Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Department of Physiology, CIMUS, University of Santiago de Compostela-Instituto de Investigación Sanitaria, Santiago de Compostela, 15782, Spain; CIBER Fisiopatología de la Obesidad y Nutrición (CIBERobn), 15706, Spain.
Redox Biol. 2021 May;41:101945. doi: 10.1016/j.redox.2021.101945. Epub 2021 Mar 13.
Sirtuin 3 (SIRT3) is one of the seven mammalian sirtuin homologs of the yeast Sir2 gene that has emerged as an important player in the regulation of energy metabolism in peripheral tissues. However, its role in the hypothalamus has not been explored. Herein, we show that the genetic inhibition of SIRT3 in the hypothalamic arcuate nucleus (ARC) induced a negative energy balance and improvement of several metabolic parameters. These effects are specific for POMC neurons, because ablation of SIRT3 in POMC, but not in AgRP neurons, decreased body weight and adiposity, increased energy expenditure and brown adipose tissue (BAT) activity, and induced browning in white adipose tissue (WAT). Notably, the depletion of SIRT3 in POMC neurons caused these effects in male mice fed a chow diet but failed to affect energy balance in males fed a high fat diet and females under both type of diets. Overall, we provide the first evidence pointing for a key role of SIRT3 in POMC neurons in the regulation of energy balance.
Sirtuin 3（SIRT3）是酵母 Sir2 基因的七种哺乳动物 Sirtuin 同源物之一，它已成为外周组织能量代谢调节的重要参与者。然而，它在下丘脑中的作用尚未得到探索。在此，我们发现抑制下丘脑弓状核（ARC）中的 SIRT3 会导致负性能量平衡和多种代谢参数的改善。这些作用是特异性针对 POMC 神经元的，因为 SIRT3 在 POMC 神经元中的缺失而非 AgRP 神经元中的缺失会降低体重和脂肪含量，增加能量消耗和棕色脂肪组织（BAT）活性，并诱导白色脂肪组织（WAT）的褐变。值得注意的是，POMC 神经元中 SIRT3 的耗竭会导致雄性小鼠在正常饮食喂养下出现这些效应，但在高脂肪饮食喂养的雄性和两种饮食喂养的雌性中，无法影响能量平衡。总体而言，我们提供了第一个证据，表明 SIRT3 在 POMC 神经元中在调节能量平衡方面发挥关键作用。
