Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans)

Cannon, Barbara; Nedergaard, Jan

doi:10.1038/ijo.2010.177

Cited by 155 publications

(144 citation statements)

References 71 publications

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“…18 In this study, we observed that mRNA expression of Adrb3 in retroperitoneal fat was significantly higher in HFD than ND rats. Upregulation of Adrb3 is consistent with previous research demonstrating that adrenergic stimulation 8 via the b 3 -adrenergic receptor has a key role in brown fat activation and subsequent energy dissipation, 8 as well as emergence of brown fat in WAT. 20,39,46 Further, islands of brown adipocytes in WAT are richly sympathetically innervated.…”

Section: Discussionsupporting

confidence: 91%

“…1 Obesity is defined by the expansion of white adipose tissue (WAT), but recent evidence suggests that the adult human body also contains functionally distinct, brown adipose tissue. [2][3][4][5][6][7][8] In contrast to WAT, which has a primary role in energy storage, brown adipose tissue specializes in energy dissipation as heat (Cannon and Nedergaard 9 ). This thermogenic property of brown fat results from its high content of mitochondria, cell organelles where energy dissipation occurs.…”

Section: Introductionmentioning

confidence: 99%

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High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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Obesity has a profound adverse impact on health. In this study, we present evidence for high-fat diet (HFD)-induced emergence of brown-like adipocytes in white adipose tissue (WAT) of the spontaneously hypertensive rat (SHR). We studied adult males fed a HFD or normal diet (ND) for 12 weeks. At the end of the 12-week dietary intervention, HFD compared with ND rats showed significantly higher whole-body energy expenditure. HFD vs. ND rats also showed higher expression of genes involved in fatty acid oxidation, mitochondrial biogenesis and brown fat adipogenesis, as well as augmented mitochondrial mass in WAT but not in the liver or skeletal muscle. Consistent with the molecular changes, in HFD but not in ND rats, histological and immunohistochemistry-based analyses of WAT demonstrated the presence of small multilocular cells staining positively for uncoupling protein 1, indicating the emergence of brown-like adipocytes in WAT. Our results suggest that SHR may have the capacity to increase energy expenditure in response to a chronic HFD that may be linked to the emergence of brown-like adipocytes in WAT. Thus, the SHR may be an important genetic model to uncover novel mechanisms of resistance to dietary obesity.

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Section: Discussionsupporting

confidence: 91%

Section: Introductionmentioning

confidence: 99%

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

et al. 2011

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“…Moreover, shivering decreases during cold exposure after ∼2 weeks [47] and cold-stimulated activity has been shown to vary seasonally [4]. However, it remains unknown whether all or a portion of these effects can be directly attributed to adaptive BAT thermogenesis [48].…”

Section: Therapeutic Implicationsmentioning

confidence: 99%

Ephedrine activates brown adipose tissue in lean but not obese humans

et al. 2012

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Aims/hypothesis Brown adipose tissue (BAT) activation increases energy consumption and may help in the treatment of obesity. Cold exposure is the main physiological stimulus for BAT thermogenesis and the sympathetic nervous system, which innervates BAT, is essential in this process. However, cold-induced BAT activation is impaired in obese humans. To explore the therapeutic potential of BAT, it is essential to determine whether pharmacological agents can activate BAT. Methods We aimed to determine whether BAT can be activated in lean and obese humans after acute administration of an orally bioavailable sympathomimetic. In a randomised, double-blinded, crossover trial, we administered 2.5 mg/kg of oral ephedrine to nine lean (BMI 22±1 kg/m 2 ) and nine obese (BMI 36±1 kg/m 2 ) young men. On a separate day, a placebo was administered to the same participants. BAT activity was assessed by measuring glucose uptake with [ 18 F]fluorodeoxyglucose and positron emission tomography-computed tomography imaging.

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“…However, whether the capacity to stimulate glucose uptake into BAT is also reduced under insulinresistant conditions is presently unknown. Since BAT relies on both carbohydrate and lipid oxidation for its heat production [21], an impaired glucose uptake under fasting-induced insulin-resistant conditions would hamper its thermogenic capacity and could lead to reduced capacity to defend body temperature upon cold exposure. On the other hand, if glucose uptake into BAT could be stimulated by cold exposure under such insulin-resistant conditions, activation of glucose uptake into BAT by cold exposure or other means could serve as an interesting target to increase glucose clearance during insulin resistance.…”

Section: Introductionmentioning

confidence: 99%

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

et al. 2014

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Aims/hypothesis Human brown adipose tissue (BAT) has recently emerged as a potential target in the treatment of type 2 diabetes, owing to its capacity to actively clear glucose from the circulation-at least upon cold exposure. The effects of insulin resistance on the capacity of human BAT to take up glucose are unknown. Prolonged fasting is known to induce insulin resistance in peripheral tissues in order to spare glucose for the brain. Methods We studied the effect of fasting-induced insulin resistance on the capacity of BAT to take up glucose during cold exposure as well as on cold-stimulated thermogenesis. BAT glucose uptake was assessed by means of cold-stimulated dynamic 2-deoxy-2-[ 18 F]fluoro-D-glucose positron emission tomography/computed tomography ([ 18 F]FDG-PET/CT) imaging.Results We show that a 54 h fasting period markedly decreases both cold-induced BAT glucose uptake and nonshivering thermogenesis (NST) during cold stimulation. In vivo molecular imaging and modelling revealed that the reduction of glucose uptake in BAT was due to impaired cellular glucose uptake and not due to decreased supply. Interestingly, decreased BAT glucose uptake upon fasting was related to a decrease in core temperature during cold exposure, pointing towards a role for BAT in maintaining normothermia in humans. Conclusions/interpretation Cold-stimulated glucose uptake in BAT is strongly reduced upon prolonged fasting. When cold-stimulated glucose uptake in BAT is also reduced under other insulin-resistant states, such as diabetes, cold-induced activation of BAT may not be a valid way to improve glucose clearance by BAT under such conditions. Trial registration: www.trialregister.nl NTR3523 Funding: This work was supported by the EU FP7 project DIABAT (HEALTH-F2-2011-278373

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Metabolic consequences of the presence or absence of the thermogenic capacity of brown adipose tissue in mice (and probably in humans)

Cited by 155 publications

References 71 publications

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

High-fat diet induces emergence of brown-like adipocytes in white adipose tissue of spontaneously hypertensive rats

Ephedrine activates brown adipose tissue in lean but not obese humans

Glucose uptake in human brown adipose tissue is impaired upon fasting-induced insulin resistance

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