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A stringent validation of mouse adipose tissue identity markers
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
Number of Authors: 4
2015 (English)In: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 308, no 12, E1085-E1105 p.Article in journal (Refereed) Published
Abstract [en]

The nature of brown adipose tissue in humans is presently debated: whether it is classical brown or of brite/beige nature. The dissimilar developmental origins and proposed distinct functions of the brown and brite/beige tissues make it essential to ascertain the identity of human depots with the perspective of recruiting and activating them for the treatment of obesity and type 2 diabetes. For identification of the tissues, a number of marker genes have been proposed, but the validity of the markers has not been well documented. We used established brown (interscapular), brite (inguinal), and white (epididymal) mouse adipose tissues and corresponding primary cell cultures as validators and examined the informative value of a series of suggested markers earlier used in the discussion considering the nature of human brown adipose tissue. Most of these markers unexpectedly turned out to be noninformative concerning tissue classification (Car4, Cited1, Ebf3, Eva1, Fbxo31, Fgf21, Lhx8, Hoxc8, and Hoxc9). Only Zic1 (brown), Cd137, Epsti1, Tbx1, Tmem26 (brite), and Tcf21 (white) proved to be informative in these three tissues. However, the expression of the brite markers was not maintained in cell culture. In a more extensive set of adipose depots, these validated markers provide new information about depot identity. Principal component analysis supported our single-gene conclusions. Furthermore, Zic1, Hoxc8, Hoxc9, and Tcf21 displayed anteroposterior expression patterns, indicating a relationship between anatomic localization and adipose tissue identity (and possibly function). Together, the observed expression patterns of these validated marker genes necessitates reconsideration of adipose depot identity in mice and humans.

Place, publisher, year, edition, pages
2015. Vol. 308, no 12, E1085-E1105 p.
Keyword [en]
adipose tissue, brown, brite, beige, white
National Category
Cell Biology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:su:diva-118962DOI: 10.1152/ajpendo.00023.2015ISI: 000356259500006OAI: oai:DiVA.org:su-118962DiVA: diva2:842727
Available from: 2015-07-22 Created: 2015-07-21 Last updated: 2017-12-04Bibliographically approved
In thesis
1. Who is Who in the Adipose Organ: A look at the Heterogeneity of Adipocyte Biology
Open this publication in new window or tab >>Who is Who in the Adipose Organ: A look at the Heterogeneity of Adipocyte Biology
2017 (English)Doctoral thesis, comprehensive summary (Other academic)
Abstract [en]

The increasing prevalence of obesity and related health complications, such as type 2 diabetes, cardiovascular disease and cancer, demands thorough investigation of the underlying processes. One of the key tissues investigated in this context is adipose tissue. It is becoming increasingly clear that adipose tissue is a very dynamic and heterogenic organ. This thesis provides an overview of various aspects of adipose biology that illustrate its heterogenic nature and describes my own scientific contributions to this field.

We typically distinguish between thermogenic, energy-expending brown adipocytes and energy-storing white adipocytes that are located in anatomically distinct adipose depots. In addition, brite (or beige) adipocytes are functionally thermogenic, but are located among white adipocytes.

Related to functional variation, adipocytes and adipose tissues display a wide range of morphological appearances. An additional property that illustrates the heterogeneity among adipose cells and depots is the variation of cellular responses to physiological cues, such as changes in diet or environmental temperature. Furthermore, the developmental origins of various adipose types display great heterogeneity, which may explain some of the functional and dynamic differences that are observed.

In line with the complexity of developmental origins, molecular markers that were initially proposed to distinguish between brown, brite/beige and white adipose subtypes have added to the notion that the composition of the adipose organ is much more complex than has long been appreciated.

My own work has contributed to the enhancement of our understanding of the heterogeneity of adipose subtypes. In particular, my findings related to marker gene expression patterns have led to increased appreciation of the complex nature of adipose gene expression patterns and the complications of translating results obtained in mice to humans. Some of my other contributions have increased the understanding of the differences and similarities in thermogenic adipose tissue functionality and dynamics. With cell culture studies, I have revealed new characteristics of pre-adipose cells from various depots that further add to the appreciation of the adipose heterogeneity.

Overall, this thesis provides an overview of important characteristics of the adipose organ, illustrating its heterogenic nature. Realization of this heterogeneity is of importance in order to properly study the adipose organ to ultimately understand how the adipose organ can be therapeutically targeted to effectively treat adipose-related diseases.

Place, publisher, year, edition, pages
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2017. 92 p.
Keyword
Adipose tissue, Adipocyte, Brown, White, Brite/Beige, Physiology
National Category
Physiology
Research subject
Physiology
Identifiers
urn:nbn:se:su:diva-140884 (URN)978-91-7649-742-5 (ISBN)978-91-7649-743-2 (ISBN)
Public defence
2017-04-28, Vivi Täckholmsalen (Q211), NPQ-huset, Svante Arrheniusväg 20, 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 3: Manuscript. Paper 7: Manuscript. Paper 8: Manuscript.

Available from: 2017-04-05 Created: 2017-03-21 Last updated: 2017-04-03Bibliographically approved

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