ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation.
(2015) In Journal of Lipid Research 56(12). p.2248-2259- Abstract
- ApoA-I, the main protein component of high-density lipoprotein (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... (More)
- ApoA-I, the main protein component of high-density lipoprotein (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 ABCA-1 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/PKA signaling pathway. (Less)
Please use this url to cite or link to this publication:
https://lup.lub.lu.se/record/8148266
- author
- organization
-
- Glucose Transport and Protein Trafficking (research group)
- Dermatology and Venereology (Lund)
- Medical Protein Science (research group)
- Cellular Biomechanics (research group)
- Molecular Cell Biology
- Protein Phosphorylation (research group)
- Molecular Endocrinology (research group)
- EXODIAB: Excellence of Diabetes Research in Sweden
- publishing date
- 2015
- type
- Contribution to journal
- publication status
- published
- subject
- in
- Journal of Lipid Research
- volume
- 56
- issue
- 12
- pages
- 2248 - 2259
- publisher
- American Society for Biochemistry and Molecular Biology
- external identifiers
-
- pmid:26504176
- wos:000365843800003
- scopus:84948949600
- pmid:26504176
- ISSN
- 1539-7262
- DOI
- 10.1194/jlr.M054767
- language
- English
- LU publication?
- yes
- id
- 04e6bf9a-84de-4a78-a97a-749f62c140a0 (old id 8148266)
- alternative location
- http://www.ncbi.nlm.nih.gov/pubmed/26504176?dopt=Abstract
- date added to LUP
- 2016-04-01 10:24:35
- date last changed
- 2024-02-21 15:58:58
@article{04e6bf9a-84de-4a78-a97a-749f62c140a0, abstract = {{ApoA-I, the main protein component of high-density lipoprotein (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 ABCA-1 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/PKA signaling pathway.}}, author = {{Lindahl, Maria and Petrlova, Jitka and Dalla-Riva, Jonathan and Wasserstrom, Sebastian and Rippe, Catarina and Domingo-Espin, Joan and Kotowska, Dorota and Krupinska, Ewa and Berggreen, Christine and Jones, Helena and Swärd, Karl and Lagerstedt, Jens and Göransson, Olga and Stenkula, Karin}}, issn = {{1539-7262}}, language = {{eng}}, number = {{12}}, pages = {{2248--2259}}, publisher = {{American Society for Biochemistry and Molecular Biology}}, series = {{Journal of Lipid Research}}, title = {{ApoA-I Milano stimulates lipolysis in adipose cells independently of cAMP/PKA activation.}}, url = {{http://dx.doi.org/10.1194/jlr.M054767}}, doi = {{10.1194/jlr.M054767}}, volume = {{56}}, year = {{2015}}, }