Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Department of Physiology and Biophysics, Institute of Biomedical Sciences, University of São Paulo, São Paulo, Brazil.
Life Sci. 2019 Sep 1;232:116683. doi: 10.1016/j.lfs.2019.116683. Epub 2019 Jul 22.
Previous work has demonstrated that ketogenic diets promote white fat browning; however, the exact mechanisms underlying this phenomenom have yet to be elucidated. Recently, an in vitro study showed that supraphysiological concentrations of β-hydroxybutyrate (βHB) had a strong influence on the induction of adipocyte browning. On the other hand, concentrations in the physiological range, achieved through ketogenic diets and prolonged fasting produce values of 1-3 mM and 4-7 mM, respectively. Herein, we investigated the impact of physiological concentrations of βHB on metabolism, and the expression of uncoupling protein 1 (UCP1) and other browning markers in adipose tissues.
The effects of βHB on adipocyte browning were investigated in vitro, using primary cultures of isolated visceral and subcutaneous fat cells and cultured 3T3-L1 adipocytes, and in vivo.
It was determined that βHB failed to induce changes in the oxidative capacity, citrate synthase activity or browning gene expression patterns in isolated adipocytes, and did not exert a permissive effect on β-adrenergic agonist-induced browning. In addition, 3T3-L1 adipocytes differentiated following βHB treatment exhibited downregulated Ucp1 expression levels, a result that was recapitulated in the subcutaneous adipose tissue of Wistar rats after βHB salt treatment. Rats administered βHB salts also presented reduced brown adipose tissue UCP1 protein expression.
The mechanisms underlying ketogenic diet-induced browning of adipocytes are not known. The results from the present study indicate that physiological concentrations of βHB are not responsible for this phenomenon, despite the observed βHB-mediated downregulation of UCP1 expression.
先前的研究表明生酮饮食可促进白色脂肪棕色化；然而，其具体机制尚未阐明。最近的一项体外研究表明，超生理浓度的β-羟丁酸（βHB）对诱导脂肪细胞棕色化有很强的影响。另一方面，通过生酮饮食和长时间禁食达到的生理范围内的浓度分别产生 1-3mM 和 4-7mM 的βHB。在此，我们研究了生理浓度的βHB 对代谢以及脂肪组织中解偶联蛋白 1（UCP1）和其他棕色化标志物表达的影响。
使用分离的内脏和皮下脂肪细胞的原代培养物和培养的 3T3-L1 脂肪细胞以及体内实验，研究了βHB 对脂肪细胞棕色化的影响。
βHB 未能诱导分离的脂肪细胞氧化能力、柠檬酸合酶活性或棕色化基因表达模式发生变化，也未对β-肾上腺素能激动剂诱导的棕色化产生许可作用。此外，βHB 处理后分化的 3T3-L1 脂肪细胞表现出 Ucp1 表达水平下调，这一结果在 Wistar 大鼠经βHB 盐处理后的皮下脂肪组织中得到重现。βHB 盐给药的大鼠也表现出棕色脂肪组织 UCP1 蛋白表达减少。
生酮饮食诱导脂肪细胞棕色化的机制尚不清楚。本研究结果表明，尽管观察到βHB 介导的 UCP1 表达下调，但生理浓度的βHB 与这种现象无关。
