Department of Metabolism and Aging, Scripps Research Institute, Jupiter, FL 33458, USA.
Physiol Behav. 2013 Oct 2;122:17-24. doi: 10.1016/j.physbeh.2013.07.014. Epub 2013 Aug 27.
Fatty acid metabolism is implicated in the hypothalamic control of food intake. In this regard, malonyl-CoA, an intermediate in fatty acid synthesis, is emerging as a key player. Malonyl-CoA in the hypothalamus has been proposed as an anorectic mediator in the central control of feeding. A large body of evidence demonstrates that modulating hypothalamic activities of malonyl-CoA metabolic enzymes impacts food intake. Malonyl-CoA action appears to play a significant role in the intracellular signaling pathways underlying leptin anorectic effect in the arcuate nucleus. Ghrelin's hypothalamic effect on feeding may also involve the change in malonyl-CoA metabolism. Hypothalamic malonyl-CoA levels are altered in response to fasting and refeeding, suggesting physiological relevance of the changes in malonyl-CoA level in the controls of feeding and energy balance. Malonyl-CoA inhibits the acyltransferase activity of carnitine palmitoyltransferase-1 (CPT-1), and CPT-1 was considered as a downstream effector in hypothalamic malonyl-CoA effect on feeding. However, recent evidence has not been entirely consistent with this notion. In the arcuate nucleus, the inhibition of CPT-1 acyltransferase activity does not play an important role in the feeding effect of either leptin or cerulenin (a fatty acid synthase inhibitor) that requires the increase in malonyl-CoA level. Alternatively, the brain isoform of CPT-1 (CPT-1c) may act as a downstream target in the malonyl-CoA signaling pathways. CPT-1c does not possess a typical acyltransferase activity, and the exact molecular function of this protein is currently unknown. Recent data indicate it is involved in ceramide metabolism. Of relevance, in the arcuate nucleus, CPT-1c may link malonyl-CoA to ceramide metabolism to affect food intake.
脂肪酸代谢参与了下丘脑对摄食的控制。在此方面，脂肪酸合成的中间产物丙二酰辅酶 A（malonyl-CoA）正成为一个关键的调控因子。已有研究提出，下丘脑的 malonyl-CoA 可能作为摄食中枢调控的一个厌食性介质。大量证据表明，调节下丘脑 malonyl-CoA 代谢酶的活性会影响摄食。malonyl-CoA 可能在瘦素抑制摄食的作用所涉及的细胞内信号通路中发挥重要作用。ghrelin 在下丘脑对摄食的影响也可能涉及到 malonyl-CoA 代谢的变化。禁食和再进食会改变下丘脑 malonyl-CoA 水平，这表明 malonyl-CoA 水平的变化在摄食和能量平衡的调控中具有生理意义。malonyl-CoA 抑制肉碱棕榈酰转移酶-1（CPT-1）的酰基转移酶活性，CPT-1 被认为是下丘脑 malonyl-CoA 对摄食作用的下游效应物。然而，最近的证据并不完全支持这一观点。在弓状核中，CPT-1 酰基转移酶活性的抑制在需要增加 malonyl-CoA 水平的瘦素或 cerulenin（脂肪酸合成酶抑制剂）的摄食效应中并不起重要作用。相反，CPT-1 的脑同工酶（CPT-1c）可能作为 malonyl-CoA 信号通路的下游靶标。CPT-1c 不具有典型的酰基转移酶活性，该蛋白的确切分子功能目前尚不清楚。最近的数据表明它参与了神经酰胺代谢。相关的是，在弓状核中，CPT-1c 可能将 malonyl-CoA 与神经酰胺代谢联系起来，从而影响摄食。
