ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation
ApoA-I, the main protein component of HDL, is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high-fat-fed mice treated with Milano displayed a rapid weigh...
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doaj-0aa81832a4b14fbda3c35032f37a58122021-04-29T04:34:25ZengElsevierJournal of Lipid Research0022-22752015-12-01561222482259ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activationMaria Lindahl0Jitka Petrlova1Jonathan Dalla-Riva2Sebastian Wasserstrom3Catarina Rippe4Joan Domingo-Espin5Dorota Kotowska6Ewa Krupinska7Christine Berggreen8Helena A. Jones9Karl Swärd10Jens O. Lagerstedt11Olga Göransson12Karin G. Stenkula13Medical Protein Science, Lund University, 221 84 Lund, Sweden; Glucose Transport and Protein Trafficking, Lund University, 221 84 Lund, SwedenMedical Protein Science, Lund University, 221 84 Lund, SwedenMedical Protein Science, Lund University, 221 84 Lund, SwedenGlucose Transport and Protein Trafficking, Lund University, 221 84 Lund, SwedenCellular Biomechanics, Lund University, 221 84 Lund, SwedenMedical Protein Science, Lund University, 221 84 Lund, SwedenGlucose Transport and Protein Trafficking, Lund University, 221 84 Lund, SwedenMedical Protein Science, Lund University, 221 84 Lund, SwedenProtein Phosphorylation, Lund University, 221 84 Lund, SwedenMolecular Endocrinology, Department of Experimental Medical Science, Biomedical Center, Lund University, 221 84 Lund, SwedenCellular Biomechanics, Lund University, 221 84 Lund, SwedenMedical Protein Science, Lund University, 221 84 Lund, SwedenProtein Phosphorylation, Lund University, 221 84 Lund, SwedenGlucose Transport and Protein Trafficking, Lund University, 221 84 Lund, Sweden; To whom correspondence should be addressed.ApoA-I, the main protein component of HDL, is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high-fat-fed mice treated with Milano displayed a rapid weight loss greater than ApoA-I WT treated mice, and a significantly reduced adipose tissue mass, without an inflammatory response. Further, lipolysis in adipose cells isolated from mice treated with either WT or Milano was increased. In primary rat adipose cells, Milano stimulated cholesterol efflux and increased glycerol release, independently of β-adrenergic stimulation and phosphorylation of hormone sensitive lipase (Ser563) and perilipin (Ser522). Stimulation with Milano had a significantly greater effect on glycerol release compared with WT but similar effect on cholesterol efflux. Pharmacological inhibition or siRNA silencing of ABCA1 did not diminish Milano-stimulated lipolysis, although binding to the cell surface was decreased, as analyzed by fluorescence microscopy. Interestingly, methyl-β-cyclodextrin, a well-described cholesterol acceptor, dose-dependently stimulated lipolysis. Together, these results suggest that decreased fat mass and increased lipolysis following Milano treatment in vivo is partly explained by a novel mechanism at the adipose cell level comprising stimulation of lipolysis independently of the canonical cAMP/protein kinase A signaling pathway.. J. Lipid Res. 2015. 56: 2248–2259.http://www.sciencedirect.com/science/article/pii/S0022227520309457adipose tissueapolipoprotein A-Icholesteroldiabetesobesityadenosine 3′,5′-cyclic monophosphate |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Maria Lindahl Jitka Petrlova Jonathan Dalla-Riva Sebastian Wasserstrom Catarina Rippe Joan Domingo-Espin Dorota Kotowska Ewa Krupinska Christine Berggreen Helena A. Jones Karl Swärd Jens O. Lagerstedt Olga Göransson Karin G. Stenkula |
spellingShingle |
Maria Lindahl Jitka Petrlova Jonathan Dalla-Riva Sebastian Wasserstrom Catarina Rippe Joan Domingo-Espin Dorota Kotowska Ewa Krupinska Christine Berggreen Helena A. Jones Karl Swärd Jens O. Lagerstedt Olga Göransson Karin G. Stenkula ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation Journal of Lipid Research adipose tissue apolipoprotein A-I cholesterol diabetes obesity adenosine 3′,5′-cyclic monophosphate |
author_facet |
Maria Lindahl Jitka Petrlova Jonathan Dalla-Riva Sebastian Wasserstrom Catarina Rippe Joan Domingo-Espin Dorota Kotowska Ewa Krupinska Christine Berggreen Helena A. Jones Karl Swärd Jens O. Lagerstedt Olga Göransson Karin G. Stenkula |
author_sort |
Maria Lindahl |
title |
ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation |
title_short |
ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation |
title_full |
ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation |
title_fullStr |
ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation |
title_full_unstemmed |
ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation |
title_sort |
apoa-i milano stimulates lipolysis in adipose cells independently of camp/pka activation |
publisher |
Elsevier |
series |
Journal of Lipid Research |
issn |
0022-2275 |
publishDate |
2015-12-01 |
description |
ApoA-I, the main protein component of HDL, is suggested to be involved in metabolic homeostasis. We examined the effects of Milano, a naturally occurring ApoA-I variant, about which little mechanistic information is available. Remarkably, high-fat-fed mice treated with Milano displayed a rapid weight loss greater than ApoA-I WT treated mice, and a significantly reduced adipose tissue mass, without an inflammatory response. Further, lipolysis in adipose cells isolated from mice treated with either WT or Milano was increased. In primary rat adipose cells, Milano stimulated cholesterol efflux and increased glycerol release, independently of β-adrenergic stimulation and phosphorylation of hormone sensitive lipase (Ser563) and perilipin (Ser522). Stimulation with Milano had a significantly greater effect on glycerol release compared with WT but similar effect on cholesterol efflux. Pharmacological inhibition or siRNA silencing of ABCA1 did not diminish Milano-stimulated lipolysis, although binding to the cell surface was decreased, as analyzed by fluorescence microscopy. Interestingly, methyl-β-cyclodextrin, a well-described cholesterol acceptor, dose-dependently stimulated lipolysis. Together, these results suggest that decreased fat mass and increased lipolysis following Milano treatment in vivo is partly explained by a novel mechanism at the adipose cell level comprising stimulation of lipolysis independently of the canonical cAMP/protein kinase A signaling pathway.. J. Lipid Res. 2015. 56: 2248–2259. |
topic |
adipose tissue apolipoprotein A-I cholesterol diabetes obesity adenosine 3′,5′-cyclic monophosphate |
url |
http://www.sciencedirect.com/science/article/pii/S0022227520309457 |
work_keys_str_mv |
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