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Cidea improves the metabolic profile through expansion of adipose tissue
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut. University of Hamburg, Germany.
Stockholms universitet, Naturvetenskapliga fakulteten, Institutionen för molekylär biovetenskap, Wenner-Grens institut.ORCID-id: 0000-0001-8044-5410
Visa övriga samt affilieringar
Antal upphovsmän: 112015 (Engelska)Ingår i: Nature Communications, E-ISSN 2041-1723, Vol. 6, artikel-id 7433Artikel i tidskrift (Refereegranskat) Published
Abstract [en]

In humans, Cidea (cell death-inducing DNA fragmentation factor alpha-like effector A) is highly but variably expressed in white fat, and expression correlates with metabolic health. Here we generate transgenic mice expressing human Cidea in adipose tissues (aP2-hCidea mice) and show that Cidea is mechanistically associated with a robust increase in adipose tissue expandability. Under humanized conditions (thermoneutrality, mature age and prolonged exposure to high-fat diet), aP2-hCidea mice develop a much more pronounced obesity than their wild-type littermates. Remarkably, the malfunctioning of visceral fat normally caused by massive obesity is fully overcome-perilipin 1 and Akt expression are preserved, tissue degradation is prevented, macrophage accumulation is decreased and adiponectin expression remains high. Importantly, the aP2-hCidea mice display enhanced insulin sensitivity. Our data establish a functional role for Cidea and suggest that, in humans, the association between Cidea levels in white fat and metabolic health is not only correlative but also causative.

Ort, förlag, år, upplaga, sidor
2015. Vol. 6, artikel-id 7433
Nationell ämneskategori
Cellbiologi Cell- och molekylärbiologi
Forskningsämne
fysiologi
Identifikatorer
URN: urn:nbn:se:su:diva-119248DOI: 10.1038/ncomms8433ISI: 000357176500005OAI: oai:DiVA.org:su-119248DiVA, id: diva2:846115
Tillgänglig från: 2015-08-14 Skapad: 2015-08-03 Senast uppdaterad: 2023-03-28Bibliografiskt 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, GustavoFischer, Alexander W.de Jong, Jasper M. A.Shabalina, Irina G.Cannon, BarbaraNedergaard, JanPetrovic, Natasa

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Abreu-Vieira, GustavoFischer, Alexander W.de Jong, Jasper M. A.Shabalina, Irina G.Cannon, BarbaraNedergaard, JanPetrovic, Natasa
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Institutionen för molekylär biovetenskap, Wenner-Grens institut
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Nature Communications
CellbiologiCell- och molekylärbiologi

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