 expression with specific siRNAs abolished forskolin-stimulated LIPE transcription. It is concluded that ACTH via the PKA pathway stimulates expression of SF-1, which activates transcription of LIPE presumably by interaction with putative binding sequences within promoter A. A novel mechanism contributing to the long-term effect of ACTH on adrenal steroidogenesis is proposed: ACTH stimulates transcription of SF-1, which interacts with the putative SF-1-binding sequences within the promoter and activates LIPE transcription. An increased level of HSL results in an enhanced supply of cholesterol required for steroid hormone synthesis.

show abstract

Inhibition of hormone-sensitive lipase gene expression by cAMP and phorbol esters in 3T3-F442A and BFC-1 adipocytes

Cited by 38 publications

References 44 publications

Changes in lipolysis and hormone-sensitive lipase expression caused by procyanidins in 3T3-L1 adipocytes

Changes in lipolysis and hormone-sensitive lipase expression caused by procyanidins in 3T3-L1 adipocytes

Transcriptional Regulation of Adipocyte Hormone-Sensitive Lipase by Glucose

Transcription of LIPE gene encoding hormone-sensitive lipase/cholesteryl esterase is regulated by SF-1 in human adrenocortical cells: involvement of protein kinase A signal transduction pathway

Contact Info

Product

Resources

About