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ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation.

Authors
  • Lindahl, Maria1
  • Petrlova, Jitka2
  • Dalla-Riva, Jonathan2
  • Wasserstrom, Sebastian3
  • Rippe, Catarina4
  • Domingo-Espin, Joan2
  • Kotowska, Dorota3
  • Krupinska, Ewa2
  • Berggreen, Christine5
  • Jones, Helena A6
  • Swärd, Karl4
  • Lagerstedt, Jens O2
  • Göransson, Olga5
  • Stenkula, Karin G7
  • 1 Medical Protein Science, Lund University, 221 84 Lund, Sweden Glucose Transport and Protein Trafficking, Lund University, 221 84 Lund, Sweden. , (Sweden)
  • 2 Medical Protein Science, Lund University, 221 84 Lund, Sweden. , (Sweden)
  • 3 Glucose Transport and Protein Trafficking, Lund University, 221 84 Lund, Sweden. , (Sweden)
  • 4 Cellular Biomechanics, Lund University, 221 84 Lund, Sweden. , (Sweden)
  • 5 Protein Phosphorylation, Lund University, 221 84 Lund, Sweden. , (Sweden)
  • 6 Molecular Endocrinology, Department of Experimental Medical Science, Biomedical Center, Lund University, 221 84 Lund, Sweden. , (Sweden)
  • 7 Glucose Transport and Protein Trafficking, Lund University, 221 84 Lund, Sweden [email protected] , (Sweden)
Type
Published Article
Journal
The Journal of Lipid Research
Publisher
"American Society for Biochemistry and Molecular Biology, Journal of Lipid Research"
Publication Date
Dec 01, 2015
Volume
56
Issue
12
Pages
2248–2259
Identifiers
DOI: 10.1194/jlr.M054767
PMID: 26504176
Source
Medline
Keywords
License
Unknown

Abstract

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.

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