Nøhr Mark K, Bobba Natalia, Richelsen Bjørn, Lund Sten, Pedersen Steen B
Institute of Clinical Medicine, Aarhus University, 8000 Aarhus C, Denmark.
Department of Endocrinology and Internal Medicine, Aarhus University Hospital, 8000 Aarhus C, Denmark.
Int J Mol Sci. 2017 May 8;18(5):1006. doi: 10.3390/ijms18051006.
Brown adipose tissue thermogenesis at the cost of energy is not only important for the development of obesity, but also possesses great promise in anti-obesity treatment. Uncoupling protein 1 (UCP1) expression has been reported to be under control of the intracellular deacetylase SIRT1. Here, we investigated the effect and mechanism of inflammation and sirtuin-1 (SIRT1) activation on the induction of thermogenic genes in immortalized brown adipocytes incubated with LPS or IL1β and mice with elevated inflammatory tone. In vitro stimulation of brown adipocytes with dibutyryl cyclic adenosine monophosthate (dbcAMP) reduced the expression of () (SIRT1 inhibitor) and increased the expression. Silencing of SIRT1 attenuated dbcAMP induction of . In contrast, IL1β increased the expression of and greatly reduced the induction of . Similarly, in vivo studies revealed decreased expression of in brown adipose tissue (BAT) in mice chronically infused with LPS. Resveratrol, a known SIRT1 activator, partly rescued the downregulation by inflammation in both the cell cultures and mice. Here, we describe how the expression of in BAT is controlled via SIRT1 and is reduced under inflammation and can be rescued by SIRT1 activation by resveratrol. We suggest the reduced UCP1 expression under inflammation is mediated by the increased expression of DBC1, which inhibits SIRT1 activity.
以能量为代价的棕色脂肪组织产热不仅对肥胖的发展很重要，而且在抗肥胖治疗中也具有巨大潜力。据报道，解偶联蛋白1（UCP1）的表达受细胞内脱乙酰酶SIRT1的控制。在此，我们研究了炎症和沉默调节蛋白1（SIRT1）激活对用脂多糖（LPS）或白细胞介素1β（IL1β）孵育的永生化棕色脂肪细胞以及炎症状态升高的小鼠中热生成基因诱导的影响和机制。用二丁酰环磷酸腺苷（dbcAMP）体外刺激棕色脂肪细胞可降低（）（SIRT1抑制剂）的表达并增加（）的表达。沉默SIRT1可减弱dbcAMP对（）的诱导。相反，IL1β增加了（）的表达并大大降低了对（）的诱导。同样，体内研究显示，长期输注LPS的小鼠棕色脂肪组织（BAT）中（）的表达降低。白藜芦醇是一种已知的SIRT1激活剂，在细胞培养和小鼠中均可部分挽救炎症导致的（）下调。在此，我们描述了BAT中（）的表达如何通过SIRT1控制，以及在炎症状态下如何降低，并且白藜芦醇激活SIRT1可使其得到挽救。我们认为炎症状态下UCP1表达降低是由DBC1表达增加介导的，DBC1可抑制SIRT1活性。
