Teodoro J S, Zouhar P, Flachs P, Bardova K, Janovska P, Gomes A P, Duarte F V, Varela A T, Rolo A P, Palmeira C M, Kopecký J
1] Center for Neuroscience and Cell Biology, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal [2] Department of Life Sciences, Faculty of Science and Technology, University of Coimbra, Coimbra, Portugal.
Department of Adipose Tissue Biology, Institute of Physiology Academy of Sciences of the Czech Republic v.v.i., Prague, Czech Republic.
Int J Obes (Lond). 2014 Aug;38(8):1027-34. doi: 10.1038/ijo.2013.230. Epub 2013 Dec 6.
Besides their role in lipid absorption, bile acids (BAs) can act as signalling molecules. Cholic acid was shown to counteract obesity and associated metabolic disorders in high-fat-diet (cHF)-fed mice while enhancing energy expenditure through induction of mitochondrial uncoupling protein 1 (UCP1) and activation of non-shivering thermogenesis in brown adipose tissue (BAT). In this study, the effects of another natural BA, chenodeoxycholic acid (CDCA), on dietary obesity, UCP1 in both interscapular BAT and in white adipose tissue (brite cells in WAT), were characterized in dietary-obese mice.
To induce obesity and associated metabolic disorders, male 2-month-old C57BL/6J mice were fed cHF (35% lipid wt wt(-1), mainly corn oil) for 4 months. Mice were then fed either (i) for 8 weeks with cHF or with cHF with two different doses (0.5%, 1%; wt wt(-1)) of CDCA (8-week reversion); or (ii) for 3 weeks with cHF or with cHF with 1% CDCA, or pair-fed (PF) to match calorie intake of the CDCA mice fed ad libitum; mice on standard chow diet were also used (3-week reversion).
In the 8-week reversion, the CDCA intervention resulted in a dose-dependent reduction of obesity, dyslipidaemia and glucose intolerance, which could be largely explained by a transient decrease in food intake. The 3-week reversion revealed mild CDCA-dependent and food intake-independent induction of UCP1-mediated thermogenesis in interscapular BAT, negligible increase of UCP1 in subcutaneous WAT and a shift from carbohydrate to lipid oxidation.
CDCA could reverse obesity in cHF-fed mice, mainly in response to the reduction in food intake, an effect probably occuring but neglected in previous studies using cholic acid. Nevertheless, CDCA-dependent and food intake-independent induction of UCP1 in BAT (but not in WAT) could contribute to the reduction in adiposity and to the stabilization of the lean phenotype.
除了在脂质吸收中发挥作用外，胆汁酸（BAs）还可作为信号分子。已证明胆酸可对抗高脂饮食（cHF）喂养小鼠的肥胖及相关代谢紊乱，同时通过诱导线粒体解偶联蛋白1（UCP1）和激活棕色脂肪组织（BAT）中的非寒战产热来增加能量消耗。在本研究中，在饮食性肥胖小鼠中研究了另一种天然胆汁酸——鹅去氧胆酸（CDCA）对饮食性肥胖、肩胛间BAT和白色脂肪组织（WAT中的米色细胞）中UCP1的影响。
为诱导肥胖及相关代谢紊乱，给2月龄雄性C57BL/6J小鼠喂食cHF（35%脂质重量/重量(-1)，主要为玉米油）4个月。然后将小鼠分为以下几组：（i）连续8周喂食cHF或添加两种不同剂量（0.5%、1%；重量/重量(-1)）CDCA的cHF（8周逆转期）；或（ii）连续3周喂食cHF或添加1% CDCA的cHF，或进行配对喂养（PF）以匹配自由采食的CDCA小鼠的卡路里摄入量；还使用了标准饲料喂养的小鼠（3周逆转期）。
在8周逆转期，CDCA干预导致肥胖、血脂异常和葡萄糖不耐受呈剂量依赖性降低，这在很大程度上可由食物摄入量的短暂减少来解释。3周逆转期显示，肩胛间BAT中UCP1介导的产热有轻度的CDCA依赖性且与食物摄入量无关的诱导，皮下WAT中UCP1增加可忽略不计，且代谢从碳水化合物氧化转变为脂质氧化。
CDCA可逆转cHF喂养小鼠的肥胖，主要是由于食物摄入量减少，这一效应在先前使用胆酸的研究中可能出现但被忽视。然而，BAT（而非WAT）中CDCA依赖性且与食物摄入量无关的UCP1诱导可能有助于降低肥胖程度并稳定瘦体型。
