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Adrenergically-stimulated blood flow in brown adipose tissue is not dependent on thermogenesis: Regulation of brown adipose tissue blood flow
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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2015 (Engelska)Ingår i: American Journal of Physiology. Endocrinology and Metabolism, ISSN 0193-1849, E-ISSN 1522-1555, Vol. 308, nr 9, s. E822-E829Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

Brown adipose tissue (BAT) thermogenesis relies on blood flow to be supplied with nutrients and oxygen, and for the distribution of the generated heat to the rest of the body. It is therefore fundamental to understand the mechanisms by which blood flow is regulated and its relation to thermogenesis. Here we present high-resolution laser-Doppler imaging (HR-LDR) as a novel method for noninvasive, in vivo measurement of BAT blood flow in mice. Using HR-LDR, we found that norepinephrine stimulation increases BAT blood flow in a dose-dependent manner, and that this response is profoundly modulated by environmental temperature acclimation. Surprisingly, we found that mice lacking uncoupling protein 1 (UCP1) have fully preserved BAT blood flow response to norepinephrine, despite failing to perform thermogenesis. BAT blood flow was not directly correlated to systemic glycaemia, but glucose injections could transiently increase tissue perfusion. Inguinal white adipose tissue, also known as a brite/beige adipose tissue, was also sensitive to cold acclimation and similarly increased blood flow in response to norepinephrine. In conclusion, using a novel non-invasive method to detect BAT perfusion, we demonstrate that adrenergically-stimulated BAT blood flow is qualitatively and quantitatively fully independent of thermogenesis, and is therefore not a reliable parameter for the estimation of BAT activation and heat generation.

Ort, förlag, år, upplaga, sidor
2015. Vol. 308, nr 9, s. E822-E829
Nyckelord [en]
blood flow, brown adipose tissue, high-resolution laser-Doppler imaging, thermogenesis, uncoupling protein 1
Nationell ämneskategori
Biologiska vetenskaper
Forskningsämne
fysiologi
Identifikatorer
URN: urn:nbn:se:su:diva-115869DOI: 10.1152/ajpendo.00494.2014ISI: 000353951700011OAI: oai:DiVA.org:su-115869DiVA, id: diva2:800510
Tillgänglig från: 2015-04-06 Skapad: 2015-04-06 Senast uppdaterad: 2022-02-23Bibliografiskt granskad
Ingår i avhandling
1. Thermal physiology and metabolism: Interplay between heat generation and energy homeostasis
Öppna denna publikation i ny flik eller fönster >>Thermal physiology and metabolism: Interplay between heat generation and energy homeostasis
2015 (Engelska)Doktorsavhandling, sammanläggning (Övrigt vetenskapligt)
Abstract [en]

Mammal metabolism is intimately connected to the maintenance of body temperature. While metabolic pathways invariably produce heat as a by-product, the natural heat present in the environment also plays a role in defining the adaptive metabolism and general physiology of an organism. This thesis aims to discuss basic aspects of energy expenditure and their interactions with energy stores and body composition. In Paper I, we apply a new technique – high-resolution laser-Doppler imaging – to describe physiological regulatory features of adrenergically-stimulated blood flow in brown adipose tissue, and evaluate the validity of blood flow as a parameter to estimate nonshivering thermogenesis. Paper II focuses on the central regulation of body temperature. In the absence of bombesin receptor subtype-3, mice present an altered neurological body temperature setpoint, while peripheral thermogenic capacity remains intact. We conclude that brown adipose tissue malfunction is not the cause of the hypothermia observed in this mouse model. Paper III incorporates measurements of body temperature to the energy expenditure of different sources: basal metabolic rate, physical activity, thermic effect of food, and cold-induced thermogenesis. We describe basic aspects of dynamic insulation, energetic costs of circadian variation and hypothesize that physical activity may change the body temperature setpoint. Paper IV describes methodological issues related to glucose tolerance tests in obese mice. We conclude that the erroneous scaling of doses may affect the interpretation of metabolic health in mouse models, and suggest a new methodology. Paper V describes the outcomes caused by the expression of the human Cidea protein in adipose tissue of mice and suggests that this protein may clarify the link between adipose tissue expansion and healthy obesity. Paper VI explores the dissociation between thiazolidinedione-induced adipose tissue “browning” and reduced blood glycaemia. We demonstrate that although this pharmacological class tends to induce some level of brown adipose tissue recruitment, this phenomenon does not define its antidiabetic effects.

Ort, förlag, år, upplaga, sidor
Stockholm: Department of Molecular Biosciences, The Wenner-Gren Institute, Stockholm University, 2015. s. 55
Nationell ämneskategori
Fysiologi
Forskningsämne
fysiologi
Identifikatorer
urn:nbn:se:su:diva-115874 (URN)978-91-7649-156-0 (ISBN)
Disputation
2015-05-13, Nordenskiöldsalen, Geovetenskapens hus, Svante Arrhenius väg 12, 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 4: Manuscript. Paper 5: Manuscript. Paper 6: Manuscript.

Tillgänglig från: 2015-04-20 Skapad: 2015-04-06 Senast uppdaterad: 2022-02-23Bibliografiskt granskad

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Abreu-Vieira, GustavoCannon, BarbaraNedergaard, Jan

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Abreu-Vieira, GustavoCannon, BarbaraNedergaard, Jan
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American Journal of Physiology. Endocrinology and Metabolism
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