Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK
Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK
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DOI：
10.1152/ajpcell.00547.2009
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发表时间：
2010-04-01
影响因子：
5.5
通讯作者：
Ceddia, Rolando B.
中科院分区：
文献类型：
--
作者：
Gaidhu, Mandeep P.;Anthony, Nicole M.;Ceddia, Rolando B.
Gaidhu MP、Anthony NM、Patel P、Hawke TJ、Ceddia RB。高脂饮食引起内脏和皮下脂肪细胞脂解和脂质代谢失调：ATGL、HSL和AMPK的作用美国生理学杂志细胞生理学298：C961-C971，2010年。首次发表于2010年1月27日; doi：10.1152/ajpcell.00547.2009。本研究探讨了高脂饮食（HFD）对小鼠附睾（内脏，VC）和腹股沟（皮下，SC）脂肪细胞脂解和脂质代谢失调的分子机制。八周的HFD喂养增加脂肪甘油三酯脂肪酶（ATGL）的含量和比较基因识别-58（CGI-58）的表达，而脂肪敏感脂肪酶（HSL）磷酸化和围脂蛋白含量严重减少。来自HFD小鼠的脂肪细胞引起增加的基础但钝化肾上腺素刺激的脂解和增加的二酰甘油含量在两个脂肪库。与受损的肾上腺素能受体信号传导一致，HFD还增加了两个脂肪库中脂肪特异性磷脂酶A2的表达。抑制E-前列腺素3受体增加基础脂解在控制脂肪细胞，但未能急性改变的影响，HFD对脂解在两个脂肪库。在HFD内脏脂肪细胞，腺苷酸环化酶的激活，毛喉素增加HSL磷酸化，并超过对照细胞的脂解反应。然而，在HFD皮下脂肪细胞，毛喉素诱导脂解没有可检测的HSL磷酸化，这表明在VC和SC脂肪细胞的HFD诱导的HSL抑制响应的替代脂肪酶的激活。HFD还能有效抑制基础、肾上腺素和毛喉素诱导的AMP激酶（AMPK）激活以及过氧化物酶体增殖物激活受体γ共激活因子-1 α表达、柠檬酸合酶活性和两种脂肪库中的棕榈酸氧化。总之，提供了新的证据，缺陷的肾上腺素能受体信号传导结合ATGL的上调和HSL和AMPK信号传导的抑制介导HFD诱导的VC和SC脂肪细胞中的脂解和脂质利用的改变，这可能在饮食诱导的肥胖中观察到的缺陷的脂质动员和代谢中起重要作用。
Gaidhu MP, Anthony NM, Patel P, Hawke TJ, Ceddia RB. Dysregulation of lipolysis and lipid metabolism in visceral and subcutaneous adipocytes by high-fat diet: role of ATGL, HSL, and AMPK. Am J Physiol Cell Physiol 298: C961-C971, 2010. First published January 27, 2010; doi:10.1152/ajpcell.00547.2009.-This study investigated the molecular mechanisms by which a high-fat diet (HFD) dysregulates lipolysis and lipid metabolism in mouse epididymal (visceral, VC) and inguinal (subcutaneous, SC) adipocytes. Eight-weeks of HFD feeding increased adipose triglyceride lipase (ATGL) content and comparative gene identification-58 (CGI-58) expression, whereas hormone-sensitive lipase (HSL) phosphorylation and perilipin content were severely reduced. Adipocytes from HFD mice elicited increased basal but blunted epinephrine-stimulated lipolysis and increased diacylglycerol content in both fat depots. Consistent with impaired adrenergic receptor signaling, HFD also increased adipose-specific phospholipase A2 expression in both fat depots. Inhibition of E-prostanoid 3 receptor increased basal lipolysis in control adipocytes but failed to acutely alter the effects of HFD on lipolysis in both fat depots. In HFD visceral adipocytes, activation of adenylyl cyclases by forskolin increased HSL phosphorylation and surpassed the lipolytic response of control cells. However, in HFD subcutaneous adipocytes, forskolin induced lipolysis without detectable HSL phosphorylation, suggesting activation of an alternative lipase in response to HFD-induced suppression of HSL in VC and SC adipocytes. HFD also powerfully inhibited basal, epinephrine-, and forskolin-induced AMP kinase (AMPK) activation as well peroxisome proliferator-activated receptor gamma coactivator-1 alpha expression, citrate synthase activity, and palmitate oxidation in both fat depots. In summary, novel evidence is provided that defective adrenergic receptor signaling combined with upregulation of ATGL and suppression of HSL and AMPK signaling mediate HFD-induced alterations in lipolysis and lipid utilization in VC and SC adipocytes, which may play an important role in defective lipid mobilization and metabolism seen in diet-induced obesity.