Activation of brown adipose tissue thermogenesis in recovery from anesthetic hypothermia in rats

Changes of brown adipose tissue (BAT) thermogenesis in the recovery from anesthetic hypothermia were studied by measuring the temperatures of the interscapular BAT and rectum or the tissue uptake of 2-deoxyglucose (2-DG) in rats. After intraperitoneal injection of pentobarbital sodium (50 mg/kg), rectal temperature decreased to reach a steady level of approximately 33 degrees C (steady phase) and then increased gradually (recovery phase). The temperature of the interscapular BAT was significantly higher than rectal temperature in the recovery phase. The uptake of 2-DG in vivo in BAT was low in the steady phase but increased greatly in the recovery phase. The increase in 2-DG uptake was suppressed after surgical sympathetic denervation or when rectal temperature was maintained at approximately 37.5 degrees C. In the heart, skeletal muscle, and white adipose tissue, there was no appreciable change in 2-DG uptake except a slight increase in the heart. beta-Adrenergic blockade attenuated the changes in BAT temperature and 2-DG uptake seen during the recovery phase. It was concluded that BAT significantly contributes to heat production in recovery from anesthetic hypothermia.

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Median preoptic area neurons are required for the cooling and febrile activations of brown adipose tissue thermogenesis in rat

Scientific Reports ◽

10.1038/s41598-020-74272-w ◽

2020 ◽

Vol 10 (1) ◽

Author(s):

Ellen Paula Santos da Conceição ◽

Shaun F. Morrison ◽

Georgina Cano ◽

Pierfrancesco Chiavetta ◽

Domenico Tupone

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Energy Homeostasis ◽

Preoptic Area ◽

Therapeutic Approaches ◽

Dorsomedial Hypothalamus ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

Abstract Within the central neural circuitry for thermoregulation, the balance between excitatory and inhibitory inputs to the dorsomedial hypothalamus (DMH) determines the level of activation of brown adipose tissue (BAT) thermogenesis. We employed neuroanatomical and in vivo electrophysiological techniques to identify a source of excitation to thermogenesis-promoting neurons in the DMH that is required for cold defense and fever. Inhibition of median preoptic area (MnPO) neurons blocked the BAT thermogenic responses during both PGE2-induced fever and cold exposure. Disinhibition or direct activation of MnPO neurons induced a BAT thermogenic response in warm rats. Blockade of ionotropic glutamate receptors in the DMH, or brain transection rostral to DMH, blocked cold-evoked or NMDA in MnPO-evoked BAT thermogenesis. RNAscope technique identified a glutamatergic population of MnPO neurons that projects to the DMH and expresses c-Fos following cold exposure. These discoveries relative to the glutamatergic drive to BAT sympathoexcitatory neurons in DMH augment our understanding of the central thermoregulatory circuitry in non-torpid mammals. Our data will contribute to the development of novel therapeutic approaches to induce therapeutic hypothermia for treating drug-resistant fever, and for improving glucose and energy homeostasis.

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Food restriction increases torpor and improves brown adipose tissue thermogenesis in ob/ob mice

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1985.248.5.e531 ◽

1985 ◽

Vol 248 (5) ◽

pp. E531-E539 ◽

Cited By ~ 19

Author(s):

J. Himms-Hagen

Keyword(s):

Adipose Tissue ◽

Body Temperature ◽

Brown Adipose Tissue ◽

Rectal Temperature ◽

Food Restriction ◽

Normal Body Temperature ◽

Cold Intolerance ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis ◽

Ad Libitum

Restricting the food intake of the genetically obese (ob/ob) mouse is known to ameliorate its cold intolerance. Cold intolerance of the ob/ob mouse is associated with defective thermogenesis in its brown adipose tissue. The objective of the experiments was to find out whether food restriction could increase the thermogenic function of brown adipose tissue of the ob/ob mouse. Obese and lean mice were fed a restricted amount of chow in one meal per day for 3-7 mo. Both lean and ob/ob mice were torpid (rectal temperature of approximately 32 degrees C) in the early morning and aroused spontaneously to a normal body temperature before the anticipated meal time. Obese mice were also torpid during the dark phase, whereas lean mice were active and had a normal body temperature at this time. Brown adipose tissue was in a thermogenically inactive state (low level of mitochondrial GDP binding) in torpid lean and ob/ob mice but became thermogenically active (increase in mitochondrial GDP binding) during stimulated arousal when body temperature increased by 6-7 degrees C in 15-30 min. Ad libitum-fed ob/ob mice had a normal diurnal rhythm in a rectal temperature that was at a lower level than in lean ad libitum-fed mice. They did not raise their rectal temperatures when stimulated and no activation of brown adipose tissue thermogenesis occurred under these conditions. Food restriction increased the capacity of both lean and ob/ob mice to raise their metabolic rate in response to injection of noradrenaline, indicating an increased capacity for thermogenesis in their brown adipose tissue.(ABSTRACT TRUNCATED AT 250 WORDS)

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Brown adipose tissue—a factor in the survival of harp seal pups

Canadian Journal of Physiology and Pharmacology ◽

10.1139/y76-057 ◽

1976 ◽

Vol 54 (3) ◽

pp. 409-412 ◽

Cited By ~ 27

Author(s):

Hans J. Grav ◽

Arnoldus Schytte Blix

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Artificial Respiration ◽

Decisive Role ◽

The Body ◽

Harp Seal ◽

Adrenergic Blockade ◽

Brown Adipose ◽

Ice Water

The respiratory characteristics of mitochondria isolated from the subcutaneous brown adipose tissue of newborn harp seals indicate that the tissue is thermogenically active. Temperature recordings in vivo revealed, in fact, that the tissue was maintained at a temperature close to that of the body core during immersion of the pups in ice-water. Beta-adrenergic blockade markedly increased the cooling rates at both locations in ice-water, while curarization, accompanied by artificial respiration did not. We conclude that nonshivering thermogenesis through activated brown adipose tissue plays a decisive role in the defence against cold in the newborn harp seal.

