Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

Blondin, Denis P.; Labbé, Sébastien M.; Noll, Christophe; Kunach, Margaret; Phoenix, Serge; Guérin, Brigitte; Turcotte, Éric; Haman, François; Richard, Denis; Carpentier, André C.

doi:10.2337/db14-1651

Cited by 186 publications

(222 citation statements)

References 40 publications

(52 reference statements)

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“…Our results confirm the ability to iWAT to undergo browning after chronic CL and cold and to exhibit increased mtDNA content. However, our results do not demonstrate that the browning of iWAT was paralleled by a major increase in its metabolic activity as assessed with a triad of PET tracers that have been proven to readily detect any metabolic changes in BAT (3,4,19,33) as well as in other metabolically active tissues such as heart or liver (2,8,21,29,46). The oxidative activity ([ 11 C]acetate) of iWAT following chronic CL and cold was not only trivial compared with that of iBAT, but it was also not higher than that of eWAT, which resisted browning.…”

Section: Discussioncontrasting

confidence: 41%

“…The use of this triad of PET tracers has proven to be invaluable to assess brown fat metabolism in laboratory rodents (19) and humans (3,4,33). Specifically, our study aimed at comparing the metabolic activity of iBAT, the most investigated classical BAT depot, with that of iWAT and eWAT, which are known to, respectively, undergo or resist browning following adrenergic stimulation (cold exposure or ␤-adrenergic agonism) (51).…”

Section: Discussionmentioning

confidence: 99%

“…11 C]acetate has proven to be a very reliable tool for detecting metabolic activity changes in the heart (2, 29), liver (8,46), skeletal muscle (21), cancer cells (28,34), and, more recently, in brown fat (3,4,19,33), even in humans, where the density of brown fat adipocytes appears not higher than that of beige fat in laboratory mice (55). One can also argue that either the mouse strain that we used was not a good responder to cold or the cold stimulus that we used did not sufficiently enhance iWAT thermogenic capacity.…”

Section: Discussionmentioning

confidence: 99%

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Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Labbé

Caron

Chechi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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Classical brown adipocytes such as those found in interscapular brown adipose tissue (iBAT) represent energy-burning cells, which have been postulated to play a pivotal role in energy metabolism. Brown adipocytes can also be found in white adipose tissue (WAT) depots [e.g., inguinal WAT (iWAT)] following adrenergic stimulation, and they have been referred to as “beige” adipocytes. Whether the presence of these adipocytes, which gives iWAT a beige appearance, can confer a white depot with some thermogenic activity remains to be seen. In consequence, we designed the present study to investigate the metabolic activity of iBAT, iWAT, and epididymal white depots in mice. Mice were either 1) kept at thermoneutrality (30°C), 2) kept at 30°C and treated daily for 14 days with an adrenergic agonist [CL-316,243 (CL)], or 3) housed at 10°C for 14 days. Metabolic activity was assessed using positron emission tomography imaging with fluoro-[18F]deoxyglucose (glucose uptake), fluoro-[18F]thiaheptadecanoic acid (fatty acid uptake), and [11C]acetate (oxidative activity). In each group, substrate uptakes and oxidative activity were measured in anesthetized mice in response to acute CL. Our results revealed iBAT as a major site of metabolic activity, which exhibited enhanced glucose and nonesterified fatty acid uptakes and oxidative activity in response to chronic cold and CL. On the other hand, beige adipose tissue failed to exhibit appreciable increase in oxidative activity in response to chronic cold and CL. Altogether, our results suggest that the contribution of beige fat to acute-CL-induced metabolic activity is low compared with that of iBAT, even after sustained adrenergic stimulation.

