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The secretome of brown adipose tissue
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
2014 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

Brown adipose tissue has long been known for its heat-producing capacity, but less is known about its possible effects as a secretory organ. This thesis summarizes information about presently known factors secreted from brown adipose tissue and about their actions. We were able to add factors to the list by the use of a signal-sequence trap method. Results from the signal-sequence trap generated a list of suggested brown adipocyte secreted proteins; gene expression of these proteins was then further studied with microarray technique.

One of the genes further analyzed was the adipokine chemerin. Gene expression of chemerin in brown adipose tissue was decreased in cold acclimation but increased with a high-caloric diet. This indicates that factors other than norepinephrine influence chemerin gene expression. The effects on chemerin gene expression were not be reflected in serum levels; therefore, chemerin secreted from brown adipose tissue is ascribed an autocrine/paracrine role.

Signal-sequence trap and microarray studies suggested adrenomedullin, collagen type 3 a1, lipocalin 2 and Niemann Pick type C2 to be highly secreted from brown adipocytes. Gene expression of these factors was examined in vivo and in vitro. Our studies showed that both cold acclimation and high-caloric diet have an effect on gene expression of these factors. However, there was no effect on gene expression of chemerin and collagen type 3 a1 in norepinephrine-treated brown adipocyte cell cultures. This suggests that effects on gene expression of the examined possible brown adipocyte secreted proteins are not solely controlled by norepinephrine.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University , 2014. , 101 p.
National Category
Biochemistry and Molecular Biology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:su:diva-102934ISBN: 978-91-7447-903-4 (print)OAI: oai:DiVA.org:su-102934DiVA: diva2:714076
Public defence
2014-05-28, Lecture hall E306, Arrheniuslaboratorierna, Svante Arrhenius väg 20 C, Stockholm, 10:00 (English)
Opponent
Supervisors
Note

At the time of doctoral defence the following papers were unpublished and had a status as follows: Paper 1: Manuscript; Paper 3: Manuscript; Paper  4: Manuscript; Paper 5: Manuscript

Available from: 2014-05-06 Created: 2014-04-25 Last updated: 2014-04-28Bibliographically approved
List of papers
1. A partial secretome of brown adipose tissue
Open this publication in new window or tab >>A partial secretome of brown adipose tissue
(English)Manuscript (preprint) (Other academic)
Abstract [en]

To identify brown adipocyte secreted proteins a signal-sequence trap method was used. All genes identified were cloned and studied with microarray technique.

The aim of this study was to evaluate how these genes were influenced under different physiological conditions, both

in vivo and in vitro. Microarray studies were performed comparing primary brown adipocytes stimulated with norepinephrine to non-stimulated, and primary brown adipocytes compared to primary white adipocytes. In vivo studies were performed to evaluate physiological effects on gene expression in brown adipose tissue. Male NMRI mice were placed in cold or at thermoneutrality for 3 weeks and compared. Mice kept at room temperature were exposed to cafeteria diet for three weeks compared to regular diet.

Results show that norepinephrine had effects on the expression of these potentially secreted genes. However, gene expression from physiological studies

in vivo that could be expected to show similar expression patterns as norepinephrine-treated brown adipocytes did not do so. This indicates that other factors than norepinephrine can regulate gene expression of possible brown adipose tissue-secreted factors.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-102928 (URN)
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2014-04-25
2. Recruited vs. nonrecruited molecular signatures of brown, “brite,” and white adipose tissues
Open this publication in new window or tab >>Recruited vs. nonrecruited molecular signatures of brown, “brite,” and white adipose tissues
Show others...
2011 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 302, no 1, E19-E31 p.Article in journal (Refereed) Published
Abstract [en]

Mainly from cell culture studies, a series of genes have been identified that have been suggested to be characteristic of different types of adipocytes. Here we have examined gene expression patterns in nine defined adipose depots: interscapular BAT, cervical BAT, axillary BAT, mediastinic BAT, cardiac WAT, inguinal WAT, retroperitoneal WAT, mesenteric WAT and epididymal WAT. We found that each depot displayed a distinct gene expression fingerprint, but that three major types of depots were identifiable: the brown, the brite and the white. Although differences in gene expression pattern were generally quantitative, some gene markers showed, even in-vivo, remarkable depot specificities: Zic1 for the classical brown adipose tissue depots, Hoxc9 for the brite depots, Hoxc8 for the brite and white in contrast to the brown, and Tcf21 for the white depots. The significance of these gene expression patterns both for understanding the developmental background of the depots and as possible master regulators is discussed.

