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UCP1 in Brite/Beige Adipose Tissue Mitochondria Is Functionally Thermogenic
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.
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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2013 (English)In: Cell reports, ISSN 2211-1247, E-ISSN 2211-1247, Vol. 5, no 5, 1196-1203 p.Article in journal (Refereed) Published
Abstract [en]

The phenomenon of white fat browning, in which certain white adipose tissue depots significantly increase gene expression for the uncoupling protein UCP1 and thus supposedly acquire thermogenic, fat-burning properties, has attracted considerable attention. Because the mRNA increases are from very low initial levels, the metabolic relevance of the change is unclear: is the UCP1 protein thermogenically competent in these brite/beige-fat mitochondria? We found that, in mitochondria isolated from the inguinal white adipose depot of cold-acclimated mice, UCP1 protein levels almost reached those in brown-fat mitochondria. The UCP1 was thermogenically functional, in that these mitochondria exhibited UCP1-dependent thermogenesis with lipid or carbohydrate substrates with canonical guanosine diphosphate (GDP) sensitivity and loss of thermogenesis in UCP1 knockout (KO) mice. Obesogenic mouse strains had a lower thermogenic potential than obesity-resistant strains. The thermogenic density (UCP1-dependent oxygen consumption per g tissue) of inguinal white adipose tissue was maximally one-fifth of interscapular brown adipose tissue, and the total quantitative contribution of all inguinal mitochondria was maximally one-third of all interscapular brown-fat mitochondria, indicating that the classical brown adipose tissue depots would still predominate in thermogenesis.

Place, publisher, year, edition, pages
2013. Vol. 5, no 5, 1196-1203 p.
National Category
Cell Biology
Research subject
Physiology
Identifiers
URN: urn:nbn:se:su:diva-99135DOI: 10.1016/j.celrep.2013.10.044ISI: 000328266400005OAI: oai:DiVA.org:su-99135DiVA: diva2:686764
Note

AuthorCount:6;

Available from: 2014-01-13 Created: 2014-01-12 Last updated: 2017-12-06Bibliographically 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)
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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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Shabalina, Irina G.Petrovic, Natasade Jong, Jasper M. A.Kalinovich, AnastasiaCannon, BarbaraNedergaard, Jan
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