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Glucocorticoids modulate human brown adipose tissue thermogenesis in vivo

Metabolism ◽

10.1016/j.metabol.2017.01.024 ◽

2017 ◽

Vol 70 ◽

pp. 125-132 ◽

Cited By ~ 28

Author(s):

Hannah Scotney ◽

Michael E. Symonds ◽

James Law ◽

Helen Budge ◽

Don Sharkey ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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A YY1 phosphorylation switch in brown adipose tissue orchestrates energy homeostasis.

10.21203/rs.3.rs-523586/v1 ◽

2021 ◽

Author(s):

Zyanya Díaz-Hirashi ◽

Tian Gao ◽

Chiara Scaffidi ◽

Monika Fey ◽

Susan Murray ◽

...

Keyword(s):

Adipose Tissue ◽

Energy Balance ◽

Brown Adipose Tissue ◽

Transcriptional Control ◽

Energy Homeostasis ◽

Whole Body ◽

Regulatory Subunit ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

Abstract Whole-body energy homeostasis is influenced by anabolic and catabolic cellular programs, which depend on environmental and nutritional cues. Adipose tissue plays a predominant role in the physiological regulation of energy balance by either storing or consuming energy through brown adipose tissue thermogenesis. It is however not clearly understood how brown adipose tissue balances catabolic and anabolic states. We show here that the transcription factor YY1 senses energetic state through a post-translational S120 phosphorylation switch. Adrenergic signaling leads to YY1 dephosphorylation which directly activates thermogenesis and a catabolic gene program while its phosphorylation maintains an anabolic program. Mechanistically, YY1 dephosphorylation increases chromatin binding at distal genomic loci respective to the transcription start site but remains constitutively bound to TSS. This mode of transcriptional control influences the activating and repressive function of YY1 and regulates catabolism/anabolism. We show that YY1 interacts with PPP1R3B, a regulatory subunit of the phosphatase PP1 and that in vivo knockdown of PPP1R3B protects against diet-induced obesity and insulin resistance. Our results uncover a novel transcriptional mechanism of metabolism orchestrated by YY1 phosphorylation switch and identifies PPP1R3B as a regulator of energy balance.

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In vivo measurement of energy substrate contribution to cold‐induced brown adipose tissue thermogenesis

The FASEB Journal ◽

10.1096/fj.14-266247 ◽

2015 ◽

Vol 29 (5) ◽

pp. 2046-2058 ◽

Cited By ~ 116

Author(s):

Sébastien M. Labbé ◽

Alexandre Caron ◽

Inan Bakan ◽

Mathieu Laplante ◽

André C. Carpentier ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Energy Substrate ◽

In Vivo Measurement ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Effects of 4-hydroxyamphetamine on in vivo brown adipose tissue thermogenesis and feeding behavior in the rat.

Behavioral Neuroscience ◽

10.1037/0735-7044.98.6.1060 ◽

1984 ◽

Vol 98 (6) ◽

pp. 1060-1064 ◽

Cited By ~ 4

Author(s):

Paul J. Wellman ◽

Patricia A. Watkins-Freeman

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Feeding Behavior ◽

Brown Adipose ◽

Brown Adipose Tissue Thermogenesis

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Functional characterization of human brown adipose tissue metabolism

Biochemical Journal ◽

10.1042/bcj20190464 ◽

2020 ◽

Vol 477 (7) ◽

pp. 1261-1286 ◽

Cited By ~ 3

Author(s):

Marie Anne Richard ◽

Hannah Pallubinsky ◽

Denis P. Blondin

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Functional Characterization ◽

Human Infants ◽

Positron Emission ◽

Brown Adipose ◽

Treatment Of Obesity ◽

And Function

Brown adipose tissue (BAT) has long been described according to its histological features as a multilocular, lipid-containing tissue, light brown in color, that is also responsive to the cold and found especially in hibernating mammals and human infants. Its presence in both hibernators and human infants, combined with its function as a heat-generating organ, raised many questions about its role in humans. Early characterizations of the tissue in humans focused on its progressive atrophy with age and its apparent importance for cold-exposed workers. However, the use of positron emission tomography (PET) with the glucose tracer [18F]fluorodeoxyglucose ([18F]FDG) made it possible to begin characterizing the possible function of BAT in adult humans, and whether it could play a role in the prevention or treatment of obesity and type 2 diabetes (T2D). This review focuses on the in vivo functional characterization of human BAT, the methodological approaches applied to examine these features and addresses critical gaps that remain in moving the field forward. Specifically, we describe the anatomical and biomolecular features of human BAT, the modalities and applications of non-invasive tools such as PET and magnetic resonance imaging coupled with spectroscopy (MRI/MRS) to study BAT morphology and function in vivo, and finally describe the functional characteristics of human BAT that have only been possible through the development and application of such tools.

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