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Section: Discussioncontrasting

confidence: 41%

Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

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Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Labbé

Caron

Chechi

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

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“…As such, using dedicated cooling protocols to activate BAT, we have shown that BAT is present and active upon acute exposure to cold in 90-100% of lean, young adults and that BAT activity is related to nonshivering thermogenesis (NST) (10,11). In addition, several studies have reported negative relations between BAT activity and age and body fatness in humans (3,12), likely the result of the "whitening" of classical BAT depots (13), most notably the supraclavicular BAT depot. Interestingly, both older age (14) and obesity (15) are also associated with a blunted NST response upon exposure to mild cold.…”

Section: Short-term Cold Acclimation Recruits Brown Adipose Tissue Inmentioning

confidence: 99%

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans

et al. 2015

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Recruitment of brown adipose tissue (BAT) has emerged as a potential tool to combat obesity and associated metabolic complications. Short-term cold acclimation has been shown not only to enhance the presence and activity of BAT in lean humans but also to improve the metabolic profile of skeletal muscle to benefit glucose uptake in patients with type 2 diabetes. Here we examined whether short-term cold acclimation also induced such adaptations in 10 metabolically healthy obese male subjects. A 10-day cold acclimation period resulted in increased cold-induced glucose uptake in BAT, as assessed by [18F]fluorodeoxyglucose positron emission tomography/computed tomography. BAT activity was negatively related to age, with a similar trend for body fat percentage. In addition, cold-induced glucose uptake in BAT was positively related to glucose uptake in visceral white adipose tissue, although glucose uptake in visceral and subcutaneous white adipose tissue depots was unchanged upon cold acclimation. Cold-induced skeletal muscle glucose uptake tended to increase upon cold acclimation, which was paralleled by increased basal GLUT4 localization in the sarcolemma, as assessed through muscle biopsies. Proximal skin temperature was increased and subjective responses to cold were slightly improved at the end of the acclimation period. These metabolic adaptations to prolonged exposure to mild cold may lead to improved glucose metabolism or prevent the development of obesity-associated insulin resistance and hyperglycemia.

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“…14 Over the past decade, human BAT has become a hot research field, not only because it was discovered that BAT is active in human adults but also because it contributes to energy metabolism 19,20 and its activity inversely correlates with body mass index and body fat mass, 15,16,[21][22][23] suggesting a role for BAT in human energy expenditure. In fact, BAT activation by means of repeated cold exposure enhances nonshivering thermogenesis 24 and lowers fat mass, 25 providing proof of principle that activation of BAT in humans can reduce obesity.…”

Section: Discovery Of Bat In Adult Humansmentioning

confidence: 99%

Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis

Hoeke

Kooijman

Boon

et al. 2016

Circulation Research

146

138

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Atherosclerosis, for which hyperlipidemia is a major risk factor, is the leading cause of morbidity and mortality in Western society, and new therapeutic strategies are highly warranted. Brown adipose tissue (BAT) is metabolically active in human adults. Although positron emission tomography-computed tomography using a glucose tracer is the golden standard to visualize and quantify the volume and activity of BAT, it has become clear that activated BAT combusts fatty acids rather than glucose. Here, we review the role of brown and beige adipocytes in lipoprotein metabolism and atherosclerosis, with evidence derived from both animal and human studies. On the basis of mainly data from animal models, we propose a model in which activated brown adipocytes use their intracellular triglyceride stores to generate fatty acids for combustion. BAT rapidly replenishes these stores by internalizing primarily lipoprotein triglyceride-derived fatty acids, generated by lipoprotein lipasemediated hydrolysis of triglycerides, rather than by holoparticle uptake. As a consequence, BAT activation leads to the generation of lipoprotein remnants that are subsequently cleared via the liver provided that an intact apoElow-density lipoprotein receptor pathway is present. Through these mechanisms, BAT activation reduces plasma triglyceride and cholesterol levels and attenuates diet-induced atherosclerosis development. Initial studies suggest that BAT activation in humans may also reduce triglyceride and cholesterol levels, but potential antiatherogenic effects should be assessed in future studies. (Circ Res. 2016;118:173-182.

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Selective Impairment of Glucose but Not Fatty Acid or Oxidative Metabolism in Brown Adipose Tissue of Subjects With Type 2 Diabetes

Cited by 186 publications

References 40 publications

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Metabolic activity of brown, “beige,” and white adipose tissues in response to chronic adrenergic stimulation in male mice

Short-term Cold Acclimation Recruits Brown Adipose Tissue in Obese Humans

Role of Brown Fat in Lipoprotein Metabolism and Atherosclerosis

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