Caloric restriction mimetics (CRMs) are nontoxic macroautophagy/autophagy enhancers that act through the stimulation of cytoplasmic protein deacetylation reactions. Thus far, three functional classes of CRMs have been described: inhibitors of acetyltransferases (such as spermidine), inhibitors of acetyl coenzyme (AcCoA) synthesis (such as hydroxycitrate) and activators of deacetylases/sirtuins (such as resveratrol). Triethylenetetramine (also called trientine, abbreviated TETA) is a synthetic polyamine with resemblance in its structure to spermidine, a natural polyamine reputed for its pro-autophagic, anti-obesity and anti-aging effects. TETA, which is approved for the treatment of Wilson disease, has no effects on the longevity of mice, yet does induce autophagy and reduces weight gain in mice fed a high-fat diet (HFD). Mechanistically, these effects of TETA involve an increased activity of the TETA-metabolizing enzyme, SAT1 (spermidine/spermine N1-acetyltransferase 1). SAT1 overactivation ultimately results in the depletion of intracellular AcCoA with a consequent de-acetylation of cytoplasmic proteins and induction of autophagy. Accordingly, TETA fails to induce autophagy or to control HFD-induced weight gain in SAT1-deficient mice. Altogether, these findings indicate that TETA induces autophagy through a novel mode of action, namely, by the activation of an AcCoA-depleting enzyme.

卡路里限制模拟物（CRM）是无毒的巨自噬/自噬增强剂，可通过刺激细胞质蛋白脱乙酰基反应来发挥作用。迄今为止，已描述了CRM的三种功能类别：乙酰基转移酶的抑制剂（如亚精胺），乙酰辅酶（AcCoA）合成的抑制剂（如羟柠檬酸）和脱乙酰基酶/沉默调节蛋白的活化剂（如白藜芦醇）。三亚乙基四胺（也称为trientine，缩写为TETA）是一种合成的多胺，其结构类似于亚精胺，亚精胺是一种天然的多胺，因其具有自噬，抗肥胖和抗衰老作用而闻名。已批准用于治疗威尔逊病的TETA对小鼠的寿命没有影响，但确实会诱导自噬并降低高脂饮食（HFD）喂养的小鼠的体重增加。机械上，TETA的这些作用涉及TETA代谢酶SAT1（亚精胺/亚精胺N1-乙酰基转移酶1）的活性增加。SAT1过度激活最终导致细胞内AcCoA耗竭，进而使胞质蛋白脱乙酰化并诱导自噬。因此，TETA不能在SAT1缺陷小鼠中诱导自噬或控制HFD诱导的体重增加。总而言之，这些发现表明TETA通过一种新的作用方式，即通过激活AcCoA消耗酶来诱导自噬。TETA不能在SAT1缺陷小鼠中诱导自噬或控制HFD诱导的体重增加。总而言之，这些发现表明TETA通过一种新的作用方式，即通过激活AcCoA消耗酶来诱导自噬。TETA不能在SAT1缺陷小鼠中诱导自噬或控制HFD诱导的体重增加。总而言之，这些发现表明TETA通过一种新的作用方式，即通过消耗AcCoA的酶的活化来诱导自噬。