Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice

Teodoro, João S.; Zouhar, Petr; Flachs, Pavel; Bardová, Kristina; Janovská, Petra; Gomes, Ana P.; Duarte, Filipe V.; Varela, Ana; Rolo, Anabela P.; Palmeira, Carlos M.; Kopecký, Jan

doi:10.1038/ijo.2013.230

Cited by 63 publications

(72 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…This may mean that the magnitude of the increase in EE caused by iBAT nonshivering thermogenesis over a period of several weeks cannot be detected by indirect calorimetry but can be detected by the energy balance methodology of Ravussin et al (21). An additional question in the studies by both Watanabe et al (27) and Teodoro et al (24) comes from the lack of information on the ambient temperature in the former study, whereas the latter study was conducted at an ambient temperature of 20°C. Accordingly, does the EE/ thermogenic mechanism involve an interaction between the BAs, thyroid, and cold-activated adrenergic-mediated signaling pathways of thermogenesis?…”

Section: E349contrasting

confidence: 41%

“…The problem with the data of Watanabe et al (27) has been discussed by Teodoro et al (24), who, parenthetically, did not detect an increase in EE in mice fed BAs. Although Teodoro et al (24) showed a robust induction of Ucp1 expression in mice treated with BAs, whole body EE, as determined by indirect calorimetry, was not increased in diet-induced obese mice treated with BA. This may mean that the magnitude of the increase in EE caused by iBAT nonshivering thermogenesis over a period of several weeks cannot be detected by indirect calorimetry but can be detected by the energy balance methodology of Ravussin et al (21).…”

Section: E349mentioning

confidence: 99%

See 1 more Smart Citation

Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice

Ziętak

Kozak

2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Zietak M, Kozak LP. Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice. Am J Physiol Endocrinol Metab 310: E346 -E354, 2016. First published December 29, 2015; doi:10.1152/ajpendo.00485.2015.-It has been proposed that diet-induced obesity at thermoneutrality (TN; 29°C) is reduced by a UCP1-dependent thermogenesis; however, it has not been shown how UCP1-dependent thermogenesis can be activated in the absence of sympathetic activity. A recent study provides such a mechanism by showing that dietary bile acids (BAs) suppress obesity in mice fed a high-fat diet (HFD) by a mechanism dependent on type 2 deiodinase (DIO2); however, neither a role for UCP1 nor the influence of sympathetic activity was properly assessed. To test whether the effects of BAs on adiposity are independent of Ucp1 and cold-activated thermogenesis, obesity phenotypes were determined in C57BL6/J. ϩ / ϩ (WT) and C57BL6/J.Ucp1. Ϫ / Ϫ mice (Ucp1-KO) housed at TN and fed a HFD with or without 0.5% (wt/wt) cholic acid (CA) for 9 wk. CA in a HFD reduced adiposity and hepatic lipogenesis and improved glucose tolerance in WT but not in Ucp1-KO mice and was accompanied by increases in food intake and energy expenditure (EE). In iBAT, CA increased Ucp1 mRNA and protein levels 1.5-and twofold, respectively, and increased DIO2 and TGR5 protein levels in WT mice. Despite enhanced Dio2 expression in Ucp1-KO and Ucp1-KO-CA treated mice, this did not enhance the ability of BAs to reduce obesity. By comparing the effects of BAs on WT and Ucp1-KO mice at TN, our study showed that BAs suppress diet-induced obesity by increasing EE through a mechanism dependent on Ucp1 expression, which is likely independent of adrenergic signaling.brown adipose tissue; diet-induced obesity; mitochondrial uncoupling protein 1; bile acids; thermogenesis; type 2 deidodinase IN MICE, A MAJOR MECHANISM for maintaining body temperature in a cold environment involves induction of uncoupling protein 1 (UCP1)-dependent thermogenesis in brown adipose tissue (BAT) (7). The consequence of this increase in energy expenditure (EE) is increased oxidation of lipid stores in the body with overall reductions in adipose tissue fat stores. Most of this enhanced thermogenesis in the cold is mediated by sympathetically activated thermogenesis by BAT (4), (10). It has been reported that dietary bile acids (BAs) suppress the development of diet-induced obesity by a mechanism in which BAs activate the type 2 deiodinase (DIO2) pathway through the G-coupled receptor TGR5 (GPR131 or GpBAR1; a G protein-coupled plasma membrane receptor for BAs) (27). DIO2 was implicated in the mechanism through the use of Dio2-KO (Dio2-knockout) mice, which were resistant to the weight-reducing effects of BAs (27). However, since the expression of Ucp1 in the Dio2-KO mouse is nearly normal, consistent with the observation that the Dio2-KO mice show only a slight sensitivity to cold exposure (8, 9), and the study was conducted at an undefined ambient temp...

show abstract

Section: E349contrasting

confidence: 41%

Section: E349mentioning

confidence: 99%

Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice

Ziętak

Kozak

2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…Elevated concentrations of cAMP activate type 2 deiodinase (D2), which converts the inactive thyroid hormone thyroxine to active 3-5-3 0 -triiodothyronine, thereby resulting in increased BAT activity and enhanced energy expenditure in murine BAT and human skeletal muscle (Watanabe et al, 2006). Indeed, the primary BA cholic acid increases whole-body energy expenditure in mice (Teodoro et al, 2014;Watanabe et al, 2006). Also in humans, an effect of BAs on energy expenditure has been proposed.…”

Section: Introductionmentioning

confidence: 96%

The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

et al. 2015

View full text Add to dashboard Cite

The interest in brown adipose tissue (BAT) as a target to combat metabolic disease has recently been renewed with the discovery of functional BAT in humans. In rodents, BAT can be activated by bile acids, which activate type 2 iodothyronine deiodinase (D2) in BAT via the G-coupled protein receptor TGR5, resulting in increased oxygen consumption and energy expenditure. Here we examined the effects of oral supplementation of the bile acid chenodeoxycholic acid (CDCA) on human BAT activity. Treatment of 12 healthy female subjects with CDCA for 2 days resulted in increased BAT activity. Whole-body energy expenditure was also increased upon CDCA treatment. In vitro treatment of primary human brown adipocytes derived with CDCA or specific TGR5 agonists increased mitochondrial uncoupling and D2 expression, an effect that was absent in human primary white adipocytes. These findings identify bile acids as a target to activate BAT in humans.

show abstract

“…In both rodents and humans, BAT is targeted by bile acids. In C57BL/6 mice, dietary supplementation with cholic acid increased the thermogenetic capacity of BAT even in a thermoneutral environment and prevented diet-induced obesity (Teodoro et al, 2014;Watanabe et al, 2006;Zietak and Kozak, 2016). Mechanistically, the binding of bile acids to the TGR5 receptor increased the intracellular concentrations of the second messenger cAMP, which activates expression of the gene encoding for type 2 deiodinase (DIO2).…”

Section: Bile Acidsmentioning

confidence: 99%

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Braun

Oeckl

Westermeier

et al. 2018

Journal of Experimental Biology

View full text Add to dashboard Cite

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.

show abstract

Enhancement of brown fat thermogenesis using chenodeoxycholic acid in mice

Cited by 63 publications

References 40 publications

Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice

Bile acids induce uncoupling protein 1-dependent thermogenesis and stimulate energy expenditure at thermoneutrality in mice

The Bile Acid Chenodeoxycholic Acid Increases Human Brown Adipose Tissue Activity

Non-adrenergic control of lipolysis and thermogenesis in adipose tissues

Contact Info

Product

Resources

About