On the control of lipolysis in adipocytes
On the control of lipolysis in adipocytes
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DOI：
10.1111/j.1749-6632.1999.tb07794.x
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发表时间：
1999-01-01
期刊：
影响因子：
--
通讯作者：
Rondinone, CM
中科院分区：
文献类型：
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作者：
Londos, C;Brasaemle, DL;Rondinone, CM
脂肪细胞中的脂肪分解反应是身体能量储备管理中最重要的反应之一，这种反应的失调可能会导致 2 型糖尿病的症状。然而，保留该反应分子细节的进展相对缓慢。然而，分子水平上的最新进展开始描绘出更清晰的脂肪分解图景，并指出了许多尚未解答的问题。虽然 HSL 长期以来被认为是脂肪分解的限速酶，但 HSL 攻击液滴脂质的机制尚未确定。当然，免疫细胞化学证据显示，刺激后 HSL 向脂滴移动，这一点毫无疑问，这种易位是脂肪分解反应的关键方面，但 HSL 磷酸化是否有助于易位，以及在哪个位点，尚未解决。确定除了易位反应之外是否还有激活步骤也很重要。研究结果表明，perilipin A 的参与可以保护液滴内的中性脂质免遭水解，但其对脂肪分解反应的积极参与尚未得到证实。同样，重要的是确定周脂肪素 PKA 磷酸化位点丝氨酸残基的突变是否会阻止脂肪分解，以及此类修饰是否消除了伴随脂肪分解的液滴表面的物理变化。
The lipolytic reaction in adipocytes is one of the most important reactions in the management of bodily energy reserves, and dysregulation of this reaction may contribute to the symptoms of Type 2 diabetes mellitus. Yet, progress on reserving the molecular details of this reaction has been relatively slow. However, recent developments at the molecular level begin to paint a clearer picture of lipolysis and point to a number of unanswered questions. While HSL has long been known to be the rate-limiting enzyme of lipolysis, the mechanism by which HSL attacks the droplet lipids is not yet firmly established. Certainly, the immunocytochemical evidence showing the movement of HSL to the lipid droplet upon stimulation leaves little doubt that this translocation is a key aspect of the lipolytic reaction, but whether or not HSL phosphorylation contributes to the translocation, and at which site(s), is as yet unresolved. It will be important to establish whether there is an activation step in addition to the translocation reaction. The participation of perilipin A is indicated by the findings that this protein can protect neutral lipids within droplets from hydrolysis, but active participation in the lipolytic reaction is yet to be proved. Again, it will be important to determine whether mutations of serine residues of PKA phosphorylation sites of perilipins prevent lipolysis, and whether such modifications abolish the physical changes in the droplet surfaces that accompany lipolysis.