Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Role of caveolin-1 in brown adipose tissue
Stockholm University, Faculty of Science, The Wenner-Gren Institute .
2010 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Caveolae are 50-100 nm invaginations in the plasma membrane. Caveolae and the protein caveolin-1 (Cav1) have been shown to be important in many signaling pathways in different cell types; however, in some cell types caveolae and Cav1 do not seem to affect the investigated signaling pathways. In my thesis, I have investigated the role of caveolin-1 (Cav1) in metabolism and b3-adrenergic, LPA-, EGF- and PDGF-receptor signaling in brown adipocytes.

Brown adipose tissue is responsible for nonshivering thermogenesis. Recent studies have shown that not only infants but also adult man can have brown adipose tissue and that the presence is negatively correlated with both obesity and age. By understanding how signaling for proliferation and differentiation in brown adipocytes is regulated, it could be possible in the future to activate brown adipose tissue to combat obesity and the metabolic syndrome.

In brown adipocytes, both epidermal growth factor (EGF) and platelet-derived growth factor (PDGF) were able to induce proliferation, which was dependent on Erk1/2 activation. However, EGF and PDGF utilized different pathways to activate Erk1/2, with EGF signaling partially occurring via a Src-pathway (not involving PI3K/PKC) and PDGF via a PI3K/PKC/Src-pathway. Furthermore, LPA receptors were able to activate Erk1/2 via two pathways, one Gi/PKC/Src-pathway and one PI3K-pathway. For these receptors, Cav1-ablation did not affect the agonist-induced Erk1/2 activation. Cav1 was, however, required for proper b3-adrenergic receptor (b3-AR) signaling to cAMP and for adenylyl cyclase activity.

In Cav1-ablated mice, the adrenergic receptors are desensitized. However, this desensitization could be overcome physiologically, and the Cav1-ablated mice were therefore able to survive in prolonged cold by nonshivering thermogenesis.

In conclusion, ablation of Cav1 affected certain signaling pathways in brown adipocytes, while other pathways were not affected or could be physiologically rescued.

Place, publisher, year, edition, pages
Stockholm: The Wenner-Gren Institute, Stockholm University , 2010. , 110 p.
Keyword [en]
caveolin, brown adipose tissue, metabolism, signaling
National Category
Physiology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:su:diva-37125ISBN: 978-91-7447-005-5 (print)OAI: oai:DiVA.org:su-37125DiVA: diva2:293043
Public defence
2010-03-12, Hörsal 107, Frescati Backe, Svante Arrhenius väg 21 A, Stockholm, 10:00 (English)
Opponent
Supervisors
Note
At the time of the doctoral defense, the following papers were unpublished and had a status as follows: Paper 1: Manuscript. Paper 3: Manuscript. Paper 4: Manuscript.Available from: 2010-02-18 Created: 2010-02-10 Last updated: 2010-02-16Bibliographically approved
List of papers
1. Caveolin-1-ablated mice survive cold by nonshivering thermogenesis, despite desensitized adrenergic receptors
Open this publication in new window or tab >>Caveolin-1-ablated mice survive cold by nonshivering thermogenesis, despite desensitized adrenergic receptors
Show others...
(English)Manuscript (preprint) (Other academic)
Identifiers
urn:nbn:se:su:diva-37121 (URN)
Available from: 2010-02-10 Created: 2010-02-10 Last updated: 2010-02-11Bibliographically approved
2. Differential signalling pathways for EGF versus PDGF activation of Erk1/2 MAP kinase and cell proliferation in brown pre-adipocytes
Open this publication in new window or tab >>Differential signalling pathways for EGF versus PDGF activation of Erk1/2 MAP kinase and cell proliferation in brown pre-adipocytes
2008 (English)In: Experimental Cell Research, ISSN 0014-4827, Vol. 314, no 19, 3581-3592 p.Article in journal (Refereed) Published
Identifiers
urn:nbn:se:su:diva-15807 (URN)10.1016/j.yexcr.2008.09.007 (DOI)000261457200014 ()18838072 (PubMedID)
Available from: 2008-12-10 Created: 2008-12-10 Last updated: 2010-02-11Bibliographically approved
3. Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes
Open this publication in new window or tab >>Non-transactivational, dual pathways for LPA-induced Erk1/2 activation in primary cultures of brown pre-adipocytes
Show others...
2010 (English)In: Experimental Cell Research, ISSN 0014-4827, E-ISSN 1090-2422, Vol. 316, no 16, 2664-75 p.Article in journal (Refereed) Published
Abstract [en]

