Region-specific diet-induced and leptin-induced cellular leptin resistance includes the ventral tegmental area in rats.
Region-specific diet-induced and leptin-induced cellular leptin resistance includes the ventral tegmental area in rats.
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DOI：
10.1016/j.neuropharm.2010.11.002
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发表时间：
2011-02
影响因子：
4.7
通讯作者：
Scarpace, P. J.
中科院分区：
文献类型：
--
作者：
Matheny, M.;Shapiro, A.;Tuemer, N.;Scarpace, P. J.
饮食诱导的肥胖（DIO）导致一种小鼠下丘脑弓状核（ARC）和另一种小鼠下丘脑内侧基底区的区域特异性细胞瘦素抵抗。我们假设腹侧被盖区（VTA）也可能与下丘脑区平行地对饮食诱导和瘦素诱导的瘦素抵抗敏感。我们研究了两种形式的瘦素抵抗F344xBN大鼠，诱导6个月的高脂肪（HF）喂养和诱导15个月的中央瘦素过度表达通过使用重组腺相关病毒（rAAV）介导的基因传递大鼠瘦素。通过瘦素刺激下丘脑内侧基底区和腹侧被盖区信号转导子和转录激活子3（STAT3）的磷酸化来评估细胞瘦素抵抗。HF患者瘦素抵抗的区域模式和程度与瘦素过度表达患者明显不同。慢性HF喂养诱导的细胞瘦素抵抗，确定在ARC和VTA，但不存在于外侧下丘脑（LH），腹内侧下丘脑（VMH），和背内侧下丘脑（DMH）。相反，慢性中枢瘦素过度表达诱导细胞瘦素抵抗在所有领域的研究。除了下丘脑中的瘦素抵抗外，腹侧被盖区中的瘦素抵抗的鉴定提供了一种潜在的机制，该机制是瘦素抵抗大鼠对HF诱导的肥胖的易感性增加的基础。
Diet-induced obesity (DIO) results in region-specific cellular leptin resistance in the arcuate nucleus (ARC) of the hypothalamus in one strain of mice and in several medial basal hypothalamic regions in another. We hypothesized that the ventral tegmental area (VTA) is also likely susceptible to diet-induced and leptin-induced leptin resistance in parallel to that in hypothalamic areas. We examined two forms of leptin resistance in F344xBN rats, that induced by 6-months of high fat (HF) feeding and that induced by 15-months of central leptin overexpression by use of recombinant adeno-associated viral (rAAV)-mediated gene delivery of rat leptin. Cellular leptin resistance was assessed by leptin-stimulated phosphorylation of signal transducers and activators of transcription 3 (STAT3) in medial basal hypothalamic areas and the VTA. The regional pattern and degree of leptin resistance with HF was distinctly different than that with leptin overexpression. Chronic HF feeding induced a cellular leptin resistance that was identified in the ARC and VTA, but absent in the lateral hypothalamus (LH), ventromedial hypothalamus (VMH), and dorsomedial hypothalamus (DMH). In contrast, chronic central leptin overexpression induced cellular leptin resistance in all areas examined. The identification of leptin resistance in the VTA, in addition to the leptin resistance in the hypothalamus, provides one potential mechanism, underlying the increased susceptibility of leptin resistant rats to HF-induced obesity.
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影响因子：
4.7
作者：
Scarpace, PJ;Matheny, M;Zolotukhin, S
通讯作者：
Zolotukhin, S
DOI：
10.1152/ajpendo.90865.2008
发表时间：
2009-07-01
影响因子：
5.1
作者：
Morton, Gregory J.;Blevins, James E.;Figlewicz, Dianne P.
通讯作者：
Figlewicz, Dianne P.
影响因子：
3.3
作者：
Scarpace, PJ;Matheny, M;Tümer, N
通讯作者：
Tümer, N
DOI：
10.1152/ajpregu.90449.2008
发表时间：
2009-11-01
影响因子：
2.8
作者：
Matheny, Michael;Zhang, Yi;Scarpace, Philip J.
通讯作者：
Scarpace, Philip J.
影响因子：
4.8
作者：
Münzberg, H;Flier, JS;Bjorbæk, C
通讯作者：
Bjorbæk, C