The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

Broeders, Evie P. M.; Nascimento, Emmani B. M.; Havekes, Bas; Brans, Boudewijn; Roumans, Kay H. M.; Tailleux, Anne; Schaart, Gert; Kouach, Mostafa; Charton, Julie; Deprez, Benoı̂t; Bouvy, Nicole D.; Mottaghy, Felix M.; Staels, Bart; Lichtenbelt, Wouter D. van Marken; Schrauwen, Patrick

doi:10.1016/j.cmet.2015.07.002

Cited by 346 publications

(296 citation statements)

References 38 publications

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“…In humans, two oral ingestions of the primary bile acid chenodeoxycholic acid (CDCA) within 24 h enhanced coldinduced glucose uptake into BAT. In support of this thermogenic action, CDCA also triggered increased uncoupled leak respiration in primary brown adipocytes upon acute treatment (Broeders et al, 2015). The latter observation was also reported for human skeletal muscle cells (Watanabe et al, 2006); however, to date, such acute activation has not been demonstrated in mice.…”

Section: Bile Acidssupporting

confidence: 58%

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Braun

Oeckl

Westermeier

et al. 2018

Journal of Experimental Biology

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The enormous plasticity of adipose tissues, to rapidly adapt to altered physiological states of energy demand, is under neuronal and endocrine control. In energy balance, lipolysis of triacylglycerols and re-esterification of free fatty acids are opposing processes operating in parallel at identical rates, thus allowing a more dynamic transition from anabolism to catabolism, and vice versa. In response to alterations in the state of energy balance, one of the two processes predominates, enabling the efficient mobilization or storage of energy in a negative or positive energy balance, respectively. The release of noradrenaline from the sympathetic nervous system activates lipolysis in a depot-specific manner by initiating the canonical adrenergic receptor-G s -protein-adenylyl cyclase-cyclic adenosine monophosphate-protein kinase A pathway, targeting proteins of the lipolytic machinery associated with the interface of the lipid droplets. In brown and brite adipocytes, lipolysis stimulated by this signaling pathway is a prerequisite for the activation of non-shivering thermogenesis. Free fatty acids released by lipolysis are direct activators of uncoupling protein 1-mediated leak respiration. Thus, pro-and anti-lipolytic mediators are bona fide modulators of thermogenesis in brown and brite adipocytes. In this Review, we discuss adrenergic and non-adrenergic mechanisms controlling lipolysis and thermogenesis and provide a comprehensive overview of pro-and anti-lipolytic mediators.

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Section: Bile Acidssupporting

confidence: 58%

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Braun

Oeckl

Westermeier

et al. 2018

Journal of Experimental Biology

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“…[35][36][37] In this study, we found that even some individuals over their fifties had BAT-positive rates of 15% to 25%, and this suggests the possibility to maintain and/or increase the BAT-d even in relatively older individuals. However, the effect of genetic predispositions cannot be ruled out for individuals with a higher BAT-d.…”

Section: Discussionmentioning

confidence: 49%

Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range

et al. 2018

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"Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range," J. Biomed. Opt. 23(6), 065002 (2018), doi: 10.1117/1.JBO.23.6.065002. Abstract. 18 F-fluorodeoxyglucose (FDG)-positron emission tomography (PET) along with computed tomography (CT) is a standard method for assessing brown adipose tissue (BAT) activity. We tested the usefulness of near-infrared time-resolved spectroscopy (NIR TRS ) as a simple and noninvasive method for evaluating BAT density (BAT-d) by examining the effects of some factors known to influence BAT activity. The total hemoglobin concentration as a parameter of BAT-d was evaluated using NIR TRS in the supraclavicular region in 413 Japanese individuals. The associations were analyzed between BAT-d and sex, age, the percentages of body fat (%BF), visceral fat (VF), and the seasonal ambient temperature (AmT) fluctuations. Age was associated with decreased BAT-d (P < 0.05). There was no sex difference in the BAT-d, except for those in their twenties. Multivariate analyses revealed that %BF and VF were correlated with BAT-d, and the lower AmT (around 4°C or 5°C) for 4 and 6 weeks prior to the measurement day was associated with an increase in the BAT-d. Our NIR TRS results were analogous to those reported with 18 FDG-PET∕CT, indicating the usefulness of NIR TRS . BAT-d might increase during the 4 and 6 weeks after the AmT decreases to lower than 4°C or 5°C. © The Authors. Published by SPIE under a Creative Commons Attribution 3.0 Unported License. Distribution or reproduction of this work in whole or in part requires full attribution of the original publication, including its DOI.

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“…In this regard, it has been reported that BAs exert pleiotropic effects on metabolism, including activation of BAT leading to increased energy expenditure, which has prevented obesity and insulin resistance during HFD feeding (41). In humans, it has recently been reported that BAs activate BAT and increase energy expenditure (42). These effects of BA are mediated by the GPBAR1 (TGR5) receptor and dependent on the induction of DIO2 (42), expression of which was increased in BAT from aP2/Alox5ap transgenic mice.…”

Section: Discussionmentioning

confidence: 99%

“…3L). BAs have been shown to increase brown fat activity and energy expenditure through the G-protein-coupled BA receptor 1 (GPBAR1) (also called TGR5) and the activation of type 2 iodothyronine deionidase (DIO2) (41,42). In BAT from aP2/Alox5ap mice, Gpbar1 expression levels were higher and Dio2 expression showed a tendency to increase (Fig.…”

Section: Ap2/alox5ap Transgenic Mice Present Higher Levels Of Bas In mentioning

confidence: 99%

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance

et al. 2016

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Eicosanoids, such as leukotriene B4 (LTB4) and lipoxin A4 (LXA4), may play a key role during obesity. While LTB4 is involved in adipose tissue inflammation and insulin resistance, LXA4 may exert anti-inflammatory effects and alleviate hepatic steatosis. Both lipid mediators derive from the same pathway, in which arachidonate 5-lipoxygenase (ALOX5) and its partner, arachidonate 5-lipoxygenase–activating protein (ALOX5AP), are involved. ALOX5 and ALOX5AP expression is increased in humans and rodents with obesity and insulin resistance. We found that transgenic mice overexpressing ALOX5AP in adipose tissue had higher LXA4 rather than higher LTB4 levels, were leaner, and showed increased energy expenditure, partly due to browning of white adipose tissue (WAT). Upregulation of hepatic LXR and Cyp7a1 led to higher bile acid synthesis, which may have contributed to increased thermogenesis. In addition, transgenic mice were protected against diet-induced obesity, insulin resistance, and inflammation. Finally, treatment of C57BL/6J mice with LXA4, which showed browning of WAT, strongly suggests that LXA4 is responsible for the transgenic mice phenotype. Thus, our data support that LXA4 may hold great potential for the future development of therapeutic strategies for obesity and related diseases.

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The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

Cited by 346 publications

References 38 publications

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Brown adipose tissue density measured by near-infrared time-resolved spectroscopy in Japanese, across a wide age range

ALOX5AP Overexpression in Adipose Tissue Leads to LXA4 Production and Protection Against Diet-Induced Obesity and Insulin Resistance

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