In many cell types, G-protein-coupled receptor (GPCR)-induced Erk1/2 MAP kinase activation is mediated via receptor tyrosine kinase (RTK) transactivation, in particular via the epidermal growth factor (EGF) receptor. Lysophosphatidic acid (LPA), acting via GPCRs, is a mitogen and MAP kinase activator in many systems, and LPA can regulate adipocyte proliferation. The mechanism by which LPA activates the Erk1/2 MAP kinase is generally accepted to be via EGF receptor transactivation. In primary cultures of brown pre-adipocytes, EGF can induce Erk1/2 activation, which is obligatory and determinant for EGF-induced proliferation of these cells. Therefore, we have here examined whether LPA, via EGF transactivation, can activate Erk1/2 in brown pre-adipocytes. We found that LPA could induce Erk1/2 activation. However, the LPA-induced Erk1/2 activation was independent of transactivation of EGF receptors (or PDGF receptors) in these cells (whereas in transformed HIB-1B brown adipocytes, the LPA-induced Erk1/2 activation indeed proceeded via EGF receptor transactivation). In the brown pre-adipocytes, LPA instead induced Erk1/2 activation via two distinct non-transactivational pathways, one G(i)-protein dependent, involving PKC and Src activation, the other, a PTX-insensitive pathway, involving PI3K (but not Akt) activation. Earlier studies showing LPA-induced Erk1/2 activation being fully dependent on RTK transactivation have all been performed in cell lines and transfected cells. The present study implies that in non-transformed systems, RTK transactivation may not be involved in the mediation of GPCR-induced Erk1/2 MAP kinase activation

Keyword
Lysophosphatidic acid, Transactivation, Brown adipocytes, Erk1/2, EGF receptor, PI3K
National Category
Other Biological Topics
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-37122 (URN)10.1016/j.yexcr.2010.05.029 (DOI)000281305800013 ()20576526 (PubMedID)
Available from: 2010-02-10 Created: 2010-02-10 Last updated: 2013-03-22Bibliographically approved
4. Differential involvement of caveolin-1 in brown adipocyte signaling: impaired b3-adrenergic but unaffected LPA, PDGF and EGF receptor
Open this publication in new window or tab >>Differential involvement of caveolin-1 in brown adipocyte signaling: impaired b3-adrenergic but unaffected LPA, PDGF and EGF receptor
(English)Manuscript (preprint) (Other academic)
Identifiers
urn:nbn:se:su:diva-37124 (URN)
Available from: 2010-02-10 Created: 2010-02-10 Last updated: 2010-02-11Bibliographically approved

Open Access in DiVA

fulltext(1625 kB)761 downloads
File information
File name FULLTEXT01.pdfFile size 1625 kBChecksum SHA-512
f4a3fa5ed7251a0c41776eeb9aa6fa08ee910c4c753e90af7e786b6226b3d70ff7820d6c6a62dc397d1d53186b213f204ab5466a4a1b64f3842a2b89ad39ed86
Type fulltextMimetype application/pdf

Search in DiVA

By author/editor
Mattsson, Charlotte L.
By organisation
The Wenner-Gren Institute
Physiology

Search outside of DiVA

GoogleGoogle Scholar
Total: 761 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

isbn
urn-nbn

Altmetric score

isbn
urn-nbn
Total: 445 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf