Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.

Adipocyte pyruvate dehydrogenase kinase 4 expression is associated with augmented PPARγ upregulation in early-life programming of later obesity.
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DOI:
10.1016/j.fob.2012.02.003
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发表时间:
2012
期刊:
影响因子:
2.6
通讯作者:
Sugden MC
Sugden MC
中科院分区:
生物学4区
文献类型:
--
作者:
Holness MJ;Zariwala G;Walker CG;Sugden MC

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一种增加肥胖风险的早期饮食干预增强了脂肪细胞Pdk 4表达。腺苷增加脂肪细胞PDK 4表达。早期饮食干预增加了PPARγ表达并增强了脂解刺激。增强的脂解作用可通过提供PPARγ配体来增强脂肪细胞的PDK 4。我们研究了脂肪细胞从8周龄的控制大鼠后代(CON)或大鼠后代受到母亲的低(8%)蛋白质(MLP)喂养在怀孕/哺乳期,一个程序诱发肥胖。急性暴露于异丙肾上腺素或腺苷可增强CON和MLP脂肪细胞中PDK 4和PPARγ mRNA的表达。脂肪细胞Pdk 4表达增强与PPARγ表达增加相关。在MLP脂肪细胞中观察到较高水平的PDK 4和PPARγ。SCD 1是一个PPARγ靶点。异丙肾上腺素平行增强脂肪细胞PDK 4和SCD 1基因表达。这可能反映了增强的PPARγ表达以及增强的脂解刺激以提供内源性PPARγ配体,从而通过PPARγ活化增强脂肪细胞PDK 4和SCD 1表达。相比之下,腺苷增加PDK 4表达的作用与脂解刺激无关,并且由于SCD 1表达不受腺苷影响,因此不太可能反映PPARγ激活。在MLP模型中,PDK 4和SCD 1的脂肪细胞表达增加可以作为“节俭”表型的组分参与,有利于肥胖的发展。
► An early-life dietary intervention increasing the risk of obesity enhances adipocyte Pdk4 expression. ► Adenosine increases adipocyte PDK4 expression. ► An early-life dietary intervention augments PPARγ expression and enhances lipolytic stimulation. ► Enhanced lipolysis could supply PPARγ ligands enhancing adipocyte PDK4 via PPARγ activation. We studied adipocytes from 8-week-old control rat offspring (CON) or rat offspring subjected to maternal low (8%) protein (MLP) feeding during pregnancy/lactation, a procedure predisposing to obesity. Acute exposure to isoproterenol or adenosine enhanced PDK4 and PPARγ mRNA gene expression in CON and MLP adipocytes. Enhanced adipocyte Pdk4 expression correlated with increased PPARγ expression. Higher levels of PDK4 and PPARγ were observed in MLP adipocytes. SCD1 is a PPARγ target. Isoproterenol enhanced adipocyte PDK4 and SCD1 gene expression in parallel. This could reflect augmented PPARγ expression together with enhanced lipolytic stimulation to supply endogenous PPARγ ligands, allowing enhanced adipocyte PDK4 and SCD1 expression via PPARγ activation. In contrast, the effect of adenosine to increase PDK4 expression is independent of stimulation of lipolysis and, as SCD1 expression was unaffected by adenosine, unlikely to reflect PPARγ activation. Increased adipocyte expression of both PDK4 and SCD1 in the MLP model could participate as components of a “thrifty” phenotype, favouring the development of obesity.
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