短期高脂肪高糖饮食大鼠下丘脑弓状核和中脑边缘系统基因表达水平受中枢瘦素的差异调节。
Differential modulation of arcuate nucleus and mesolimbic gene expression levels by central leptin in rats on short-term high-fat high-sugar diet.
机构信息
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands.
Department of Endocrinology and Metabolism, Academic Medical Center, University of Amsterdam, Amsterdam, The Netherlands ; Hypothalamic Integration Mechanisms, Netherlands Institute for Neuroscience, Amsterdam, The Netherlands.
出版信息
PLoS One. 2014 Jan 31;9(1):e87729. doi: 10.1371/journal.pone.0087729. eCollection 2014.
OBJECTIVE
Leptin resistance is a common hallmark of obesity. Rats on a free-choice high-fat high-sugar (fcHFHS) diet are resistant to peripherally administered leptin. The aim of this study was to investigate feeding responses to central leptin as well as the associated changes in mRNA levels in hypothalamic and mesolimbic brain areas.
DESIGN AND METHODS
Rats on a CHOW or fcHFHS diet for 8 days received leptin or vehicle intracerebro(lateral)ventricularly (ICV) and food intake was measured 5 h and 24 h later. Four days later, rats were sacrificed after ICV leptin or vehicle and mRNA levels were quantified for hypothalamic pro-opiomelanocortin (POMC) and neuropeptide Y (NPY) and for preproenkephalin (ppENK) in nucleus accumbens and tyrosine hydroxylase (TH) in ventral tegmental area (VTA).
RESULTS
ICV leptin decreased caloric intake both in CHOW and fcHFHS rats. In fcHFHS, leptin preferentially decreased chow and fat intake. Leptin increased POMC and decreased NPY mRNA in CHOW, but not in fcHFHS rats. In CHOW rats, leptin had no effect on ppENK mRNA and decreased TH mRNA. In fcHFHS, leptin decreased ppENK mRNA and increased TH mRNA.
CONCLUSION
Despite peripheral and arcuate leptin resistance, central leptin suppresses feeding in fcHFHS rats. As the VTA and nucleus accumbens are still responsive to leptin, these brain areas may therefore, at least partly, account for the leptin-induced feeding suppression in rats on a fcHFHS diet.
目的
瘦素抵抗是肥胖的常见标志。随意选择高脂肪高糖（fcHFHS）饮食的大鼠对外周给予的瘦素有抵抗作用。本研究旨在研究中枢瘦素的摄食反应以及下丘脑和中脑边缘脑区相关 mRNA 水平的变化。
设计和方法
接受 CHOW 或 fcHFHS 饮食 8 天的大鼠接受侧脑室（ICV）给予瘦素或载体，5 小时和 24 小时后测量食物摄入量。四天后，大鼠在 ICV 给予瘦素或载体后处死，并定量测定下丘脑前阿黑皮素原（POMC）和神经肽 Y（NPY）以及伏隔核前原啡肽（ppENK）和腹侧被盖区酪氨酸羟化酶（TH）的 mRNA 水平。
结果
ICV 瘦素降低了 CHOW 和 fcHFHS 大鼠的热量摄入。在 fcHFHS 中，瘦素优先降低了饲料和脂肪的摄入量。瘦素增加了 CHOW 大鼠的 POMC 并降低了 NPY mRNA，但对 fcHFHS 大鼠没有影响。在 CHOW 大鼠中，瘦素对 ppENK mRNA 没有影响，但降低了 TH mRNA。在 fcHFHS 中，瘦素降低了 ppENK mRNA 并增加了 TH mRNA。
结论
尽管存在外周和弓状核瘦素抵抗，但中枢瘦素仍能抑制 fcHFHS 大鼠的摄食。由于 VTA 和伏隔核对瘦素仍有反应，因此这些脑区至少部分解释了 fcHFHS 饮食大鼠中瘦素诱导的摄食抑制。
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