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The β3-adrenergic receptor is dispensable for browning of adipose tissues
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.ORCID-id: 0000-0001-8044-5410
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
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2017 (Engelska)Ingår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 312, nr 6, s. E508-E518Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Brown and brite/beige adipocytes are attractive therapeutic targets to treat metabolic diseases. To maximally utilize their functional potential, further understanding is required about their identities and their functional differences. Recent studies with β3-adrenergic receptor knockout mice reported that brite/beige adipocytes, but not classical brown adipocytes, require the β3-adrenergic receptor for cold-induced transcriptional activation of thermogenic genes. We aimed to further characterize this requirement of the β3-adrenergic receptor as a functional distinction between classical brown and brite/beige adipocytes. However, when comparing wild-type and β3-adrenergic receptor knockout mice, we observed no differences in cold-induced thermogenic gene expression (Ucp1, Pgc1a, Dio2 and Cidea) in brown or white (brite/beige) adipose tissues. Irrespective of the duration of the cold exposure or the sex of the mice, we observed no effect of the absence of the β3-adrenergic receptor. Experiments with the β3-adrenergic receptor agonist CL-316,243 verified the functional absence of β3-adrenergic signaling in these knockout mice. The β3-adrenergic receptor knockout model in the present study was maintained on a FVB/N background, whereas earlier reports used C57BL/6 and 129Sv mice. Thus, our data imply background-dependent differences in adrenergic signaling mechanisms in response to cold exposure. Nonetheless, the present data indicate that the β3-adrenergic receptor is dispensable for cold-induced transcriptional activation in both classical brown and, as opposed to earlier studies, brite/beige cells. This should be taken into account in the increasing number of studies on the induction of browning and their extrapolation to human physiology.

Ort, förlag, år, upplaga, sidor
2017. Vol. 312, nr 6, s. E508-E518
Nyckelord [en]
β3-adrenergic receptor, adipose browning, brown adipocytes, brite/beige adipocytes, UCP
Nationell ämneskategori
Cellbiologi
Forskningsämne
fysiologi
Identifikatorer
URN: urn:nbn:se:su:diva-140882DOI: 10.1152/ajpendo.00437.2016ISI: 000404391300005PubMedID: 28223294OAI: oai:DiVA.org:su-140882DiVA, id: diva2:1083354
Tillgänglig från: 2017-03-21 Skapad: 2017-03-21 Senast uppdaterad: 2022-02-28Bibliografiskt granskad
Ingår i avhandling
1. Who is Who in the Adipose Organ: A look at the Heterogeneity of Adipocyte Biology
Öppna denna publikation i ny flik eller fönster >>Who is Who in the Adipose Organ: A look at the Heterogeneity of Adipocyte Biology
2017 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
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.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2017. s. 92
Nyckelord
Adipose tissue, Adipocyte, Brown, White, Brite/Beige, Physiology
Nationell ämneskategori
Fysiologi
Forskningsämne
fysiologi
Identifikatorer
urn:nbn:se:su:diva-140884 (URN)978-91-7649-742-5 (ISBN)978-91-7649-743-2 (ISBN)
Disputation
2017-04-28, Vivi Täckholmsalen (Q211), NPQ-huset, Svante Arrheniusväg 20, Stockholm, 10:00 (Engelska)
Opponent
Handledare
Anmärkning

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.

Tillgänglig från: 2017-04-05 Skapad: 2017-03-21 Senast uppdaterad: 2022-02-28Bibliografiskt granskad

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de Jong, Jasper M. A.Boulet, NathalieCannon, BarbaraNedergaard, JanPetrovic, Natasa

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de Jong, Jasper M. A.Boulet, NathalieCannon, BarbaraNedergaard, JanPetrovic, Natasa
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Institutionen för molekylär biovetenskap, Wenner-Grens institut
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American Journal of Physiology. Endocrinology and Metabolism
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