Keyword
uncoupling protein 1, pr domain containing 16, sirtuins, short stature homeobox, carbonic anhydrase 3
National Category
Physiology
Identifiers
urn:nbn:se:su:diva-65632 (URN)10.1152/ajpendo.00249.2011 (DOI)000298377600003 ()21828341 (PubMedID)
Available from: 2011-12-13 Created: 2011-12-13 Last updated: 2017-12-08Bibliographically approved
3. Contrasting effects of cold acclimation versus obesogenic diets onchemerin gene expression in brown and brite adipose tissues
Open this publication in new window or tab >>Contrasting effects of cold acclimation versus obesogenic diets onchemerin gene expression in brown and brite adipose tissues
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Based on results from a signal sequence trap, we investigated chemerin gene expression in brown adipose tissue. Male NMRI mice were exposed to 30, 22 or 4 °C for 3 weeks, or were fed control (chow) diet, cafeteria diet or high-fat diet at thermoneutrality for the same time. In brown adipose tissue, cold acclimation strongly diminished chemerin gene expression, whereas obesogenic diets augmented expression. Qualitatively, changes in expression were paralleled in brite/beige adipose tissues (e.g. inguinal), whereas white adipose tissue (epididymal) did not react to these cues. Changes in tissue expression were not paralleled by alterations in plasma levels. The cellular regulation was not congruent with a sympathetic/adrenergic control of expression. The data are discussed in relation to suggested endocrine, paracrine and autocrine effects of this adipokine.

National Category
Natural Sciences Biochemistry and Molecular Biology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-102923 (URN)
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2014-04-25
4. Physiological effects on gene expression of some brown adipose tissue secreted factors
Open this publication in new window or tab >>Physiological effects on gene expression of some brown adipose tissue secreted factors
(English)Manuscript (preprint) (Other academic)
Abstract [en]

Background: To investigate the role of brown adipose tissue as a secretory organ, a signal-sequence trap and microarray study were performed. Results indicated that adrenomedullin, collagen type 3 a1, lipocalin 2 and Niemann Pick type C 2 could be possible brown adipocyte-secreted proteins.

Method: To investigate the physiological regulation of the gene expression of the adrenomedullin, collagen 3 a1, lipocalin 2 and Niemann Pick type C2 in brown adipose tissue, the following study was performed. Mice were exposed to cold or different high-caloric diets (high-fat diet and cafeteria diet) for three weeks and qPCR studies were performed of the genes of interest.

Results & Conclusion: The study indicates that cold acclimation significantly suppressed gene expression of adrenomedullin, collagen type 3a and lipocalin 2 (P < 0.05). There was also an effect of the different diets but the results were not cohesive between the two high-caloric diets. However, none of the expression patterns between the cold-acclimated mice or the diet studies overlapped, suggesting that norepinephrine is not the key regulator of the gene expression of any of the investigated genes

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-102932 (URN)
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2014-04-25
5. Effects of differentiation on gene expression of certain brown adipocyte-secreted factors
Open this publication in new window or tab >>Effects of differentiation on gene expression of certain brown adipocyte-secreted factors
(English)Manuscript (preprint) (Other academic)
Abstract [en]

The possibility that brown adipose tissue can secrete factors to affect overall metabolism is a subject that attracts attention. Previous studies from our laboratory suggest that chemerin and collagen type III a1 (Col3a1) could be interesting factors secreted from brown adipose tissue.

To evaluate chemerin and Col3a1 gene expression regulation, primary brown adipocyte cultures were stimulated with norepinephrine at different stages of differentiation. The present study shows that there was an effect of differentiation on gene expression of these factors but there was no effect of norepinephrine treatment.

There has been a suggestion that different adenylate cyclases are responsible for regulating gene expression in brown adipocytes. However, neither differentiation nor norepinephrine treatment affected adenylate cyclase gene expression dramatically.

The results suggest that norepinephrine is not the main regulator of gene expression of either of the two possible brown adipocyte-secreted factors, chemerin and Col3a1. Surprisingly, norepinephrine had no major effect on adenylate cyclase expression at any stage of differentiation.

National Category
Biochemistry and Molecular Biology
Identifiers
urn:nbn:se:su:diva-102933 (URN)
Available from: 2014-04-25 Created: 2014-04-25 Last updated: 2014-04-25

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