| 1. |
- Abreu-Vieira, Gustavo, 1987-, et al.
(författare)
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Adrenergically-stimulated blood flow in brown adipose tissue is not dependent on thermogenesis : Regulation of brown adipose tissue blood flow
- 2015
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Ingår i: American Journal of Physiology. Endocrinology and Metabolism. - : American Physiological Society. - 0193-1849 .- 1522-1555. ; 308:9, s. E822-E829
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 2. |
- Abreu-Vieira, Gustavo, et al.
(författare)
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Cidea improves the metabolic profile through expansion of adipose tissue
- 2015
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 6
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Tidskriftsartikel (refereegranskat)abstract
- 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.
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| 3. |
- Abreu-Vieira, Gustavo, 1987-, et al.
(författare)
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Integration of body temperature into the analysis of energy expenditure in the mouse
- 2015
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Ingår i: Molecular Metabolism. - : Elsevier BV. - 2212-8778. ; 4:6, s. 461-470
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: We quantified the effect of environmental temperature on mouse energy homeostasis and body temperature.Methods: The effect of environmental temperature (4e33 C) on body temperature, energy expenditure, physical activity, and food intake invarious mice (chow diet, high-fat diet, Brs3-/y, lipodystrophic) was measured using continuous monitoring.Results: Body temperature depended most on circadian phase and physical activity, but also on environmental temperature. The amounts ofenergy expenditure due to basal metabolic rate (calculated via a novel method), thermic effect of food, physical activity, and cold-inducedthermogenesis were determined as a function of environmental temperature. The measured resting defended body temperature matchedthat calculated from the energy expenditure using Fourier’s law of heat conduction. Mice defended a higher body temperature during physicalactivity. The cost of the warmer body temperature during the active phase is 4e16% of total daily energy expenditure. Parameters measured indiet-induced obese and Brs3-/y mice were similar to controls. The high post-mortem heat conductance demonstrates that most insulation in miceis via physiological mechanisms.Conclusions: At 22 C, cold-induced thermogenesis isw120% of basal metabolic rate. The higher body temperature during physical activity isdue to a higher set point, not simply increased heat generation during exercise. Most insulation in mice is via physiological mechanisms, with littlefrom fur or fat. Our analysis suggests that the definition of the upper limit of the thermoneutral zone should be re-considered. Measuring bodytemperature informs interpretation of energy expenditure data and improves the predictiveness and utility of the mouse to model human energyhomeostasis.
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| 4. |
- Abreu-Vieira, Gustavo, 1987-
(författare)
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Thermal physiology and metabolism : Interplay between heat generation and energy homeostasis
- 2015
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- 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.
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