Metabolomic analyses reveal that anti-aging metabolites are depleted by palmitate but increased by oleate in vivo
Metabolomic analyses reveal that anti-aging metabolites are depleted by palmitate but increased by oleate in vivo
复制标题
DOI：
10.1080/15384101.2015.1064206
复制
发表时间：
2015-08-03
期刊：
影响因子：
4.3
通讯作者：
Kroemer, Guido
中科院分区：
文献类型：
--
作者：
Enot, David P.;Niso-Santano, Mireia;Kroemer, Guido
最近，我们报道了饱和和不饱和脂肪酸通过不同的信号转导途径触发自噬。像棕榈酸酯(PA)这样的饱和脂肪酸通过磷脂酰肌醇3-激酶、催化亚单位3(PIK3C3，最广为人知的Vps34)和Beclin 1(BECN1)诱导自噬反应。相反，不饱和脂肪酸，如油酸(OL)，促进非标准的、PIK3C3和BECN1非依赖的自噬。在这里，我们探讨了自噬诱导剂量的PA和OL对小鼠的代谢影响。结合主成分分析的质谱仪显示，PA和OL引起循环代谢物以及肝脏、心脏和骨骼肌代谢谱的明显变化。重要的是，PA(而不是OL)会导致肝脏中多种自噬抑制氨基酸的耗尽。相反，OL(而不是PA)增加了肝脏中烟酰胺腺嘌呤二核苷酸(NAD)的水平，NAD是sirtuin家族自噬刺激酶的必备辅助因子。此外，PA(而不是OL)提高了心脏中酰肉碱的浓度，这一现象可能与其心脏毒性有关。PA还能耗尽肝脏中的精胺和亚精胺，两种多胺被认为具有延长生命的活性。不饱和脂肪酸和饱和脂肪酸造成的代谢变化可能分别有助于它们促进健康和恶化健康的效果。
Recently, we reported that saturated and unsaturated fatty acids trigger autophagy through distinct signal transduction pathways. Saturated fatty acids like palmitate (PA) induce autophagic responses that rely on phosphatidylinositol 3-kinase, catalytic subunit type 3 (PIK3C3, best known as VPS34) and beclin 1 (BECN1). Conversely, unsaturated fatty acids like oleate (OL) promote non-canonical, PIK3C3- and BECN1-independent autophagy. Here, we explored the metabolic effects of autophagy-inducing doses of PA and OL in mice. Mass spectrometry coupled to principal component analysis revealed that PA and OL induce well distinguishable changes in circulating metabolites as well as in the metabolic profile of the liver, heart, and skeletal muscle. Importantly, PA (but not OL) causes the depletion of multiple autophagy-inhibitory amino acids in the liver. Conversely, OL (but not PA) increased the hepatic levels of nicotinamide adenine dinucleotide (NAD), an obligate co-factor for autophagy-stimulatory enzymes of the sirtuin family. Moreover, PA (but not OL) raised the concentrations of acyl-carnitines in the heart, a phenomenon that perhaps is linked to its cardiotoxicity. PA also depleted the liver from spermine and spermidine, 2 polyamines have been ascribed with lifespan-extending activity. The metabolic changes imposed by unsaturated and saturated fatty acids may contribute to their health-promoting and health-deteriorating effects, respectively.