Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome.
Chronic stress, combined with a high-fat/high-sugar diet, shifts sympathetic signaling toward neuropeptide Y and leads to obesity and the metabolic syndrome.
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DOI：
10.1196/annals.1410.035
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发表时间：
2008-12
影响因子：
5.2
通讯作者：
Zukowska Z
中科院分区：
文献类型：
--
作者：
Kuo LE;Czarnecka M;Kitlinska JB;Tilan JU;Kvetnanský R;Zukowska Z
为了应对压力，有些人会减肥，而另一些人则会增重。这被认为是由于增加β-肾上腺素能激活，身体的主要脂肪燃烧机制，或增加摄入富含糖和脂肪的“安慰食品”。然而，单靠高脂肪、高糖（HFS）饮食不能解释肥胖的流行，而单靠慢性压力往往会降低小鼠的肥胖。在这里，我们讨论如何慢性压力，当结合HFS饮食，导致腹部肥胖释放交感神经递质，神经肽Y（NPY），直接进入脂肪组织。在体外，当用地塞米松“应激”时，交感神经元转向表达更多的NPY，其通过激活相同的NPY-Y2受体（Y2 Rs）来刺激内皮细胞（血管生成）和前脂肪细胞增殖、分化和脂质填充（脂肪生成）。在体内，慢性应激，包括冷水或HFS喂养的小鼠的攻击，刺激内脏脂肪中NPY的释放和Y2 Rs的表达，在2周内增加其生长50%。3个月后，这导致代谢综合征样症状，包括腹部肥胖、炎症、高脂血症、高胰岛素血症、葡萄糖耐受不良、肝脂肪变性和高血压。值得注意的是，局部脂肪内Y2 R抑制或通过腺病毒Y2 R敲低逆转或预防脂肪积累和代谢并发症。这些研究首次证明，慢性应激通过NPY-Y2 R途径放大和加速饮食诱导的肥胖和代谢综合征。我们的研究结果还表明，在其他临床应用中，局部施用Y2 R拮抗剂用于治疗肥胖症和NPY-Y2激动剂用于增脂。
In response to stress, some people lose while others gain weight. This is believed to be due to either increased β-adrenergic activation, the body’s main fat-burning mechanism, or increased intake of sugar- and fat-rich “comfort foods.” A high-fat, high-sugar (HFS) diet alone, however, cannot account for the epidemic of obesity, and chronic stress alone tends to lower adiposity in mice. Here we discuss how chronic stress, when combined with an HFS diet, leads to abdominal obesity by releasing a sympathetic neurotransmitter, neuropeptide Y (NPY), directly into the adipose tissue. In vitro, when “stressed” with dexamethasone, sympathetic neurons shift toward expressing more NPY, which stimulates endothelial cell (angiogenesis) and preadipocyte proliferation, differentiation, and lipid-filling (adipogenesis) by activating the same NPY-Y2 receptors (Y2Rs). In vivo, chronic stress, consisting of cold water or aggression in HFS-fed mice, stimulates the release of NPY and the expression of Y2Rs in visceral fat, increasing its growth by 50% in 2 weeks. After 3 months, this results in metabolic syndrome-like symptoms with abdominal obesity, inflammation, hyperlipidemia, hyperinsulinemia, glucose intolerance, hepatic steatosis, and hypertension. Remarkably, local intra-fat Y2R inhibition pharmacologically or via adenoviral Y2R knock-down reverses or prevents fat accumulation and metabolic complications. These studies demonstrated for the first time that chronic stress, via the NPY-Y2R pathway, amplifies and accelerates diet-induced obesity and the metabolic syndrome. Our findings also suggest the use of local administration of Y2R antagonists for treatment of obesity and NPY-Y2 agonists for fat augmentation in other clinical applications.
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影响因子：
2.3
作者：
ZukowskaGrojec, Z
通讯作者：
ZukowskaGrojec, Z
影响因子：
5.3
作者：
Karvonen, MK;Valkonen, VP;Salonen, JT
通讯作者：
Salonen, JT
DOI：
10.1161/01.atv.0000071349.30914.25
发表时间：
2003-07-01
影响因子：
8.7
作者：
Li, LJ;Lee, EW;Zukowska, Z
通讯作者：
Zukowska, Z
影响因子：
4.8
作者：
Mashiko, S;Ishihara, A;Kanatani, A
通讯作者：
Kanatani, A
影响因子：
15.9
作者：
Lee, EW;Michalkiewicz, M;Zukowska, Z
通讯作者：
Zukowska, Z