A randomized trial of cold-exposure on energy expenditure and supraclavicular brown adipose tissue volume in humans

Serotonin (5-HT) and thyroid hormones are part of a complex system modulating eating behaviour and energy expenditure. 5'-Deiodinase (5'-D) converts the relatively inactive thyroxine (T4) to triiodothyronine (T3), and its activity is an indirect measure of T3 production in peripheral tissues, particularly in the brain, intrascapular brown adipose tissue (IBAT), heart, liver, and kidney. We evaluated the effect of 5-HT on 5'-D activity during basal conditions and after short (30 min) cold exposure (thyroid stimulating hormone stimulation test, TST). 5'-D activity was assessed in the liver, heart, brain, kidney, and IBAT. TST increases 5'-D activity in the brain, heart, and IBAT and decreases it in kidney, leaving it unchanged in the liver. 5-HT alone did not modify 5'-D activity in the organs under study but decreased it in the IBAT, heart, and brain when injected before the TST was administered. Our results confirm the important role of 5-HT in thermoregulation, given its peripheral site of action, in modulating heat production controlling intracellular T3 production. These effects are more evident when heat production is upregulated during cold exposure in organs containing type II 5'-D, such as the brain, heart, and IBAT, which are able to modify their function during conditions that alter energy balance. In conclusion, 5-HT may also act peripherally directly on the thyroid and organs containing type II 5'-D, thus controlling energy expenditure through heat production.Key words: serotonin, deiodinase activity, thyroid hormone, brown adipose tissue, thermogenesis, rat organs.

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The Presence of Active Brown Adipose Tissue Determines Cold-Induced Energy Expenditure and Oxylipin Profiles in Humans

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/clinem/dgaa183 ◽

2020 ◽

Vol 105 (7) ◽

pp. 2203-2216 ◽

Cited By ~ 7

Author(s):

Oana C Kulterer ◽

Laura Niederstaetter ◽

Carsten T Herz ◽

Alexander R Haug ◽

Andrea Bileck ◽

...

Keyword(s):

Fatty Acids ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Fdg Pet ◽

Brown Adipose ◽

Pet Ct ◽

18F Fdg ◽

Fdg Pet Ct

Abstract Background Accumulating evidence links brown adipose tissue (BAT) to increased cold-induced energy expenditure (CIEE) and regulation of lipid metabolism in humans. BAT has also been proposed as a novel source for biologically active lipid mediators including polyunsaturated fatty acids (PUFAs) and oxylipins. However, little is known about cold-mediated differences in energy expenditure and various lipid species between individuals with detectable BAT positive (BATpos) and those without BAT negative (BATneg). Methods Here we investigated a unique cohort of matched BATpos and BATneg individuals identified by 18F-fluorodeoxyglucose positron emission tomography combined with computed tomography ([18F]-FDG PET/CT). BAT function, CIEE, and circulating oxylipins, were analyzed before and after short-term cold exposure using [18F]-FDG PET/CT, indirect calorimetry, and high-resolution mass spectrometry, respectively. Results We found that active BAT is the major determinant of CIEE since only BATpos individuals experienced significantly increased energy expenditure in response to cold. A single bout of moderate cold exposure resulted in the dissipation of an additional 20 kcal excess energy in BATpos but not in BATneg individuals. The presence of BAT was associated with a unique systemic PUFA and oxylipin profile characterized by increased levels of anti-inflammatory omega-3 fatty acids as well as cytochrome P450 products but decreased concentrations of some proinflammatory hydroxyeicosatetraenoic acids when compared with BATneg individuals. Notably, cold exposure raised circulating levels of various lipids, including the recently identified BAT-derived circulating factors (BATokines) DiHOME and 12-HEPE, only in BATpos individuals. Conclusions In summary, our data emphasize that BAT in humans is a major contributor toward cold-mediated energy dissipation and a critical organ in the regulation of the systemic lipid pool.

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Measurement of Human Brown Adipose Tissue Volume and Activity Using Anatomic MR Imaging and Functional MR Imaging

Journal of Nuclear Medicine ◽

10.2967/jnumed.112.117275 ◽

2013 ◽

Vol 54 (9) ◽

pp. 1584-1587 ◽

Cited By ~ 58

Author(s):

Y.-C. Iris Chen ◽

A. M. Cypess ◽

Y.-C. Chen ◽

M. Palmer ◽

G. Kolodny ◽

...

Keyword(s):

Adipose Tissue ◽

Mr Imaging ◽

Brown Adipose Tissue ◽

Tissue Volume ◽

Brown Adipose ◽

Functional Mr Imaging ◽

Adipose Tissue Volume

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Melatonin Increases Brown Adipose Tissue Volume and Activity in Patients With Melatonin Deficiency: A Proof-of-Concept Study

Diabetes ◽

10.2337/db18-0956 ◽

2019 ◽

Vol 68 (5) ◽

pp. 947-952 ◽

Cited By ~ 16

Author(s):

Bruno Halpern ◽

Marcio C. Mancini ◽

Clarissa Bueno ◽

Isabella P. Barcelos ◽

Maria Edna de Melo ◽

...

Keyword(s):

Adipose Tissue ◽

Brown Adipose Tissue ◽

Proof Of Concept ◽

Concept Study ◽

Tissue Volume ◽

Brown Adipose ◽

Adipose Tissue Volume

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Cold and Exercise: Therapeutic Tools to Activate Brown Adipose Tissue and Combat Obesity

Biology ◽

10.3390/biology8010009 ◽

2019 ◽

Vol 8 (1) ◽

pp. 9 ◽

Cited By ~ 8

Author(s):

Carmem Peres Valgas da Silva ◽

Diego Hernández-Saavedra ◽

Joseph White ◽

Kristin Stanford

Keyword(s):

Type 2 Diabetes ◽

Adipose Tissue ◽

Energy Expenditure ◽

Brown Adipose Tissue ◽

Cold Exposure ◽

Lipid Uptake ◽

Mitochondrial Uncoupling ◽

Bat Activity ◽

Brown Adipose

The rise in obesity over the last several decades has reached pandemic proportions. Brown adipose tissue (BAT) is a thermogenic organ that is involved in energy expenditure and represents an attractive target to combat both obesity and type 2 diabetes. Cold exposure and exercise training are two stimuli that have been investigated with respect to BAT activation, metabolism, and the contribution of BAT to metabolic health. These two stimuli are of great interest because they have both disparate and converging effects on BAT activation and metabolism. Cold exposure is an effective mechanism to stimulate BAT activity and increase glucose and lipid uptake through mitochondrial uncoupling, resulting in metabolic benefits including elevated energy expenditure and increased insulin sensitivity. Exercise is a therapeutic tool that has marked benefits on systemic metabolism and affects several tissues, including BAT. Compared to cold exposure, studies focused on BAT metabolism and exercise display conflicting results; the majority of studies in rodents and humans demonstrate a reduction in BAT activity and reduced glucose and lipid uptake and storage. In addition to investigations of energy uptake and utilization, recent studies have focused on the effects of cold exposure and exercise on the structural lipids in BAT and secreted factors released from BAT, termed batokines. Cold exposure and exercise induce opposite responses in terms of structural lipids, but an important overlap exists between the effects of cold and exercise on batokines. In this review, we will discuss the similarities and differences of cold exposure and exercise in relation to their effects on BAT activity and metabolism and its relevance for the prevention of obesity and the development of type 2 diabetes.

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